JP5704554B2 - Compounds that induce human stem cells to differentiate into hepatocytes - Google Patents
Compounds that induce human stem cells to differentiate into hepatocytes Download PDFInfo
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- JP5704554B2 JP5704554B2 JP2010092948A JP2010092948A JP5704554B2 JP 5704554 B2 JP5704554 B2 JP 5704554B2 JP 2010092948 A JP2010092948 A JP 2010092948A JP 2010092948 A JP2010092948 A JP 2010092948A JP 5704554 B2 JP5704554 B2 JP 5704554B2
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Description
本発明は、間葉系幹細胞の肝細胞への分化誘導剤、それを用いる肝細胞の生産方法、その生産方法による肝細胞、肝組織および肝臓に関する。 The present invention relates to an agent for inducing differentiation of mesenchymal stem cells into hepatocytes, a method for producing hepatocytes using the same, hepatocytes, liver tissue and liver by the production method.
肝臓病はわが国の国民病と言われ、多数の患者が肝臓病に苦しんでいる。また、肝細胞癌による年間死亡者数は約3万4千人に上る。最近では肝細胞癌は治療法の進歩により治療成績が向上しているが、進行癌の増加に伴い、合併する肝硬変の肝機能低下による、いわゆる肝不全死が増加している。肝不全治療は、肝移植が理想的であるが、わが国では十分なドナーを得ることは困難であり、幹細胞による肝再生治療の開発が必要である。 Liver disease is said to be a national disease in Japan, and many patients suffer from liver disease. The annual number of deaths from hepatocellular carcinoma is about 34,000. Recently, hepatocellular carcinoma has improved its therapeutic results due to advances in treatment, but with the increase of advanced cancer, so-called death of liver failure due to decreased liver function due to cirrhosis is increasing. Liver transplantation is ideal for liver failure treatment, but it is difficult to obtain sufficient donors in Japan, and it is necessary to develop liver regeneration treatment using stem cells.
肝細胞への分化する可能性のある幹細胞として、骨髄細胞、臍帯血細胞などの組織幹細胞が期待できる。そのため、多くの研究機関が、慢性肝不全患者への肝細胞移植治療による再生医療の実現のため、ヒト組織幹細胞を機能性肝細胞へ分化させる、真に臨床応用可能な効率的な分化誘導技術を開発することを目標に研究開発を行っている。 Tissue stem cells such as bone marrow cells and umbilical cord blood cells can be expected as stem cells that can differentiate into hepatocytes. For this reason, many research institutes are able to differentiate human tissue stem cells into functional hepatocytes for the realization of regenerative medicine by hepatocyte transplantation therapy for patients with chronic liver failure. Research and development with the goal of developing.
例えば、鳥取大学医学研究科の汐田教授の研究室では、ヒト間葉系幹細胞から肝細胞への分化誘導時にWnt/β−カテニン経路が抑制されており、この経路をRNA干渉により抑制すれば肝細胞へ分化することを報告している(非特許文献1および非特許文献3〜5)。また、他の研究機関でも同様の分野の研究が行われている(非特許文献2、特許文献1〜2)。 For example, in the laboratory of Prof. Hirota of Tottori University School of Medicine, the Wnt / β-catenin pathway is suppressed during differentiation induction from human mesenchymal stem cells to hepatocytes, and if this pathway is suppressed by RNA interference, the liver It has been reported to differentiate into cells (Non-patent document 1 and Non-patent documents 3 to 5). In addition, other research institutions are also conducting research in the same field (Non-patent Document 2, Patent Documents 1 and 2).
一方、最近、4,000種類以上の大規模化合物ライブラリーのスクリーニングから、Wnt/β−カテニン経路抑制性の低分子化合物5種類が同定されている(非特許文献6〜9)。 On the other hand, recently, five types of low molecular weight compounds that inhibit Wnt / β-catenin pathway have been identified from screening of 4,000 or more large-scale compound libraries (Non-Patent Documents 6 to 9).
しかしながら、上記文献記載の従来技術は、以下の点で改善の余地を有していた。
第一に、特許文献1〜2では、非肝幹細胞から幹細胞を誘導するための蛋白質について説明されているが、分化誘導剤として蛋白製剤を用いているため、安定性・安全性などの面でさらなる改善の余地があった。
However, the prior art described in the above literature has room for improvement in the following points.
First, Patent Documents 1 and 2 describe proteins for inducing stem cells from non-hepatic stem cells. However, since a protein preparation is used as a differentiation inducer, in terms of stability and safety, etc. There was room for further improvement.
第二に、非特許文献1および非特許文献3〜5では、ヒト間葉系幹細胞から肝細胞への分化誘導時にWnt/β−カテニン経路が抑制されており、この経路をRNA干渉により抑制すれば肝細胞へ分化することを報告しているが、分化誘導剤としてSiRNAを用いているため、同様に安定性・安全性などの面でさらなる改善の余地があった。 Secondly, in Non-Patent Document 1 and Non-Patent Documents 3 to 5, the Wnt / β-catenin pathway is suppressed during differentiation induction from human mesenchymal stem cells to hepatocytes, and this pathway is suppressed by RNA interference. However, since SiRNA is used as a differentiation inducer, there is still room for further improvement in terms of stability and safety.
第三に、非特許文献2では、ヘキサクロロフェンがWnt/β−カテニン経路を抑制するか検討しているが、ヘキサクロロフェンがヒト間葉系幹細胞から肝細胞への分化を誘導するか検討していない。そのため、非特許文献2を参照しても、ヘキサクロロフェンがヒト間葉系幹細胞から肝細胞への分化を誘導するかどうかについては不明である。 Third, Non-Patent Document 2 examines whether hexachlorophene suppresses the Wnt / β-catenin pathway, but examines whether hexachlorophene induces differentiation from human mesenchymal stem cells to hepatocytes. Absent. Therefore, even if Non-Patent Document 2 is referred to, it is unclear whether hexachlorophene induces differentiation from human mesenchymal stem cells to hepatocytes.
第四に、非特許文献6〜9では、5種類の低分子化合物がWnt/β−カテニン経路を抑制するか検討しているが、5種類の低分子化合物がヒト間葉系幹細胞から肝細胞への分化を誘導するか検討していない。そのため、非特許文献6〜9を参照しても、5種類の低分子化合物がヒト間葉系幹細胞から肝細胞への分化を誘導するかどうかについては不明である。 Fourthly, Non-Patent Documents 6 to 9 examine whether five kinds of low molecular weight compounds suppress the Wnt / β-catenin pathway, but five kinds of low molecular weight compounds are transformed from human mesenchymal stem cells to hepatocytes. We are not considering whether to induce differentiation. Therefore, it is unclear whether or not five low molecular weight compounds induce differentiation from human mesenchymal stem cells to hepatocytes even with reference to Non-Patent Documents 6 to 9.
本発明は上記事情に鑑みてなされたものであり、間葉系幹細胞から肝細胞への分化を誘導する有効な低分子化合物を選択し、間葉系幹細胞から肝細胞への分化効率に優れる安全な分化誘導法を開発することを目的とする。 The present invention has been made in view of the above circumstances, selects an effective low-molecular compound that induces differentiation from mesenchymal stem cells to hepatocytes, and is excellent in safety of differentiation from mesenchymal stem cells to hepatocytes. The purpose is to develop a different differentiation induction method.
本発明によれば、間葉系幹細胞の肝細胞への分化誘導剤であって、Wnt/β−カテニン経路を抑制する有機低分子量化合物を含む、分化誘導剤が提供される。 According to the present invention, there is provided a differentiation-inducing agent comprising a mesenchymal stem cell differentiation-inducing agent, which comprises an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway.
この構成によれば、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いるので、蛋白製剤や核酸製剤に比べ安定性・安全性などの面で優れており、間葉系幹細胞から肝細胞への分化効率に優れる安全な分化誘導法を実現できる。 According to this configuration, since an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway is used, it is superior in terms of stability and safety as compared with protein preparations and nucleic acid preparations. From mesenchymal stem cells to hepatocytes A safe differentiation induction method with excellent differentiation efficiency can be realized.
また、本発明によれば、間葉系幹細胞から肝細胞を生産する方法であって、間葉系幹細胞を上記の分化誘導剤で処理する工程を含む、生産方法が提供される。 The present invention also provides a method for producing hepatocytes from mesenchymal stem cells, comprising the step of treating mesenchymal stem cells with the above differentiation inducer.
この方法によれば、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いるので、蛋白製剤や核酸製剤に比べ安定性・安全性などの面で優れており、間葉系幹細胞から肝細胞への分化誘導を効率よく安全に行うことができる。 According to this method, since an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway is used, it is superior in terms of stability and safety as compared with protein preparations and nucleic acid preparations. From mesenchymal stem cells to hepatocytes Differentiation can be efficiently and safely performed.
また、本発明によれば、間葉系幹細胞から分化誘導された肝細胞であって、間葉系幹細胞を上記の分化誘導剤で処理してなる、肝細胞が提供される。 In addition, according to the present invention, there is provided a hepatocyte that has been induced to differentiate from mesenchymal stem cells, and is obtained by treating mesenchymal stem cells with the above-described differentiation inducer.
この幹細胞は、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いて間葉系幹細胞から分化誘導されるので、蛋白製剤や核酸製剤を用いて分化誘導される場合に比べ製造時の安定性・安全性などの面で優れている。 Since this stem cell is induced to differentiate from mesenchymal stem cells using an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway, it is more stable at the time of manufacture than when induced to differentiate using a protein preparation or a nucleic acid preparation. Excellent in terms of safety and safety.
また、本発明によれば、再生医療用の肝組織または肝臓であって、上記の肝細胞を含む肝組織または肝臓が提供される。 In addition, according to the present invention, there is provided a liver tissue or liver for regenerative medicine, which includes the aforementioned hepatocytes.
この肝組織または肝臓は、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いて間葉系幹細胞から分化誘導される幹細胞を用いるので、蛋白製剤や核酸製剤を用いて分化誘導される幹細胞を用いる場合に比べ製造時の安定性・安全性などの面で優れているため、再生医療用の肝組織または肝臓として好適に使用できる。 Since this liver tissue or liver uses stem cells that are induced to differentiate from mesenchymal stem cells using an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway, stem cells that are induced to differentiate using protein preparations or nucleic acid preparations. Since it is superior in terms of stability and safety at the time of manufacture as compared with the case of using, it can be suitably used as a liver tissue or liver for regenerative medicine.
本発明によれば、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いるので、蛋白製剤や核酸製剤に比べ安定性・安全性などの面で優れており、間葉系幹細胞から肝細胞への分化誘導を効率よく安全に行うことができる。 According to the present invention, since an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway is used, it is superior in terms of stability and safety as compared with protein preparations and nucleic acid preparations. From mesenchymal stem cells to hepatocytes Differentiation can be efficiently and safely performed.
以下、本発明の実施の形態について詳細に説明する。
<間葉系幹細胞の肝細胞への分化誘導剤>
本実施形態に係る間葉系幹細胞の肝細胞への分化誘導剤は、Wnt/β−カテニン経路を抑制する有機低分子量化合物を含む、分化誘導剤である。この構成によれば、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いるので、蛋白製剤や核酸製剤に比べ安定性・安全性などの面で優れており、間葉系幹細胞から肝細胞への分化効率に優れる安全な分化誘導法を実現できる。
Hereinafter, embodiments of the present invention will be described in detail.
<Induction agent for differentiation of mesenchymal stem cells into hepatocytes>
The agent for inducing differentiation of mesenchymal stem cells into hepatocytes according to this embodiment is a differentiation inducing agent containing an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway. According to this configuration, since an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway is used, it is superior in terms of stability and safety as compared with protein preparations and nucleic acid preparations. From mesenchymal stem cells to hepatocytes A safe differentiation induction method with excellent differentiation efficiency can be realized.
本明細書において、「間葉系幹細胞」(mesenchymal stem cell)とは、間葉に由来する体性幹細胞を含む。この間葉系幹細胞は、間葉系に属する細胞への分化能をもつ。この間葉系幹細胞は、近年の骨や血管、心筋の再構築などの再生医療への応用が期待されている。 In the present specification, “mesenchymal stem cell” includes somatic stem cells derived from mesenchyme. These mesenchymal stem cells have the ability to differentiate into cells belonging to the mesenchymal system. This mesenchymal stem cell is expected to be applied to regenerative medicine such as bone, blood vessel, and myocardial reconstruction in recent years.
「間葉系幹細胞」(mesenchymal stem cell)には、例えば、骨髄間葉系細胞および臍帯血由来幹細胞が含まれる。間葉系幹細胞は間葉系組織のあるすべての組織に存在すると考えられているが、間葉系組織のなかでも骨髄間葉系幹細胞は、骨髄穿刺で容易に採取でき、培養技術も確立されている。骨髄間葉系幹細胞は骨髄間質細胞の中に含まれており、骨髄間質細胞は骨髄の中で主体となる造血細胞を支える細胞の一種である。一方、臍帯血(さいたいけつ)とは、胎児と母体を繋ぐ胎児側の組織であるへその緒(臍帯;さいたい)の中に含まれる血液を含む。この臍帯血のなかには、臍帯血由来幹細胞(造血幹細胞)が多量に含まれていることが知られている。最近、造血幹細胞以外の体性幹細胞である間葉系幹細胞(臍帯血由来の間葉性幹細胞)が臍帯血中から見出されている。これまで間葉系幹細胞は骨髄中に存在することが報告されていたが、骨髄だけでなく臍帯血も間葉系幹細胞の供給源として、骨や軟骨の組織工学的修復あるいは再生医療への臨床応用へ適用できる可能性が示されている。ここで、間葉系幹細胞は一般にライフスパンが短く、in vitroでの長期培養は必ずしも容易ではないが、既にhTERT遺伝子などを導入し、安定に増殖しうるヒト骨髄由来およびヒト臍帯血由来間葉系幹細胞株が樹立されている。これらの細胞は、安定に増殖するが、染色体異常がなく、コンタクトインヒビションが機能し、免疫抑制動物に移植しても腫瘍を形成しない。また、細胞分化に影響しないことから、間葉系幹細胞の分化研究に有用な細胞である。 “Mesenchymal stem cells” include, for example, bone marrow mesenchymal cells and cord blood-derived stem cells. Although mesenchymal stem cells are thought to exist in all tissues with mesenchymal tissue, bone marrow mesenchymal stem cells can be easily collected by bone marrow puncture and culture techniques have been established. ing. Bone marrow mesenchymal stem cells are contained in bone marrow stromal cells, and bone marrow stromal cells are a type of cells that support hematopoietic cells, which are the main components in bone marrow. On the other hand, umbilical cord blood includes the blood contained in the umbilical cord (umbilical cord), which is a fetal tissue that connects the fetus and the mother. It is known that the cord blood contains a large amount of cord blood-derived stem cells (hematopoietic stem cells). Recently, mesenchymal stem cells (umbilical cord blood-derived mesenchymal stem cells) that are somatic stem cells other than hematopoietic stem cells have been found in umbilical cord blood. Until now, it was reported that mesenchymal stem cells exist in the bone marrow, but not only bone marrow but also umbilical cord blood is a source of mesenchymal stem cells, which is clinically applied to tissue engineering repair of bone and cartilage or regenerative medicine The potential for application is shown. Here, mesenchymal stem cells generally have a short life span and are not always easy to cultivate in vitro for a long time. However, human bone marrow-derived and human umbilical cord blood-derived mesenchymal cells that have already been introduced with hTERT gene or the like and can be stably proliferated A stem cell line has been established. These cells grow stably but have no chromosomal abnormalities, function contact inhibition, and do not form tumors when transplanted into immunosuppressed animals. Moreover, since it does not affect cell differentiation, it is a useful cell for mesenchymal stem cell differentiation studies.
また、本明細書において、「肝細胞」(Hepatocyte)とは、肝臓を構成する70−80%を構成する約20μm大の細胞を含む。肝細胞はタンパク質の合成と貯蔵、炭水化物の変換、コレステロール、胆汁酸、リン脂質の合成、並びに、内生および外生物質の解毒、変性、排出に関与する。また胆汁の生成と分泌を促進する働きも持つ。 Further, in this specification, “hepatocyte” includes approximately 20 μm-sized cells constituting 70-80% constituting the liver. Hepatocytes are involved in protein synthesis and storage, carbohydrate conversion, cholesterol, bile acid, phospholipid synthesis, and detoxification, degeneration and excretion of endogenous and exogenous substances. It also has the function of promoting the production and secretion of bile.
本明細書において、「分化」とは、多細胞生物において個々の細胞が構造機能的に変化することを含む。一般的に、多細胞生物の幹細胞から機能性細胞への分化は往々にして不可逆なケースが多い。これまでの知見では、間葉系幹細胞は、分化多能性(Multipotency)を持つとされており、分化可能な細胞系列が限定されているが、多様な細胞種へ分化可能な能力を指す。そのため、一般的に胚葉を超えた分化は行えないが、本実施形態に係る間葉系幹細胞の肝細胞への分化誘導剤は、間葉系幹細胞から肝細胞への胚葉を超えた分化を誘導する点に大きな技術的な特徴があると言える。 As used herein, “differentiation” includes the structural and functional changes of individual cells in a multicellular organism. In general, the differentiation of multicellular organisms from stem cells to functional cells is often irreversible. According to the knowledge so far, mesenchymal stem cells are said to have multipotency, and the cell line that can be differentiated is limited, but refers to the ability to differentiate into various cell types. Therefore, although differentiation beyond germ layers is generally not possible, the differentiation inducer of mesenchymal stem cells according to this embodiment to hepatocytes induces differentiation beyond mesodermal cells from mesenchymal stem cells to hepatocytes. This is a major technical feature.
一般的に、肝再生医療の細胞ソースとして、肝幹細胞を用いるのが自然であるが、肝幹細胞は劇症肝炎などの重症肝障害時にしか出現しないことから、実際の患者からの採取は現実性が低い。そこで、肝臓以外の組織幹細胞やiPS細胞が、肝再生医療の細胞ソースとなると考えられる。近年、間葉系幹細胞はin vitroの条件下で、ある程度の肝機能をもつ細胞に分化しうることが報告されている。すなわち、間葉系幹細胞に種々のサイトカインを添加し、約4週間培養し肝細胞様に分化したと報告されている。間葉系幹細胞は骨髄、腰帯血などに存在し、比較的採取が容易である。骨髄は自己細胞を用いることで免疫拒絶反応を回避できる利点がある。また、臍帯血は通常廃棄されるため、倫理的問題が少ないというメリットがある。以上より、間葉系幹細胞は肝再生医療の有望な細胞ソースといえる In general, it is natural to use hepatic stem cells as a cell source for liver regenerative medicine, but hepatic stem cells appear only during severe liver disorders such as fulminant hepatitis, so collection from actual patients is a reality. Is low. Thus, tissue stem cells and iPS cells other than the liver are considered to be a cell source for liver regenerative medicine. In recent years, it has been reported that mesenchymal stem cells can be differentiated into cells having a certain degree of liver function under in vitro conditions. That is, it is reported that various cytokines were added to mesenchymal stem cells and cultured for about 4 weeks to differentiate into hepatocytes. Mesenchymal stem cells are present in bone marrow, lumbar blood, etc., and are relatively easy to collect. Bone marrow has the advantage of avoiding immune rejection by using autologous cells. Moreover, since cord blood is usually discarded, there is an advantage that there are few ethical problems. Thus, mesenchymal stem cells are a promising cell source for liver regenerative medicine
本明細書において、「Wnt/β−カテニン経路」とは、脊椎動物および無脊椎動物の発生における細胞運命決定を調節している経路の一種を含む。Wntリガンドは分泌性の、Frizzled受容体に結合する糖タンパクであり、それによりシグナルカスケードを惹起し、結果として、APC/Axin/GSK−3β複合体から多機能性キナーゼ:GSK−3βを解離させる。Wntシグナルがない場合(オフ状態)は、転写共役因子であり、細胞間接着に必須のアダプター蛋白でもあるβ−カテニンが、APC/Axin/GSK−3β複合体による分解標的となる。CK1とGSK−3βの協調作用により適切にリン酸化されると、β−カテニンはユビキチン化され、β−TrCP/SKP 複合体を介してプロテオゾームでの分解を受ける。 As used herein, the “Wnt / β-catenin pathway” includes one type of pathway that regulates cell fate decisions in vertebrate and invertebrate development. The Wnt ligand is a secreted, glycoprotein that binds to the Frizzled receptor, thereby inducing a signal cascade and consequently dissociating the multifunctional kinase: GSK-3β from the APC / Axin / GSK-3β complex . When there is no Wnt signal (off state), β-catenin, which is a transcription coupling factor and an adapter protein essential for cell-cell adhesion, becomes a degradation target by the APC / Axin / GSK-3β complex. When appropriately phosphorylated by the cooperative action of CK1 and GSK-3β, β-catenin is ubiquitinated and undergoes proteosomal degradation via the β-TrCP / SKP complex.
Wntが結合した場合(オン状態)は、Dishevelled(Dsh)が、一見、少なくとも部分的にはリン酸化されることで活性化し、次いで、分解誘導複合体からGSK−3βを引き離す。これが、β−カテニンレベルを安定、核内輸送、さらにはLEF/TCFのDNA結合因子へのリクルートメントを促し、そこで、β−カテニンはGriucho−HDAC補助抑制因子と置き換わり、転写活性化因子として作用する。 When Wnt binds (on state), the Dishwelled (Dsh) appears to be at least partially phosphorylated to activate, and then pulls GSK-3β away from the degradation-inducing complex. This stabilizes β-catenin levels, facilitates nuclear transport, and also recruits LEF / TCF to DNA binding factors, where β-catenin replaces the Griucho-HDAC co-suppressor and acts as a transcriptional activator. To do.
さらには、ホメオドメイン因子であるProp1との複合体において、β−カテニンは、転写抑制複合体と同様に状況依存的な活性化により作用することが示されている。重要なのは、いくつかのヒトの癌では、β−カテニンに、制御不能の安定化につながる点変異が見つかり、また、APCとaxinにおいても同様に変異が報告され、この経路の異常な活性化とヒト腫瘍との関連性が強調されていることである。発生過程において、Wnt/β−カテニン経路は、多くの異なる細胞種や組織において、レチノイン酸、FGF、TGF−β、BMPなどの多様な経路からのシグナルを統合する役目を担う。さらに、Wnt/β−カテニン経路の構成単位であるGSK−3βは、グリコーゲン代謝や他の主要な経路においても関連しており、それを阻害することが糖尿病や神経変性疾患には妥当な対処法とされる。 Furthermore, it has been shown that in a complex with Prop1, which is a homeodomain factor, β-catenin acts by context-dependent activation in the same manner as the transcription repression complex. Importantly, in some human cancers, point mutations have been found in β-catenin that lead to uncontrolled stabilization, and mutations have been reported in APC and axin as well, leading to abnormal activation of this pathway. The relevance to human tumors is emphasized. During development, the Wnt / β-catenin pathway is responsible for integrating signals from various pathways such as retinoic acid, FGF, TGF-β, and BMP in many different cell types and tissues. Furthermore, GSK-3β, which is a constituent unit of the Wnt / β-catenin pathway, is also associated with glycogen metabolism and other major pathways, and its inhibition is a reasonable countermeasure for diabetes and neurodegenerative diseases. It is said.
本明細書において、「低分子量有機化合物」(low molecular weight organic compound)とは、分子量2000以下の有機化合物を含む。好ましくは、この分子量は1000以下であり、特に好ましくは900以下であり、最も好ましくは800以下である。なぜなら、いわゆる核酸製剤、蛋白製剤を含む高分子は生体内外で分解されやすいため不安定であり、再生医療に活用する上では安全性の面でも不安が残る。これに対して、低分子量有機化合物は、生体内外で分解されにくいため安定であり、再生医療に活用する上では安全性の面でも有利である。また、分子量が小さいほど有機合成も容易であり、安定性、安全性などのフィージビリティにおいて優れている。なお、繰り返しになるが、この低分子量有機化合物からは、ペプチドおよびヌクレオチドが除かれる。なぜなら、ペプチドおよびヌクレオチドは、生体内外で分解されやすいため不安定であり、再生医療に活用する上では安全性の面でも不安が残るからである。 In the present specification, “low molecular weight organic compound” includes an organic compound having a molecular weight of 2000 or less. Preferably, this molecular weight is 1000 or less, particularly preferably 900 or less, and most preferably 800 or less. This is because macromolecules including so-called nucleic acid preparations and protein preparations are unstable because they are easily decomposed inside and outside the living body, and there are concerns about safety when they are used in regenerative medicine. In contrast, low molecular weight organic compounds are stable because they are difficult to be decomposed inside and outside the living body, and are advantageous in terms of safety when used in regenerative medicine. In addition, the smaller the molecular weight, the easier the organic synthesis and the better feasibility such as stability and safety. Again, peptides and nucleotides are excluded from this low molecular weight organic compound. This is because peptides and nucleotides are unstable because they are easily decomposed inside and outside the living body, and are uneasy in terms of safety when used in regenerative medicine.
そのため、本発明者らは、(1)現在市販されている4種類のWnt/βeta−catenin経路抑制剤(ケルセチン、イオノマイシン、イマチニブ、ヘキサクロロフェン)を入手し、さらに(2)その他の5種類のWnt/βeta−catenin経路抑制性の低分子化合物NSC668036、PKF−115−584、CPG049090、PNU−74654、ICG−001を合成して、肝細胞分化誘導作用を検討することとし、ヒト骨髄由来細胞(UE7T−13細胞)、ヒト臍帯血由来細胞(UCBTERT−21細胞)を用いて、上記の効果を以下の点について、検討した結果、後述する実施例で実証するように、これらのうちの4種類のWnt/βeta−catenin経路抑制剤(ケルセチン、イオノマイシン、ヘキサクロロフェン、PKF115−584)が間葉系幹細胞を幹細胞に分化誘導することを発見したものである。
1.肝特異的転写因子発現
2.肝特異的蛋白発現
3.グリコーゲン合成
4.尿素合成
5.TCF活性によるWnt/βeta−catenin経路のシグナル強度をルシフェラーゼ活性で評価
Therefore, the present inventors obtained (1) four commercially available Wnt / βeta-catenin pathway inhibitors (quercetin, ionomycin, imatinib, hexachlorophene), and (2) other five types We synthesize Wnt / βeta-catenin pathway inhibitory low molecular weight compounds NSC66808036, PKF-115-584, CPG049090, PNU-74654, ICG-001, and examine hepatocyte differentiation-inducing action. UE7T-13 cells) and human umbilical cord blood-derived cells (UCBTERT-21 cells), and as a result of examining the above-mentioned effects with respect to the following points, four types of these as demonstrated in the examples described later Inhibitors of Wnt / βeta-catenin pathway (quercetin, ionomycin, Hexa chloro Fen, PKF115-584) in which the mesenchymal stem cells were found to be induced to differentiate into stem cells.
1. 1. Liver-specific transcription factor expression 2. Liver-specific protein expression 3. Glycogen synthesis 4. Urea synthesis Signal strength of Wnt / βeta-catenin pathway by TCF activity is evaluated by luciferase activity
こうして見出された本実施形態に係る間葉系幹細胞の肝細胞への分化誘導剤は、Wnt/β−カテニン経路を抑制する有機低分子量化合物(ケルセチン、イオノマイシン、ヘキサクロロフェン、PKF115−584)を含み、これらの低分子化合物は蛋白製剤や核酸製剤に比べ、安定性、安全性などのフィージビリティにおいて優れ、再生医療の実現に有力な方法と期待される。これまでに上記の合成された5種類と既に市販されている3種類の合計8種類のWnt/βeta−catenin経路抑制性の低分子化合物のうち4種類(ケルセチン、イオノマイシン、ヘキサクロロフェン、PKF115−584)について、ヒト間葉系幹細胞から肝細胞への分化誘導能を、RNA干渉と比較検討しており、いずれも優れた分化誘導能を示している。また、当然のことながら、これらの有機低分子量化合物(ケルセチン、イオノマイシン、ヘキサクロロフェン、PKF115−584)RNA干渉の場合に比べて安定性、安全性などのフィージビリティにおいて著しく優れている。 Thus, the differentiation-inducing agent for mesenchymal stem cells according to the present embodiment thus found is a low-molecular weight organic compound (quercetin, ionomycin, hexachlorophene, PKF115-584) that suppresses the Wnt / β-catenin pathway. In addition, these low molecular weight compounds are superior in feasibility such as stability and safety as compared with protein preparations and nucleic acid preparations, and are expected to be effective methods for realizing regenerative medicine. Of the total of 8 types of Wnt / βeta-catenin pathway inhibitory low molecular weight compounds that have been synthesized so far and 3 types already commercially available, 4 types (quercetin, ionomycin, hexachlorophene, PKF115-584) ), The ability to induce differentiation from human mesenchymal stem cells to hepatocytes is compared with RNA interference, and both show excellent differentiation-inducing ability. Further, as a matter of course, these organic low molecular weight compounds (quercetin, ionomycin, hexachlorophene, PKF115-584) are remarkably excellent in feasibility such as stability and safety as compared with the case of RNA interference.
すなわち、本実施形態に係る間葉系幹細胞の肝細胞への分化誘導剤は、ヘキサクロロフェン、ケルセチン、イオノマイシン、PKF115−584からなる群から選ばれる1種以上の化合物またはその類縁体を含む、分化誘導剤である。ここで、本明細書において「類縁体」(analog)とは、いわゆる「誘導体」(derivative)を含む概念であり、類似体、類似化合物、類縁化合物などと表現されることもある。つまり、「類縁体」とは、ある化合物と受容体結合特性などの分子生物学的な性質や構造が類似しているが、ある化合物の原子または原子団が別の原子または原子団と置換された組成を持つ別の化合物のことを含む。医薬品化学においては、期待される生理活性を持つ化合物が見つかると、より高い活性を持つ化合物を求めてその化合物の誘導体の探索を行なうことがよくある。このとき、探索の出発点となった化合物をリード化合物、その誘導体をアナログと呼ぶ。もちろん、本明細書において「類縁体」とは、リード化合物に対するアナログを含む概念である。そのため、本明細書において「類縁体」とは、後述する薬理的に許容される誘導体および薬理的に許容される塩を含む。 That is, the agent for inducing differentiation of mesenchymal stem cells into hepatocytes according to this embodiment includes one or more compounds selected from the group consisting of hexachlorophene, quercetin, ionomycin, and PKF115-584, or analogs thereof. It is an inducer. Here, in this specification, “analog” is a concept including a so-called “derivative” and may be expressed as an analog, a similar compound, an analog, and the like. In other words, an “analog” is similar to a compound in terms of molecular biological properties and structures, such as receptor binding properties, but an atom or group of a compound is replaced with another atom or group of atoms. Another compound having a specific composition. In medicinal chemistry, when a compound having an expected physiological activity is found, a compound having a higher activity is often searched for a derivative of the compound. At this time, the compound that is the starting point of the search is called a lead compound, and its derivative is called an analog. Of course, in the present specification, the “analog” is a concept including an analog for a lead compound. Therefore, in the present specification, the “analog” includes pharmacologically acceptable derivatives and pharmacologically acceptable salts described later.
本明細書において「誘導体」(derivative)とは、ある有機化合物を母体として考えたとき、官能基の導入、酸化、還元、または原子の置き換えもしくは原子の付加などによって、母体の構造や性質を大幅に変えない程度の改変がなされた化合物のことを意味する。なおその改変は実際の化学反応として行えることもあるが、机上のものでも構わない。本明細書において「薬理的に許容される誘導体」は、所望の効果を有する化合物であれば限定されず、本発明に係る化合物の薬理的に許容される塩、溶媒和物、異性体、またはプロドラッグ等(例えばエステル)の形態を含む。またこの薬理的に許容される誘導体は、患者に投与すると、本発明に係る化合物またはその活性代謝物もしくはその残基を(直接的または間接的に)提供される任意の他の化合物を含む。そしてこのような薬理的に許容される誘導体は、当業者であれば過度の実験を行なうことなく得ることができる。例えば、[Burger’s Medicinal Chemistry And Drug Discovery, 5th Edition, Vol 1: Principles and Practice]を参照できる。なお好ましくは、本発明に係る化合物の薬理的に許容される塩または溶媒和物である。また所望の効果とは、本発明に係る化合物と実質的に同等の効果を含む。 In this specification, a “derivative” means that when an organic compound is considered as a base, the structure and properties of the base are greatly increased by introduction of a functional group, oxidation, reduction, substitution of atoms or addition of atoms. It means a compound that has been modified to the extent that it does not change. The modification may be performed as an actual chemical reaction, but it may be performed on a desk. In the present specification, the “pharmacologically acceptable derivative” is not limited as long as it has a desired effect, and is a pharmacologically acceptable salt, solvate, isomer, or compound of the present invention. Includes forms of prodrugs and the like (eg esters). This pharmacologically acceptable derivative also includes any other compound that, when administered to a patient, is provided (directly or indirectly) a compound according to the invention or an active metabolite thereof or residue thereof. Such pharmacologically acceptable derivatives can be obtained by those skilled in the art without undue experimentation. For example, [Burger's Medicinal Chemistry And Drug Discovery, 5th Edition, Vol 1: Principles and Practice] can be referred to. A pharmacologically acceptable salt or solvate of the compound according to the present invention is preferred. The desired effect includes an effect substantially equivalent to that of the compound according to the present invention.
本明細書において「薬理的に許容される塩」は、特に限定されないが、例えば任意の酸性(例えばカルボキシル)基で形成されるアニオン塩、または任意の塩基性(例えばアミノ)基で形成されるカチオン塩である。塩類には無機塩および有機塩を含み、[Berge,BighleyおよびMonkhouse、 J.Pharm.Sci., 1977, 66, 1−19]に記載されている塩が含まれる。 In the present specification, the “pharmacologically acceptable salt” is not particularly limited. For example, it is formed with an anion salt formed with any acidic (eg, carboxyl) group, or formed with any basic (eg, amino) group. Cationic salt. Salts include inorganic and organic salts [Berge, Bigley and Monkhouse, J. et al. Pharm. Sci. , 1977, 66, 1-19].
本明細書において「溶媒和物」は、溶質および溶媒によって形成される化合物である。溶媒和物については例えば、[J.Honig et al., The Van Nostrand Chemist’s Dictionary P650 (1953)]を参照できる。溶媒が水であれば形成される溶媒和物は水和物である。この溶媒は、溶質の生物活性を妨げないものが好ましい。そのような好ましい溶媒の例として、限定するものではないが、水、エタノール、および酢酸が挙げられる。最も好ましい溶媒は、水である。水和物は、大気に触れるかまたは再結晶するときに水分を吸収し、その結果、本発明化合物又はその塩は、場合によっては、吸湿水を有するか又は水和物となる。 As used herein, a “solvate” is a compound formed by a solute and a solvent. As for the solvate, for example, [J. Honig et al. , The Van Nostrand Chemist's Dictionary P650 (1953)]. If the solvent is water, the solvate formed is a hydrate. This solvent is preferably one that does not interfere with the biological activity of the solute. Examples of such preferred solvents include, without limitation, water, ethanol, and acetic acid. The most preferred solvent is water. Hydrates absorb moisture when exposed to the atmosphere or recrystallize, and as a result, the compounds of the present invention or their salts optionally have hygroscopic water or become hydrates.
本明細書において「異性体」は、分子式は同一だが構造が異なる分子を含む。鏡像異性体(エナンチオマー)、幾何(シス/トランス)異性体、または相互に鏡像ではない不斉中心を1個以上有する異性体(ジアステレオマー)を含む。 As used herein, “isomer” includes molecules having the same molecular formula but different structures. Includes enantiomers (enantiomers), geometric (cis / trans) isomers, or isomers having one or more asymmetric centers that are not mirror images of one another (diastereomers).
本明細書において「プロドラッグ」は、前駆体である化合物であって、その化合物を被験体へ投与した際に、代謝過程または種々化学反応によって化学的変化を起こし、本発明に係る化合物またはその塩もしくはその溶媒和物をもたらす化合物を含む。プロドラッグについては、例えば[T. Higuchi and V. Stella, “Pro−Drugs as Novel Delivery Systems”, A.C.S. Symposium Series, Volume 14]を参照できる。 As used herein, a “prodrug” is a compound that is a precursor, and undergoes a chemical change by metabolic processes or various chemical reactions when the compound is administered to a subject, and the compound according to the present invention or a compound thereof Including compounds that yield salts or solvates thereof. For prodrugs, for example, [T. Higuchi and V. Stella, “Pro-Drugs as Novel Delivery Systems”, A.A. C. S. See Symposium Series, Volume 14].
(i)ヘキサクロロフェン
本明細書において、「ヘキサクロロフェン」(hexachlorophene)とは、PubChemから引用すると、以下の特性を有する化合物であり、化学式(1)で表される。
Compound ID 3598
IUPAC: 3,4,6-trichloro-2-[(2,3,5-trichloro-6-hydroxyphenyl)methyl]phenol
Molecular Weight 406.90354[g/mol]
Molecular Formula C13H6Cl6O2
XLogP3 7.5
H-Bond Donor 2
H-Bond Acceptor 2
(I) Hexachlorophen In the present specification, “hexachlorophene” is a compound having the following characteristics and is represented by the chemical formula (1) when quoted from PubChem.
Compound ID 3598
IUPAC: 3,4,6-trichloro-2-[(2,3,5-trichloro-6-hydroxyphenyl) methyl] phenol
Molecular Weight 406.90354 [g / mol]
Molecular Formula C13H6Cl6O2
XLogP3 7.5
H-Bond Donor 2
H-Bond Acceptor 2
ヘキサクロロフェンの類縁体としては、特に限定するものではないが、例えばPubChemのCompound Structure Search において類似度(tanimoto係数)95%以上で検索すると、以下の9種類の化合物が類縁体に含まれる。なお、類縁体に含めるtanimoto係数の下限値は、特に限定されず、例えば、90%以上でもよく、91%以上でもよく、92%以上でもよく、93%以上でもよく、94%以上でもよく、95%以上でもよく、96%以上でもよく、97%以上でもよく、98%以上でもよく、99%以上でもよい。類似度(tanimoto係数)が大きければ大きいほどリード化合物に構造・生理活性などが近似した類縁体である可能性が高くなる。なお、tanimoto係数の計算式は以下のとおりであり、ケモインフォマティクスの分野では最も頻繁に使われる権威ある化合物同士の類似係数である。 The analog of hexachlorophene is not particularly limited. For example, when searching with Compound Structure Search of PubChem with a similarity (tanimoto coefficient) of 95% or more, the following nine types of compounds are included in the analog. The lower limit of the tanimoto coefficient included in the analog is not particularly limited, and may be, for example, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, It may be 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more. The greater the degree of similarity (tanimoto coefficient), the higher the possibility of being an analog having a structure / physiological activity that approximates the lead compound. The formula for calculating the tanimoto coefficient is as follows, and is a similarity coefficient between the authoritative compounds most frequently used in the field of chemoinformatics.
Tanimoto = AB / ( A + B - AB )
Where:
Tanimoto is the Tanimoto score, a fraction between 0 and 1.
AB is the count of bits set after bit-wise & of fingerprints A and B
A is the count of bits set in fingerprint A
B is the count of bits set in fingerprint B
Tanimoto = AB / (A + B-AB)
Where:
Tanimoto is the Tanimoto score, a fraction between 0 and 1.
AB is the count of bits set after bit-wise & of fingerprints A and B
A is the count of bits set in fingerprint A
B is the count of bits set in fingerprint B
ヘキサクロロフェンの類似度(tanimoto係数)95%以上の類縁体一覧
1: CID: 3598
hexachlorophene; pHisoHex; Gamophen
IUPAC: 3,4,6-trichloro-2-[(2,3,5-trichloro-6-hydroxyphenyl)methyl]phenol
MW: 406.903540 g/mol | MF: C13H6Cl6O2
Tested in BioAssays: All: 505, Active: 114
Anti-Infective Agents, Local more
2: CID: 20372044
IUPAC: 3,4,6-trichloro-2-[(3,5-dichloro-2-hydroxyphenyl)methyl]phenol
MW: 372.458480 g/mol | MF: C13H7Cl5O2
3: CID: 23669625
Isobac; Isobac 20; Caswell No. 566A
IUPAC: sodium 3,4,6-trichloro-2-[(2,3,5-trichloro-6-hydroxyphenyl)methyl]phenolate
MW: 428.885370 g/mol | MF: C13H5Cl6NaO2
4: CID: 22088194
MW: 406.903540 g/mol | MF: C13H6Cl6O2-2
5: CID: 74742
CID74742; 3,4,4’,5’,6,6’-Hexachloro-2,2’-methylenediphenol; Phenol, 3,4,4’,5’,6,6’-hexachloro-2,2’-methylenedi-
IUPAC: 2,3,4-trichloro-6-[(2,3,5-trichloro-6-hydroxyphenyl)methyl]phenol
MW: 406.903540 g/mol | MF: C13H6Cl6O2
6: CID: 22954419
MW: 406.903540 g/mol | MF: C13H6Cl6O2
7: CID: 209168
Phenol, 2,2’-methylenebis(3,5,6-trichloro-; 2,2’-Methylenebis(3,5,6-trichlorophenol); CID209168
IUPAC: 2,3,5-trichloro-6-[(3,4,6-trichloro-2-hydroxyphenyl)methyl]phenol
MW: 406.903540 g/mol | MF: C13H6Cl6O2
8: CID: 23349392
IUPAC: 3,4,6-trichloro-2-[(2-hydroxyphenyl)methyl]phenol
MW: 303.568360 g/mol | MF: C13H9Cl3O2
9: CID: 5282359
CID5282359; C14203; 2,2’,3,3’,5,5’-Hexachloro-6-biphenylol
IUPAC: 3,4,6-trichloro-2-(2,3,5-trichlorophenyl)phenol
MW: 376.877560 g/mol | MF: C12H4Cl6O
List of analogs with hexachlorophene similarity (tanimoto coefficient) of 95% or more
1: CID: 3598
hexachlorophene; pHisoHex; Gamophen
IUPAC: 3,4,6-trichloro-2-[(2,3,5-trichloro-6-hydroxyphenyl) methyl] phenol
MW: 406.903540 g / mol | MF: C13H6Cl6O2
Tested in BioAssays: All: 505, Active: 114
Anti-Infective Agents, Local more
2: CID: 20372044
IUPAC: 3,4,6-trichloro-2-[(3,5-dichloro-2-hydroxyphenyl) methyl] phenol
MW: 372.458480 g / mol | MF: C13H7Cl5O2
3: CID: 23669625
Isobac; Isobac 20; Caswell No. 566A
IUPAC: sodium 3,4,6-trichloro-2-[(2,3,5-trichloro-6-hydroxyphenyl) methyl] phenolate
MW: 428.885370 g / mol | MF: C13H5Cl6NaO2
4: CID: 22088194
MW: 406.903540 g / mol | MF: C13H6Cl6O2-2
5: CID: 74742
CID74742; 3,4,4 ', 5', 6,6'-Hexachloro-2,2'-methylenediphenol; Phenol, 3,4,4 ', 5', 6,6'-hexachloro-2,2'- methylenedi-
IUPAC: 2,3,4-trichloro-6-[(2,3,5-trichloro-6-hydroxyphenyl) methyl] phenol
MW: 406.903540 g / mol | MF: C13H6Cl6O2
6: CID: 22954419
MW: 406.903540 g / mol | MF: C13H6Cl6O2
7: CID: 209168
Phenol, 2,2'-methylenebis (3,5,6-trichloro-; 2,2'-Methylenebis (3,5,6-trichlorophenol); CID209168
IUPAC: 2,3,5-trichloro-6-[(3,4,6-trichloro-2-hydroxyphenyl) methyl] phenol
MW: 406.903540 g / mol | MF: C13H6Cl6O2
8: CID: 23349392
IUPAC: 3,4,6-trichloro-2-[(2-hydroxyphenyl) methyl] phenol
MW: 303.568360 g / mol | MF: C13H9Cl3O2
9: CID: 5282359
CID5282359; C14203; 2,2 ', 3,3', 5,5'-Hexachloro-6-biphenylol
IUPAC: 3,4,6-trichloro-2- (2,3,5-trichlorophenyl) phenol
MW: 376.877560 g / mol | MF: C12H4Cl6O
当業者であれば、後述の実施例の実験データを参照すれば、これらの類似度(tanimoto係数)95%以上の9種類の化合物が、当然に間葉系幹細胞の肝細胞への分化を誘導する性質を有することを理解できる。 If a person skilled in the art refers to the experimental data of the examples described later, these nine compounds having a similarity (tanimoto coefficient) of 95% or more naturally induce differentiation of mesenchymal stem cells into hepatocytes. Can be understood.
(ii)ケルセチン
本明細書において、「ケルセチン」(Quercetin)とは、PubChemから引用すると、以下の特性を有する化合物であり、化学式(2)で表される。
Compound ID 5280343
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one
Molecular Weight 302.2357 [g/mol]
Molecular Formula C15H10O7
XLogP3 1.5
H-Bond Donor 5
H-Bond Acceptor 7
(Ii) Quercetin In this specification, “Quercetin” is a compound having the following characteristics and is represented by the chemical formula (2), when quoted from PubChem.
Compound ID 5280343
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one
Molecular Weight 302.2357 [g / mol]
Molecular Formula C15H10O7
XLogP3 1.5
H-Bond Donor 5
H-Bond Acceptor 7
ケルセチンの類縁体としては、特に限定するものではないが、例えばPubChemのCompound Structure Search において類似度(tanimoto係数)95%以上で検索すると、以下の233種類の化合物が類縁体に含まれる。なお、類縁体に含めるtanimoto係数の下限値は、特に限定されず、例えば、90%以上でもよく、91%以上でもよく、92%以上でもよく、93%以上でもよく、94%以上でもよく、95%以上でもよく、96%以上でもよく、97%以上でもよく、98%以上でもよく、99%以上でもよい。類似度(tanimoto係数)が大きければ大きいほどリード化合物に構造・生理活性などが近似した類縁体である可能性が高くなる。なお、tanimoto係数の計算式は既述のとおりであり、ケモインフォマティクスの分野では最も頻繁に使われる権威ある化合物同士の類似係数である。 The analog of quercetin is not particularly limited. For example, when a search is made with a compound structure search of PubChem with a similarity (tanimoto coefficient) of 95% or more, the following 233 types of compounds are included in the analog. The lower limit value of the tanimoto coefficient included in the analog is not particularly limited, and may be, for example, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, It may be 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more. The greater the degree of similarity (tanimoto coefficient), the higher the possibility of being an analog having a structure / physiological activity that approximates the lead compound. The formula for calculating the tanimoto coefficient is as described above, and is the similarity coefficient between the authoritative compounds most frequently used in the field of chemoinformatics.
ケルセチンの類似度(tanimoto係数)95%以上の類縁体一覧
1: CID: 5280343
quercetin; Sophoretin; Meletin
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
Tested in BioAssays: All: 281, Active: 55
Antioxidants more
2: CID: 20670067
IUPAC: actinium; 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one
MW: 1437.374435 g/mol | MF: C15H10Ac5O7
3: CID: 5281614
Fisetin; Cotinin; Superfustel
IUPAC: 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
Tested in BioAssays: All: 174, Active: 28
4: CID: 5281692
Robinetin; Norkanugin; 5-Deoxymyricetin
IUPAC: 3,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
Tested in BioAssays: All: 24, Active: 2
5: CID: 5284452
Quercetin dihydrate; quercetin; Quercetine dihydrate
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one dihydrate
MW: 338.266260 g/mol | MF: C15H14O9
Tested in BioAssays: All: 98, Active: 12
Antioxidants more
6: CID: 10818722
CID10818722; [2,3-dihydroxy-6-(3,5,7-trihydroxy-4-oxo-chromen-2-yl)phenyl]thallium
IUPAC: [2,3-dihydroxy-6-(3,5,7-trihydroxy-4-oxochromen-2-yl)phenyl]thallium
MW: 505.611060 g/mol | MF: C15H9O7Tl
7: CID: 16212154
Quercetin hydrate; MLS001074343; MLS002153851
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one hydrate
MW: 320.250980 g/mol | MF: C15H12O8
Tested in BioAssays: All: 132, Active: 14
8: CID: 16213065
Fisetin; 5-Deoxyquercetin; Natural Brown- 1
IUPAC: 2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one hydrate
MW: 304.251580 g/mol | MF: C15H12O7
9: CID: 24187083
NSC58588; 7255-55-2
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one; zirconium
MW: 393.459700 g/mol | MF: C15H10O7Zr
Tested in BioAssays: All: 1, Active: 0
10: CID: 25031947
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one; selenium
MW: 381.195700 g/mol | MF: C15H10O7Se
11: CID: 12305312
IUPAC: 6,8-dideuterio-3,5,7-trihydroxy-2-(2,3,6-trideuterio-4,5-dihydroxyphenyl)chromen-4-one
MW: 307.266509 g/mol | MF: C15H10O7
12: CID: 21600688
IUPAC: 3,5,7-trihydroxy-2-(2,3,6-trideuterio-4,5-dihydroxyphenyl)chromen-4-one
MW: 305.254185 g/mol | MF: C15H10O7
13: CID: 23105025
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5-dihydroperoxy-7-hydroxychromen-4-one
MW: 334.234500 g/mol | MF: C15H10O9
14: CID: 5281672
myricetin; Cannabiscetin; Myricetol
IUPAC: 3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 318.235100 g/mol | MF: C15H10O8
Tested in BioAssays: All: 277, Active: 48
15: CID: 12309893
IUPAC: 8-deuterio-3,7-dihydroxy-2-(2,3,6-trideuterio-4,5-dihydroxyphenyl)chromen-4-one
MW: 290.260947 g/mol | MF: C15H10O6
16: CID: 25201643
myricetin
IUPAC: 2,6-dihydroxy-4-(3,5,7-trihydroxy-4-oxochromen-2-yl)phenolate
MW: 317.227160 g/mol | MF: C15H9O8-
17: CID: 5280445
luteolin; Luteoline; Luteolol
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
Tested in BioAssays: All: 258, Active: 41
18: CID: 5321864
5,7,2’,3’-Tetrahydroxyflavone; LMPK12110137; CID5321864
IUPAC: 2-(2,3-dihydroxyphenyl)-5,7-dihydroxychromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
19: CID: 18471844
ZINC14644152
IUPAC: 5,7-dihydroxy-2-(2,3,4-trihydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
20: CID: 22339062
IUPAC: 3,5-dihydroxy-2-(2,3,4-trihydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
21: CID: 25201972
luteolin; 5734-TETRAHYDROXYFLAVONE; 3’,4’,5,7-Tetrahydroxyflavone
IUPAC: 4-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxyphenolate
MW: 285.228360 g/mol | MF: C15H9O6-
22: CID: 26034
5,7-Di-O-methylquercetin; BRN 0344074; CID26034
IUPAC: 2-(3,4-dihydroxyphenyl)-3-hydroxy-5,7-dimethoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
23: CID: 5281604
Azaleatin; 5-O-Methylquercetin; Quercetin 5-methyl ether
IUPAC: 2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-5-methoxychromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
24: CID: 5281638
6-Hydroxykaempferol; CHEBI:563476; LMPK12112860
IUPAC: 3,5,6,7-tetrahydroxy-2-(4-hydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
25: CID: 5281691
Rhamnetin; 7-Methoxyquercetin; 7-Methylquercetin
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methoxychromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
Tested in BioAssays: All: 117, Active: 6
26: CID: 10598612
CID10598612; 2-(3,4-dihydroxy-2-iodo-phenyl)-3,5,7-trihydroxy-chromen-4-one
IUPAC: 2-(3,4-dihydroxy-2-iodophenyl)-3,5,7-trihydroxychromen-4-one
MW: 428.132230 g/mol | MF: C15H9IO7
27: CID: 15233950
LMPK12112802
IUPAC: 3,5,6,7-tetrahydroxy-2-phenylchromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
28: CID: 17840574
IUPAC: (3,5,6,7-tetrahydroxy-2-phenylchromen-4-ylidene)oxidanium
MW: 287.244240 g/mol | MF: C15H11O6+
29: CID: 24721675
IUPAC: 3,7-dihydroxy-2-(2,4,5-trihydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
30: CID: 25205335
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one; platinum(4+); dichloride
MW: 568.219700 g/mol | MF: C15H10Cl2O7Pt+2
31: CID: 25206803
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one; platinum(4+); chloride; hydrochloride
MW: 569.227640 g/mol | MF: C15H11Cl2O7Pt+3
32: CID: 5322065
7,3’,4’-Trihydroxyflavone; 3’,4’,7-Trihydroxyflavone; BRN 0253031
IUPAC: 2-(3,4-dihydroxyphenyl)-7-hydroxychromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
33: CID: 5393164
7,3,4,5-tetrahydroxyflavone; CHEBI:519698; LMPK12110051
IUPAC: 7-hydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
34: CID: 10517292
CID10517292; 3-hydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
IUPAC: 3-hydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
35: CID: 16662883
IUPAC: 2-(2,3-dihydroxyphenyl)-7-hydroxychromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
36: CID: 21158518
IUPAC: 7-hydroxy-2-(2,3,4-trihydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
37: CID: 5281701
Tricetin; Spectrum_001591; SpecPlus_000826
IUPAC: 5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
Tested in BioAssays: All: 63, Active: 9
38: CID: 12359024
IUPAC: 3,6,8-trideuterio-5,7-dihydroxy-2-(2,3,6-trideuterio-4,5-dihydroxyphenyl)chromen-4-one
MW: 292.273271 g/mol | MF: C15H10O6
39: CID: 12359025
IUPAC: 3-deuterio-5,7-dihydroxy-2-(2,3,6-trideuterio-4,5-dihydroxyphenyl)chromen-4-one
MW: 290.260947 g/mol | MF: C15H10O6
40: CID: 627207
CHEBI:347700; CID627207; 3-Hydroxy-2-(3,4-dihydroxyphenyl)-7-methoxy-4H-chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-3-hydroxy-7-methoxychromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
41: CID: 5280417
3,7-Di-O-methylquercetin; CHEBI:18010; MolPort-001-742-139
IUPAC: 2-(3,4-dihydroxyphenyl)-5-hydroxy-3,7-dimethoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
42: CID: 5280681
3-O-Methylquercetin; 3-Methoxy quercetin; Quercetin-3-methylether
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-methoxychromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
Tested in BioAssays: All: 234, Active: 11
43: CID: 5281680
Quercetagetin; 6-Hydroxyquercetin; CHEBI:202888
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,6,7-tetrahydroxychromen-4-one
MW: 318.235100 g/mol | MF: C15H10O8
44: CID: 5319492
Flavone der.; AIDS071769; CHEBI:219000
IUPAC: 2-(3,4-dihydroxyphenyl)-3,6,7-trihydroxychromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
45: CID: 5489501
3,5-Di-O-methylquercetin; LMPK12112730; CID5489501
IUPAC: 2-(3,4-dihydroxyphenyl)-7-hydroxy-3,5-dimethoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
46: CID: 10516160
CID10516160; 3,7,8-trihydroxy-2-phenyl-chromen-4-one
IUPAC: 3,7,8-trihydroxy-2-phenylchromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
47: CID: 15560442
LMPK12111605
IUPAC: 2-(3,4-dihydroxyphenyl)-3,7,8-trihydroxychromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
48: CID: 21676161
IUPAC: [2-hydroxy-5-(3,5,7-trihydroxy-4-oxochromen-2-yl)phenyl] sulfate
MW: 381.290960 g/mol | MF: C15H9O10S-
49: CID: 21676163
IUPAC: [2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-4-oxochromen-7-yl] sulfate
MW: 381.290960 g/mol | MF: C15H9O10S-
50: CID: 21676164
IUPAC: [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl] sulfate
MW: 381.290960 g/mol | MF: C15H9O10S-
51: CID: 22239065
LMPK12111601; ZINC12359395
IUPAC: 3,7,8-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
52: CID: 24721178
IUPAC: 3,7,8-trihydroxy-2-(2-hydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
53: CID: 25202270
3-methoxyluteolin; 3-O-Methylquercetin; 3’,4’,5,7-Tetrahydroxy-3-methoxyflavone
IUPAC: 4-(5,7-dihydroxy-3-methoxy-4-oxochromen-2-yl)-2-hydroxyphenolate
MW: 315.254340 g/mol | MF: C16H11O7-
54: CID: 25203115
Quercetin 3-sulfate; CPD-1822
IUPAC: [5,7-dihydroxy-2-(3-hydroxy-4-oxidophenyl)-4-oxochromen-3-yl] sulfate
MW: 380.283020 g/mol | MF: C15H8O10S-2
55: CID: 25206804
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one; platinum(4+); tetrachloride
MW: 639.125700 g/mol | MF: C15H10Cl4O7Pt
56: CID: 16113029
LMPK12112522
IUPAC: 3,5,7-trihydroxy-2-(2,4,5-trihydroxyphenyl)chromen-4-one
MW: 318.235100 g/mol | MF: C15H10O8
57: CID: 15661823
ZINC04349582
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-methylchromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
58: CID: 6477685
AIDS154808; CHEBI:480357; AIDS-154808
IUPAC: 2-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5,7-dihydroxychromen-4-one
MW: 312.273580 g/mol | MF: C17H12O6
59: CID: 88281
5,3’,4’-Trihydroxyflavone; TNP00056; CHEBI:490257
IUPAC: 2-(3,4-dihydroxyphenyl)-5-hydroxychromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
Tested in BioAssays: All: 81, Active: 10
60: CID: 17851159
IUPAC: 5-hydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
61: CID: 147651
Quercetin trimethyl ether; ZINC00338058; CID147651
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trimethoxychromen-4-one
MW: 344.315440 g/mol | MF: C18H16O7
62: CID: 5280362
Quercetin 3-sulfate; quercetin 3-(hydrogen sulfate); CHEBI:17730
IUPAC: [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl] hydrogen sulfate
MW: 382.298900 g/mol | MF: C15H10O10S
63: CID: 5280544
Herbacetin; 8-Hydroxykaempferol; LMPK12113149
IUPAC: 3,5,7,8-tetrahydroxy-2-(4-hydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
64: CID: 5281654
Isorhamnetin; 3-Methylquercetin; Isorhamnetol
IUPAC: 3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
Tested in BioAssays: All: 18, Active: 2
65: CID: 5281679
Pinoquercetin; 6-C-Methylquercetin; LMPK12112292
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-6-methylchromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
66: CID: 5281699
Tamarixetin; 4’-O-Methylquercetin; Quercetin 4’-methyl ether
IUPAC: 3,5,7-trihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
67: CID: 5320287
Ombuin; 4’,7-Dimethylquercetin; 7,4’-Di-O-methylquercetin
IUPAC: 3,5-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-methoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
68: CID: 5320945
Rhamnazin; 3’,7-Dimethylquercetin; 7,3’-Di-O-methylquercetin
IUPAC: 3,5-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-7-methoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
Tested in BioAssays: All: 61, Active: 1
69: CID: 5362017
8-Hydroxygalangin; 3,5,7,8-Tetrahydroxyflavone; BRN 0295943
IUPAC: 3,5,7,8-tetrahydroxy-2-phenylchromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
70: CID: 5388949
nchembio718-comp16; ZINC04731234; CID5388949
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-8-methylchromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
71: CID: 9839293
CHEBI:304347; LMPK12111567; CID9839293
IUPAC: 2-(3,4-dihydroxyphenyl)-7-hydroxy-3-methoxychromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
72: CID: 10022760
LMPK12112305; CID10022760; 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-4-oxo-7-sulfooxy-chromene
IUPAC: [2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-4-oxochromen-7-yl] hydrogen sulfate
MW: 382.298900 g/mol | MF: C15H10O10S
73: CID: 11012936
CID11012936; 3,5-dihydroxy-2-(3-hydroxy-2-methoxy-phenyl)-7-methoxy-chromen-4-one
IUPAC: 3,5-dihydroxy-2-(3-hydroxy-2-methoxyphenyl)-7-methoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
74: CID: 14162696
LMPK12112547
IUPAC: 3,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-methoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
75: CID: 15227607
LMPK12112548
IUPAC: 3,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-5-methoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
76: CID: 20504452
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one; methoxymethane
MW: 348.304140 g/mol | MF: C17H16O8
77: CID: 21676162
LMPK12112306
IUPAC: [2-hydroxy-5-(3,5,7-trihydroxy-4-oxochromen-2-yl)phenyl] hydrogen sulfate
MW: 382.298900 g/mol | MF: C15H10O10S
78: CID: 21676167
IUPAC: [5,7-dihydroxy-2-(4-hydroxy-3-sulfonatooxyphenyl)-4-oxochromen-3-yl] sulfate
MW: 460.346220 g/mol | MF: C15H8O13S2-2
79: CID: 21676170
IUPAC: [5,7-dihydroxy-2-(3-hydroxy-4-sulfonatooxyphenyl)-4-oxochromen-3-yl] sulfate
MW: 460.346220 g/mol | MF: C15H8O13S2-2
80: CID: 21676173
IUPAC: [3,5-dihydroxy-2-(3-hydroxy-4-sulfonatooxyphenyl)-4-oxochromen-7-yl] sulfate
MW: 460.346220 g/mol | MF: C15H8O13S2-2
81: CID: 23670118
CHEBI:604112; potassium 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-4H-chromen-3-yl sulfate
IUPAC: potassium [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl] sulfate
MW: 420.389260 g/mol | MF: C15H9KO10S
82: CID: 25164913
IUPAC: [2-hydroxy-4-(3,5,7-trihydroxy-4-oxochromen-2-yl)phenyl] hydrogen sulfate
MW: 382.298900 g/mol | MF: C15H10O10S
83: CID: 25202413
Isorhamnetin; 3-Methylquercetin; 3’-Methoxyquercetin
IUPAC: 5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-4-oxochromen-3-olate
MW: 315.254340 g/mol | MF: C16H11O7-
84: CID: 25206967
IUPAC: azane; 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one; platinum(2+); dichloride
MW: 585.250220 g/mol | MF: C15H13Cl2NO7Pt
85: CID: 44472542
IUPAC: azane; 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one; platinum
MW: 531.374740 g/mol | MF: C15H16N2O7Pt
86: CID: 5319731
5-Methylmyricetin; LMPK12112555; CID5319731
IUPAC: 3,7-dihydroxy-5-methoxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 332.261680 g/mol | MF: C16H12O8
87: CID: 14376433
LMPK12113049
IUPAC: 3,5,6,7-tetrahydroxy-2-(2,3,4-trihydroxyphenyl)chromen-4-one
MW: 334.234500 g/mol | MF: C15H10O9
88: CID: 44259636
LMPK12112664
IUPAC: 3,5-dihydroxy-7-methoxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 332.261680 g/mol | MF: C16H12O8
89: CID: 5280616
2’-hydroxypseudobaptigenin; CID5280616; C03662
IUPAC: 7-hydroxy-2-(2,3,4,5-tetrahydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
90: CID: 5281605
baicalein; 5,6,7-Trihydroxyflavone; Biacalein
IUPAC: 5,6,7-trihydroxy-2-phenylchromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
Tested in BioAssays: All: 120, Active: 30
Prostaglandin Antagonists more
91: CID: 5281642
6-Hydroxyluteolin; Demethylpedalitin; 6-OH-Luteolin
IUPAC: 2-(3,4-dihydroxyphenyl)-5,6,7-trihydroxychromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
92: CID: 5281697
Scutellarein; Isocarthamidin; Flavonoid
IUPAC: 5,6,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
93: CID: 5318214
Hydroxygenkwanin; 7-O-Methylluteolin; MEGxp0_000798
IUPAC: 2-(3,4-dihydroxyphenyl)-5-hydroxy-7-methoxychromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
94: CID: 5702782
baicalein; 5,6,7-Trihydroxyflavone; OR1525T
IUPAC: 5,6,7-trihydroxy-2-phenylchromen-4-one hydrate
MW: 288.252180 g/mol | MF: C15H12O6
Prostaglandin Antagonists more
95: CID: 13964548
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dimethoxychromen-4-one
MW: 314.289460 g/mol | MF: C17H14O6
96: CID: 13964550
LMPK12110965
IUPAC: 2-(3,4-dihydroxyphenyl)-7-hydroxy-5-methoxychromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
97: CID: 18372862
IUPAC: 2-(3,4-dihydroxyphenyl)-3-hydroxy-5-methoxychromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
98: CID: 5281649
Isoetin; LMPK12110940; 5,7,2’,4’,5’-Pentahydroxyflavone
IUPAC: 5,7-dihydroxy-2-(2,4,5-trihydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
99: CID: 6477684
AIDS154807; CHEBI:480359; AIDS-154807
IUPAC: 2-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-7-hydroxychromen-4-one
MW: 296.274180 g/mol | MF: C17H12O5
100: CID: 10636768
CHEBI:185726; CID10636768; 2-(3,4-Dihydroxy-benzyl)-7-hydroxy-chromen-4-one
IUPAC: 2-[(3,4-dihydroxyphenyl)methyl]-7-hydroxychromen-4-one
MW: 284.263480 g/mol | MF: C16H12O5
101: CID: 12417670
IUPAC: 2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
102: CID: 22507438
IUPAC: 2-(2,3,4-trihydroxyphenyl)chromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
103: CID: 628780
CID628780; 3-Hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-methoxy-4H-chromen-4-one
IUPAC: 3-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-methoxychromen-4-one
MW: 314.289460 g/mol | MF: C17H14O6
104: CID: 4125009
CID4125009; 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-6,8-bis(3-methylbut-2-enyl)chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-6,8-bis(3-methylbut-2-enyl)chromen-4-one
MW: 438.469740 g/mol | MF: C25H26O7
105: CID: 5280402
Quercetin 3,3’-bissulfate; CHEBI:17875; LMPK12112308
IUPAC: [5,7-dihydroxy-2-(4-hydroxy-3-sulfooxyphenyl)-4-oxochromen-3-yl] hydrogen sulfate
MW: 462.362100 g/mol | MF: C15H10O13S2
106: CID: 5280403
Quercetin 3,4’-bissulfate; CHEBI:18030; LMPK12112309
IUPAC: [5,7-dihydroxy-2-(3-hydroxy-4-sulfooxyphenyl)-4-oxochromen-3-yl] hydrogen sulfate
MW: 462.362100 g/mol | MF: C15H10O13S2
107: CID: 5280647
Gossypetin; Articulatidin; Equisporol
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7,8-tetrahydroxychromen-4-one
MW: 318.235100 g/mol | MF: C15H10O8
Tested in BioAssays: All: 54, Active: 8
108: CID: 5316900
Quercetin der.; 3,3’-Dimethylquercetin; 3,3’-Dimethoxyquercetin
IUPAC: 5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-methoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
109: CID: 5378244
LMPK12111569; CID5378244; 3,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-chromen-4-one
IUPAC: 3,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
110: CID: 5380905
ACon1_001466; CHEBI:221146; MolPort-001-741-117
IUPAC: 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3-methoxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
Tested in BioAssays: All: 1, Active: 0
111: CID: 5481966
Gancaonin P; AIDS095976; CHEBI:565528
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-6-(3-methylbut-2-enyl)chromen-4-one
MW: 370.352720 g/mol | MF: C20H18O7
112: CID: 5482101
Geraldol; SPECTRUM1505149; BIDF1020
IUPAC: 3,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
Tested in BioAssays: All: 52, Active: 3
113: CID: 6452329
M7HEQ; 7-O-beta-Hydroxyethylquercetin; 7-O-(beta-Hydroxyethyl)quercetin
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-(2-hydroxyethoxy)chromen-4-one
MW: 346.288260 g/mol | MF: C17H14O8
114: CID: 9799499
CHEBI:420898; ZINC03918592; CID9799499
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-8-(3-methylbut-2-enyl)chromen-4-one
MW: 370.352720 g/mol | MF: C20H18O7
115: CID: 9949390
CHEBI:303634; CID9949390; 2-(3,4-Dihydroxy-phenyl)-3-hydroxy-7-(2-hydroxy-ethoxy)-chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-3-hydroxy-7-(2-hydroxyethoxy)chromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
116: CID: 10004518
CID10004518; 3,5-dihydroxy-2-(3-hydroxy-4-sulfooxy-phenyl)-4-oxo-7-sulfooxy-chromene
IUPAC: [3,5-dihydroxy-2-(3-hydroxy-4-sulfooxyphenyl)-4-oxochromen-7-yl] hydrogen sulfate
MW: 462.362100 g/mol | MF: C15H10O13S2
117: CID: 10050405
CID10050405; 2-(3,4-dihydroxyphenyl)-7-dodecoxy-3,5-dihydroxy-chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-7-dodecoxy-3,5-dihydroxychromen-4-one
MW: 470.554660 g/mol | MF: C27H34O7
118: CID: 10895435
CHEBI:565814; CID10895435; 5,7,3’,4’-tetrahydroxy-6-geranylflavono
IUPAC: 2-(3,4-dihydroxyphenyl)-6-[(2E)-3,7-dimethylocta-2,6-dienyl]-3,5,7-trihydroxychromen-4-one
MW: 438.469740 g/mol | MF: C25H26O7
119: CID: 12988287
LMPK12112307
IUPAC: [2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxo-3-sulfooxychromen-7-yl] hydrogen sulfate
MW: 462.362100 g/mol | MF: C15H10O13S2
120: CID: 15895793
LMPK12111579
IUPAC: 3,7-dihydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)chromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
121: CID: 17918606
IUPAC: 3,5,6,7,8-pentahydroxy-2-(2-hydroxyphenyl)chromen-4-one
MW: 318.235100 g/mol | MF: C15H10O8
122: CID: 21633676
LMPK12112866
IUPAC: 3,5,6,7-tetrahydroxy-2-(4-methoxyphenyl)chromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
123: CID: 23320229
IUPAC: 2-(3,4-dihydroxyphenyl)-3-ethoxy-7-hydroxychromen-4-one
MW: 314.289460 g/mol | MF: C17H14O6
124: CID: 24206515
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-methoxychromen-4-one trihydrate
MW: 370.308120 g/mol | MF: C16H18O10
125: CID: 25201917
334578-HEXAHYDROXYFLAVONE; 3,3’,4’,5,7,8-Hexahydroxyflavone; 2-(3,4-dihydroxyphenyl)-3,5,7,8-tetrahydroxy-chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4-oxochromen-8-olate
MW: 317.227160 g/mol | MF: C15H9O8-
126: CID: 44259330
LMPK12112314
IUPAC: [4-(3,5-dihydroxy-7-hydroxysulfonothioyloxy-4-oxochromen-2-yl)-2-hydroxyphenyl] hydrogen sulfate
MW: 478.427700 g/mol | MF: C15H10O12S3
127: CID: 44259518
LMPK12112520
IUPAC: 3,5,7-trihydroxy-2-(3-hydroxy-2,4-dimethoxyphenyl)chromen-4-one
MW: 346.288260 g/mol | MF: C17H14O8
128: CID: 44260065
LMPK12113327
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5,6,7,8-pentahydroxychromen-4-one
MW: 334.234500 g/mol | MF: C15H10O9
129: CID: 24721651
IUPAC: 5-hydroxy-3,7-dimethoxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 346.288260 g/mol | MF: C17H14O8
130: CID: 25087106
Peflavit; Pentahydroxyflavone; 54077-18-8
IUPAC: 3,5,6,7,8-pentahydroxy-2-phenylchromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
131: CID: 25202871
quercetin-3,4-bissulfate; quercetin-3,4’-bissulfate; QUERCETIN-34-BISSULFATE
IUPAC: [2-hydroxy-4-(7-hydroxy-5-oxido-4-oxo-3-sulfonatooxychromen-2-yl)phenyl] sulfate
MW: 459.338280 g/mol | MF: C15H7O13S2-3
132: CID: 44259709
LMPK12112779
IUPAC: 5,7-dihydroxy-3-methoxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 332.261680 g/mol | MF: C16H12O8
133: CID: 676310
TNP00054; CHEBI:473681; CID676310
IUPAC: 7,8-dihydroxy-2-(3-hydroxyphenyl)chromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
Tested in BioAssays: All: 81, Active: 10
134: CID: 688798
7,8,3’,4’-tetrahydroxyflavone; 3’,4’,7,8-Tetrahydroxyflavone; CHEBI:473674
IUPAC: 2-(3,4-dihydroxyphenyl)-7,8-dihydroxychromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
135: CID: 5353357
6,7-dihydroxyflavone; 6,7-dihydroxy flavone; DivK1c_000421
IUPAC: 6,7-dihydroxy-2-phenylchromen-4-one
MW: 254.237500 g/mol | MF: C15H10O4
Tested in BioAssays: All: 86, Active: 5
136: CID: 5393155
ZINC00057757; CID5393155
IUPAC: 6,7-dihydroxy-2-(3-hydroxyphenyl)chromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
137: CID: 10355753
CHEBI:576113; CID10355753; 6,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
IUPAC: 6,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
138: CID: 10493280
CHEBI:303856; CID10493280; 2-(3,4-dihydroxyphenyl)-7-methoxy-chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-7-methoxychromen-4-one
MW: 284.263480 g/mol | MF: C16H12O5
139: CID: 10532672
CID10532672; 2-(3,4-dihydroxy-2-iodo-phenyl)-3,5,7-trihydroxy-6,8-diiodo-chromen-4-one
IUPAC: 2-(3,4-dihydroxy-2-iodanylphenyl)-3,5,7-trihydroxy-6,8-bis(iodanyl)chromen-4-one
MW: 691.930253 g/mol | MF: C15H7I3O7
140: CID: 10556475
CID10556475; 2-(3,4-dihydroxy-2-iodo-phenyl)-3,5,7-trihydroxy-6,8-diiodo-chromen-4-one
IUPAC: 2-(3,4-dihydroxy-2-iodophenyl)-3,5,7-trihydroxy-6,8-diiodochromen-4-one
MW: 679.925290 g/mol | MF: C15H7I3O7
141: CID: 11347622
CID11347622; 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(hydroxymethyl)chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(hydroxymethyl)chromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
142: CID: 18542127
IUPAC: 2-(2,3-dihydroxyphenyl)-7-methoxychromen-4-one
MW: 284.263480 g/mol | MF: C16H12O5
143: CID: 21725618
IUPAC: [2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxochromen-7-yl] sulfate
MW: 365.291560 g/mol | MF: C15H9O9S-
144: CID: 22138200
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(2,2,2-trihydroxyethyl)chromen-4-one
MW: 362.287660 g/mol | MF: C17H14O9
145: CID: 24721082
IUPAC: 3,6-dihydroxy-2-(2,4,5-trihydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
146: CID: 24721539
IUPAC: 2-(3,4-dihydroxyphenyl)-6,7-dihydroxychromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
147: CID: 25227000
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(methoxymethyl)chromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
148: CID: 44610309
IUPAC: 2-(3,4-dihydroxyphenyl)-5-ethoxy-7-hydroxychromen-4-one
MW: 314.289460 g/mol | MF: C17H14O6
149: CID: 44610477
IUPAC: 2-(3,4-dihydroxyphenyl)-7-ethoxy-5-hydroxychromen-4-one
MW: 314.289460 g/mol | MF: C17H14O6
150: CID: 25030204
IUPAC: 7-hydroxy-5-methoxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
151: CID: 25189611
IUPAC: 2-(3-fluoro-4,5-dihydroxyphenyl)-5,7-dihydroxychromen-4-one
MW: 304.226763 g/mol | MF: C15H9FO6
152: CID: 6477683
AIDS154806; CHEBI:480360; AIDS-154806
IUPAC: 2-[(E)-2-(3,4-dihydroxyphenyl)ethenyl]-5-hydroxychromen-4-one
MW: 296.274180 g/mol | MF: C17H12O5
153: CID: 9860659
CID9860659; 3,5,7-trihydroxy-2-(3-hydroxyphenyl)chromen-4-one
IUPAC: 3,5,7-trihydroxy-2-(3-hydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
154: CID: 632128
CHEBI:222167; CID632128; LMPK12112763
IUPAC: 2-(3-hydroxy-4-methoxyphenyl)-3,5,7-trimethoxychromen-4-one
MW: 358.342020 g/mol | MF: C19H18O7
155: CID: 5280631
Quercetin 3,3’,7-trissulfate; CHEBI:16557; LMPK12112310
IUPAC: [2-hydroxy-5-(5-hydroxy-4-oxo-3,7-disulfooxychromen-2-yl)phenyl] hydrogen sulfate
MW: 542.425300 g/mol | MF: C15H10O16S3
156: CID: 5280632
Quercetin 3,4’,7-trissulfate; CHEBI:28167; LMPK12112311
IUPAC: [2-hydroxy-4-(5-hydroxy-4-oxo-3,7-disulfooxychromen-2-yl)phenyl] hydrogen sulfate
MW: 542.425300 g/mol | MF: C15H10O16S3
157: CID: 5280682
Ayanin; 3,7,4’-Tri-O-methylquercetin; 3,7,4’-trimethylquercetin
IUPAC: 5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-3,7-dimethoxychromen-4-one
MW: 344.315440 g/mol | MF: C18H16O7
Tested in BioAssays: All: 59, Active: 0
158: CID: 5281677
Pachypodol; CHEBI:373037; NSC 168805
IUPAC: 5-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxychromen-4-one
MW: 344.315440 g/mol | MF: C18H16O7
159: CID: 5320848
CID5320848; 5-hydroxy-2-(4-hydroxy-3-sulfinatooxy-phenyl)-7-methoxy-4-oxo-3-sulfinatooxy-chromene
IUPAC: [2-hydroxy-5-(5-hydroxy-7-methoxy-4-oxo-3-sulfinatooxychromen-2-yl)phenyl] sulfite
MW: 442.374000 g/mol | MF: C16H10O11S2-2
160: CID: 5400219
Oprea1_158180; Oprea1_711058; MolPort-001-836-336
IUPAC: 7,8-dihydroxy-2-methyl-3-phenoxychromen-4-one
MW: 284.263480 g/mol | MF: C16H12O5
161: CID: 5482937
Quercetin Analogs; AIDS114005; AIDS-114005
IUPAC: [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl] acetate
MW: 344.272380 g/mol | MF: C17H12O8
162: CID: 5492759
Potassium quercetin phosphate; CID5492759; LS-39610
IUPAC: potassium; 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one; hydrogen phosphate
MW: 437.313301 g/mol | MF: C15H11KO11P-
163: CID: 6105183
Oprea1_065446; Oprea1_827089; CID6105183
IUPAC: 7,8-dihydroxy-3-phenoxychromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
164: CID: 6481478
AIDS337573; MolPort-000-165-393; AIDS-337573
IUPAC: 5,6,7-trihydroxy-3-methoxy-2-(4-methoxyphenyl)chromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
165: CID: 9818879
CHEBI:303768; CID9818879; 2-(3,4-Dihydroxy-phenyl)-7-hydroxy-3-(2-hydroxy-ethoxy)-chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-7-hydroxy-3-(2-hydroxyethoxy)chromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
166: CID: 10473561
CID10473561; [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxo-chromen-3-yl] Propanoate
IUPAC: [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl] propanoate
MW: 358.298960 g/mol | MF: C18H14O8
167: CID: 10807373
LMPK12111581; CID10807373; 3-hydroxy-2-(4-hydroxy-3,5-dimethoxy-phenyl)-7-methoxy-chromen-4-one
IUPAC: 3-hydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-7-methoxychromen-4-one
MW: 344.315440 g/mol | MF: C18H16O7
168: CID: 11834044
LMPK12112862; CID11834044; 5,6,7-trihydroxy-2-(4-hydroxyphenyl)-3-methoxy-chromen-4-one
IUPAC: 5,6,7-trihydroxy-2-(4-hydroxyphenyl)-3-methoxychromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
169: CID: 13942543
CHEBI:405386; LMPK12112755; 2-(4-Hydroxy-3-methoxy-phenyl)-3,5,7-trimethoxy-chromen-4-one
IUPAC: 2-(4-hydroxy-3-methoxyphenyl)-3,5,7-trimethoxychromen-4-one
MW: 358.342020 g/mol | MF: C19H18O7
170: CID: 14079475
LMPK12111600
IUPAC: 3,7-dihydroxy-8-methoxy-2-phenylchromen-4-one
MW: 284.263480 g/mol | MF: C16H12O5
171: CID: 14162697
CHEBI:405173; LMPK12112753; 7-Hydroxy-2-(4-hydroxy-3-methoxy-phenyl)-3,5-dimethoxy-chromen-4-one
IUPAC: 7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,5-dimethoxychromen-4-one
MW: 344.315440 g/mol | MF: C18H16O7
172: CID: 18372853
IUPAC: 2-(3,4-dihydroxyphenyl)-3,8-dihydroxy-7-methoxychromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
173: CID: 19890110
IUPAC: 3-hydroxy-2-(2-hydroxy-3,4-dimethoxyphenyl)-5,7-dimethoxychromen-4-one
MW: 374.341420 g/mol | MF: C19H18O8
174: CID: 20159736
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(2-hydroxyethoxy)chromen-4-one
MW: 346.288260 g/mol | MF: C17H14O8
175: CID: 20833257
IUPAC: [2-hydroxy-5-(3,5,7-trihydroxy-4-oxochromen-2-yl)phenyl] dihydrogen phosphate
MW: 382.215601 g/mol | MF: C15H11O10P
176: CID: 20981198
IUPAC: potassium 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one phosphate
MW: 436.305361 g/mol | MF: C15H10KO11P-2
177: CID: 22138197
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(2,2,2-trihydroxyethoxy)chromen-4-one
MW: 378.287060 g/mol | MF: C17H14O10
178: CID: 25183346
IUPAC: [2-hydroxy-4-(3,5,7-trihydroxy-4-oxochromen-2-yl)phenyl] dihydrogen phosphate
MW: 382.215601 g/mol | MF: C15H11O10P
179: CID: 44258703
LMPK12111607
IUPAC: 2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-8-methoxychromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
180: CID: 44258706
LMPK12111610
IUPAC: 3,7,8-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one
MW: 316.262280 g/mol | MF: C16H12O7
181: CID: 44259678
LMPK12112722
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-methoxy-6-methylchromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
182: CID: 44259679
LMPK12112723
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-methoxy-8-methylchromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
183: CID: 44594804
IUPAC: [2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4-oxochromen-3-yl] dihydrogen phosphate
MW: 382.215601 g/mol | MF: C15H11O10P
184: CID: 5281953
Syringetin; 3’,5’-O-Dimethylmyricetin; CHEBI:18215
IUPAC: 3,5,7-trihydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)chromen-4-one
MW: 346.288260 g/mol | MF: C17H14O8
185: CID: 5282154
Laricitrin; 3’-O-Methylmyricetin; LMPK12112482
IUPAC: 2-(3,4-dihydroxy-5-methoxyphenyl)-3,5,7-trihydroxychromen-4-one
MW: 332.261680 g/mol | MF: C16H12O8
186: CID: 5315126
Uralenol; CHEBI:288124; LMPK12112286
IUPAC: 2-[3,4-dihydroxy-5-(3-methylbut-2-enyl)phenyl]-3,5,7-trihydroxychromen-4-one
MW: 370.352720 g/mol | MF: C20H18O7
187: CID: 10343070
Broussonol E; CHEBI:565773; LMPK12112289
IUPAC: 2-[3,4-dihydroxy-5-(3-methylbut-2-enyl)phenyl]-3,5,7-trihydroxy-6-(3-methylbut-2-enyl)chromen-4-one
MW: 438.469740 g/mol | MF: C25H26O7
188: CID: 10359384
mearnsetin; CHEBI:583367; LMPK12112506
IUPAC: 2-(3,5-dihydroxy-4-methoxyphenyl)-3,5,7-trihydroxychromen-4-one
MW: 332.261680 g/mol | MF: C16H12O8
189: CID: 10365850
Broussonol D; CHEBI:565772; LMPK12112290
IUPAC: 2-[3,4-dihydroxy-5-(3-methylbut-2-enyl)phenyl]-3,5,7-trihydroxy-8-(3-methylbut-2-enyl)chromen-4-one
MW: 438.469740 g/mol | MF: C25H26O7
190: CID: 12314325
LMPK12112469
IUPAC: 3,5,7-trihydroxy-6-methyl-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 332.261680 g/mol | MF: C16H12O8
191: CID: 15559735
LMPK12113272
IUPAC: 3,5,7,8-tetrahydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 334.234500 g/mol | MF: C15H10O9
192: CID: 21676176
quercetin 3, 7, 4-trisulphate; quercetin 3, 7, 4’-trisulphate; CPD-10893
IUPAC: [2-hydroxy-4-(5-hydroxy-4-oxo-3,7-disulfonatooxychromen-2-yl)phenyl] sulfate
MW: 539.401480 g/mol | MF: C15H7O16S3-3
193: CID: 21676177
Quercetin 3,3’,7-trissulfate; QUERCETIN-337-TRISSULFATE
IUPAC: [2-hydroxy-5-(5-hydroxy-4-oxo-3,7-disulfonatooxychromen-2-yl)phenyl] sulfate
MW: 539.401480 g/mol | MF: C15H7O16S3-3
194: CID: 22507435
IUPAC: 3,5,7-trimethoxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
MW: 360.314840 g/mol | MF: C18H16O8
195: CID: 25202456
Syringetin
IUPAC: 5,7-dihydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-4-oxochromen-3-olate
MW: 345.280320 g/mol | MF: C17H13O8-
196: CID: 25203006
Laricitrin; CPD-8605
IUPAC: 2-hydroxy-6-methoxy-4-(3,5,7-trihydroxy-4-oxochromen-2-yl)phenolate
MW: 331.253740 g/mol | MF: C16H11O8-
197: CID: 44259511
LMPK12112509
IUPAC: 3,5,7-trihydroxy-2-(3-hydroxy-4,5-dimethoxyphenyl)chromen-4-one
MW: 346.288260 g/mol | MF: C17H14O8
198: CID: 44259638
LMPK12112666
IUPAC: 2-(3,5-dihydroxy-4-methoxyphenyl)-3,5-dihydroxy-7-methoxychromen-4-one
MW: 346.288260 g/mol | MF: C17H14O8
199: CID: 96506
Nortangeretin; MLS000736839; CHEBI:493043
IUPAC: 5,6,7,8-tetrahydroxy-2-(4-hydroxyphenyl)chromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
Tested in BioAssays: All: 182, Active: 17
200: CID: 797370
Oprea1_264669; Oprea1_552685; MolPort-001-831-555
IUPAC: 2-phenoxy-1-(2,3,4-trihydroxyphenyl)ethanone
MW: 260.242080 g/mol | MF: C14H12O5
201: CID: 5280666
Chrysoeriol; Chryseriol; 3’-Methoxyapigenin
IUPAC: 5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
Tested in BioAssays: All: 261, Active: 6
202: CID: 5281612
Diosmetin; 4’-Methylluteolin; Luteolin 4’-methyl ether
IUPAC: 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
Tested in BioAssays: All: 24, Active: 2
203: CID: 5281648
Hypolaetin; 8-Hydroxyluteolin; CHEBI:5837
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7,8-trihydroxychromen-4-one
MW: 302.235700 g/mol | MF: C15H10O7
204: CID: 5281665
Isoscutellarein; 8-Hydroxyapigenin; LMPK12111361
IUPAC: 5,7,8-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
205: CID: 5281674
Norwogonin; nor-wogonin; 5,7,8-Trihydroxyflavone
IUPAC: 5,7,8-trihydroxy-2-phenylchromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
Tested in BioAssays: All: 5, Active: 1
206: CID: 5320496
Pilloin; Luteolin 7,4’-dimethyl ether; CHEBI:583719
IUPAC: 5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-methoxychromen-4-one
MW: 314.289460 g/mol | MF: C17H14O6
207: CID: 5464381
Velutin; Flavonoid; Luteolin 7,3’-dimethyl ether
IUPAC: 5-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-7-methoxychromen-4-one
MW: 314.289460 g/mol | MF: C17H14O6
208: CID: 5487855
sec-Butyl benzoate; 3’,4’-Dimethoxyquercetin; LMPK12112411
IUPAC: 2-(3,4-dimethoxyphenyl)-3,5,7-trihydroxychromen-4-one
MW: 330.288860 g/mol | MF: C17H14O7
209: CID: 10357421
CID10357421; 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methyl-chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7-methylchromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
210: CID: 11474580
CID11474580; 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(3-methylbut-2-enoxymethyl)chromen-4-one
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-(3-methylbut-2-enoxymethyl)chromen-4-one
MW: 384.379300 g/mol | MF: C21H20O7
211: CID: 13964547
CHEBI:405387; LMPK12110968; 7-Hydroxy-2-(3-hydroxy-4-methoxy-phenyl)-5-methoxy-chromen-4-one
IUPAC: 7-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-5-methoxychromen-4-one
MW: 314.289460 g/mol | MF: C17H14O6
212: CID: 13964549
Chrysoeriol 5-methyl ether; LMPK12110967
IUPAC: 7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-methoxychromen-4-one
MW: 314.289460 g/mol | MF: C17H14O6
213: CID: 14016780
LMPK12110734
IUPAC: [2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxochromen-7-yl] hydrogen sulfate
MW: 366.299500 g/mol | MF: C15H10O9S
214: CID: 15293760
LMPK12110728
IUPAC: 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-6-methylchromen-4-one
MW: 300.262880 g/mol | MF: C16H12O6
215: CID: 21725619
IUPAC: [2-hydroxy-4-(5-hydroxy-4-oxo-7-sulfonatooxychromen-2-yl)phenyl] sulfate
MW: 444.346820 g/mol | MF: C15H8O12S2-2
216: CID: 44258151
LMPK12110735
IUPAC: [5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxyphenyl] hydrogen sulfate
MW: 366.299500 g/mol | MF: C15H10O9S
217: CID: 44258152
LMPK12110736
IUPAC: [4-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxyphenyl] hydrogen sulfate
MW: 366.299500 g/mol | MF: C15H10O9S
218: CID: 44608109
IUPAC: 7-butoxy-2-(3,4-dihydroxyphenyl)-5-hydroxychromen-4-one
MW: 342.342620 g/mol | MF: C19H18O6
219: CID: 44610310
IUPAC: 2-(3,4-dihydroxyphenyl)-7-hydroxy-5-octoxychromen-4-one
MW: 398.448940 g/mol | MF: C23H26O6
220: CID: 44610311
IUPAC: 2-(3,4-dihydroxyphenyl)-7-hydroxy-5-propoxychromen-4-one
MW: 328.316040 g/mol | MF: C18H16O6
221: CID: 44610312
IUPAC: 5-decoxy-2-(3,4-dihydroxyphenyl)-7-hydroxychromen-4-one
MW: 426.502100 g/mol | MF: C25H30O6
222: CID: 44610313
IUPAC: 2-(3,4-dihydroxyphenyl)-5-hexoxy-7-hydroxychromen-4-one
MW: 370.395780 g/mol | MF: C21H22O6
223: CID: 44610474
IUPAC: 5-butoxy-2-(3,4-dihydroxyphenyl)-7-hydroxychromen-4-one
MW: 342.342620 g/mol | MF: C19H18O6
224: CID: 1880
7,8-dihydroxyflavone; FLAVONE; 7,8-Dihydroxy-flavone
IUPAC: 7,8-dihydroxy-2-phenylchromen-4-one
MW: 254.237500 g/mol | MF: C15H10O4
Tested in BioAssays: All: 92, Active: 8
225: CID: 676309
TNP00055; CHEBI:490243; CID676309
IUPAC: 7,8-dihydroxy-2-(2-hydroxyphenyl)chromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
Tested in BioAssays: All: 80, Active: 18
226: CID: 688853
7,8,4-trihydroxyflavone; CHEBI:246131; ZINC00057915
IUPAC: 7,8-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
227: CID: 9814421
CID9814421; 2-(2,4-dihydroxyphenyl)-7,8-dihydroxy-chromen-4-one
IUPAC: 2-(2,4-dihydroxyphenyl)-7,8-dihydroxychromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
228: CID: 18778789
IUPAC: (2E)-2-[(3,4-dihydroxyphenyl)methylidene]-7-hydroxychromen-4-one
MW: 284.263480 g/mol | MF: C16H12O5
229: CID: 17840570
IUPAC: (3,5,6-trihydroxy-2-phenylchromen-4-ylidene)oxidanium
MW: 271.244840 g/mol | MF: C15H11O5+
230: CID: 17840571
IUPAC: 3,5,6-trihydroxy-2-phenylchromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
231: CID: 23064865
IUPAC: 2-(2,3,4,6-tetrahydroxyphenyl)chromen-4-one
MW: 286.236300 g/mol | MF: C15H10O6
232: CID: 5393165
ZINC00057845; CID5393165
IUPAC: 3,7-dihydroxy-2-(3-hydroxyphenyl)chromen-4-one
MW: 270.236900 g/mol | MF: C15H10O5
233: CID: 20977459
IUPAC: [3,5,7-trihydroxy-2-(3-hydroxyphenyl)chromen-4-ylidene]oxidanium chloride
MW: 322.697240 g/mol | MF: C15H11ClO6
List of analogs with quercetin similarity (tanimoto coefficient) of 95% or more
1: CID: 5280343
quercetin; Sophoretin; Meletin
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
Tested in BioAssays: All: 281, Active: 55
Antioxidants more
2: CID: 20670067
IUPAC: actinium; 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one
MW: 1437.374435 g / mol | MF: C15H10Ac5O7
3: CID: 5281614
Fisetin; Cotinin; Superfustel
IUPAC: 2- (3,4-dihydroxyphenyl) -3,7-dihydroxychromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
Tested in BioAssays: All: 174, Active: 28
4: CID: 5281692
Robinetin; Norkanugin; 5-Deoxymyricetin
IUPAC: 3,7-dihydroxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
Tested in BioAssays: All: 24, Active: 2
5: CID: 5284452
Quercetin dihydrate; quercetin; Quercetine dihydrate
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one dihydrate
MW: 338.266260 g / mol | MF: C15H14O9
Tested in BioAssays: All: 98, Active: 12
Antioxidants more
6: CID: 10818722
CID10818722; [2,3-dihydroxy-6- (3,5,7-trihydroxy-4-oxo-chromen-2-yl) phenyl] thallium
IUPAC: [2,3-dihydroxy-6- (3,5,7-trihydroxy-4-oxochromen-2-yl) phenyl] thallium
MW: 505.611060 g / mol | MF: C15H9O7Tl
7: CID: 16212154
Quercetin hydrate; MLS001074343; MLS002153851
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one hydrate
MW: 320.250980 g / mol | MF: C15H12O8
Tested in BioAssays: All: 132, Active: 14
8: CID: 16213065
Fisetin; 5-Deoxyquercetin; Natural Brown- 1
IUPAC: 2- (3,4-dihydroxyphenyl) -3,7-dihydroxychromen-4-one hydrate
MW: 304.251580 g / mol | MF: C15H12O7
9: CID: 24187083
NSC58588; 7255-55-2
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one; zirconium
MW: 393.459700 g / mol | MF: C15H10O7Zr
Tested in BioAssays: All: 1, Active: 0
10: CID: 25031947
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one; selenium
MW: 381.195700 g / mol | MF: C15H10O7Se
11: CID: 12305312
IUPAC: 6,8-dideuterio-3,5,7-trihydroxy-2- (2,3,6-trideuterio-4,5-dihydroxyphenyl) chromen-4-one
MW: 307.266509 g / mol | MF: C15H10O7
12: CID: 21600688
IUPAC: 3,5,7-trihydroxy-2- (2,3,6-trideuterio-4,5-dihydroxyphenyl) chromen-4-one
MW: 305.254185 g / mol | MF: C15H10O7
13: CID: 23105025
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5-dihydroperoxy-7-hydroxychromen-4-one
MW: 334.234500 g / mol | MF: C15H10O9
14: CID: 5281672
myricetin; Cannabiscetin; Myricetol
IUPAC: 3,5,7-trihydroxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 318.235100 g / mol | MF: C15H10O8
Tested in BioAssays: All: 277, Active: 48
15: CID: 12309893
IUPAC: 8-deuterio-3,7-dihydroxy-2- (2,3,6-trideuterio-4,5-dihydroxyphenyl) chromen-4-one
MW: 290.260947 g / mol | MF: C15H10O6
16: CID: 25201643
myricetin
IUPAC: 2,6-dihydroxy-4- (3,5,7-trihydroxy-4-oxochromen-2-yl) phenolate
MW: 317.227160 g / mol | MF: C15H9O8-
17: CID: 5280445
luteolin; Luteoline; Luteolol
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxychromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
Tested in BioAssays: All: 258, Active: 41
18: CID: 5321864
5,7,2 ', 3'-Tetrahydroxyflavone;LMPK12110137; CID5321864
IUPAC: 2- (2,3-dihydroxyphenyl) -5,7-dihydroxychromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
19: CID: 18471844
ZINC14644152
IUPAC: 5,7-dihydroxy-2- (2,3,4-trihydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
20: CID: 22339062
IUPAC: 3,5-dihydroxy-2- (2,3,4-trihydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
21: CID: 25201972
luteolin; 5734-TETRAHYDROXYFLAVONE; 3 ', 4', 5,7-Tetrahydroxyflavone
IUPAC: 4- (5,7-dihydroxy-4-oxochromen-2-yl) -2-hydroxyphenolate
MW: 285.228360 g / mol | MF: C15H9O6-
22: CID: 26034
5,7-Di-O-methylquercetin; BRN 0344074; CID26034
IUPAC: 2- (3,4-dihydroxyphenyl) -3-hydroxy-5,7-dimethoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
23: CID: 5281604
Azaleatin; 5-O-Methylquercetin; Quercetin 5-methyl ether
IUPAC: 2- (3,4-dihydroxyphenyl) -3,7-dihydroxy-5-methoxychromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
24: CID: 5281638
6-Hydroxykaempferol; CHEBI: 563476; LMPK12112860
IUPAC: 3,5,6,7-tetrahydroxy-2- (4-hydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
25: CID: 5281691
Rhamnetin; 7-Methoxyquercetin; 7-Methylquercetin
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5-dihydroxy-7-methoxychromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
Tested in BioAssays: All: 117, Active: 6
26: CID: 10598612
CID10598612; 2- (3,4-dihydroxy-2-iodo-phenyl) -3,5,7-trihydroxy-chromen-4-one
IUPAC: 2- (3,4-dihydroxy-2-iodophenyl) -3,5,7-trihydroxychromen-4-one
MW: 428.132230 g / mol | MF: C15H9IO7
27: CID: 15233950
LMPK12112802
IUPAC: 3,5,6,7-tetrahydroxy-2-phenylchromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
28: CID: 17840574
IUPAC: (3,5,6,7-tetrahydroxy-2-phenylchromen-4-ylidene) oxidanium
MW: 287.244240 g / mol | MF: C15H11O6 +
29: CID: 24721675
IUPAC: 3,7-dihydroxy-2- (2,4,5-trihydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
30: CID: 25205335
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one; platinum (4+); dichloride
MW: 568.219700 g / mol | MF: C15H10Cl2O7Pt + 2
31: CID: 25206803
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one; platinum (4+); chloride; hydrochloride
MW: 569.227640 g / mol | MF: C15H11Cl2O7Pt + 3
32: CID: 5322065
7,3 ', 4'-Trihydroxyflavone;3', 4 ', 7-Trihydroxyflavone; BRN 0253031
IUPAC: 2- (3,4-dihydroxyphenyl) -7-hydroxychromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
33: CID: 5393164
7,3,4,5-tetrahydroxyflavone; CHEBI: 519698; LMPK12110051
IUPAC: 7-hydroxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
34: CID: 10517292
CID10517292; 3-hydroxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
IUPAC: 3-hydroxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
35: CID: 16662883
IUPAC: 2- (2,3-dihydroxyphenyl) -7-hydroxychromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
36: CID: 21158518
IUPAC: 7-hydroxy-2- (2,3,4-trihydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
37: CID: 5281701
Tricetin; Spectrum_001591; SpecPlus_000826
IUPAC: 5,7-dihydroxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
Tested in BioAssays: All: 63, Active: 9
38: CID: 12359024
IUPAC: 3,6,8-trideuterio-5,7-dihydroxy-2- (2,3,6-trideuterio-4,5-dihydroxyphenyl) chromen-4-one
MW: 292.273271 g / mol | MF: C15H10O6
39: CID: 12359025
IUPAC: 3-deuterio-5,7-dihydroxy-2- (2,3,6-trideuterio-4,5-dihydroxyphenyl) chromen-4-one
MW: 290.260947 g / mol | MF: C15H10O6
40: CID: 627207
CHEBI: 347700; CID627207; 3-Hydroxy-2- (3,4-dihydroxyphenyl) -7-methoxy-4H-chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -3-hydroxy-7-methoxychromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
41: CID: 5280417
3,7-Di-O-methylquercetin; CHEBI: 18010; MolPort-001-742-139
IUPAC: 2- (3,4-dihydroxyphenyl) -5-hydroxy-3,7-dimethoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
42: CID: 5280681
3-O-Methylquercetin; 3-Methoxy quercetin; Quercetin-3-methylether
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3-methoxychromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
Tested in BioAssays: All: 234, Active: 11
43: CID: 5281680
Quercetagetin; 6-Hydroxyquercetin; CHEBI: 202888
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,6,7-tetrahydroxychromen-4-one
MW: 318.235100 g / mol | MF: C15H10O8
44: CID: 5319492
Flavone der .; AIDS071769; CHEBI: 219000
IUPAC: 2- (3,4-dihydroxyphenyl) -3,6,7-trihydroxychromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
45: CID: 5489501
3,5-Di-O-methylquercetin; LMPK12112730; CID5489501
IUPAC: 2- (3,4-dihydroxyphenyl) -7-hydroxy-3,5-dimethoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
46: CID: 10516160
CID10516160; 3,7,8-trihydroxy-2-phenyl-chromen-4-one
IUPAC: 3,7,8-trihydroxy-2-phenylchromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
47: CID: 15560442
LMPK12111605
IUPAC: 2- (3,4-dihydroxyphenyl) -3,7,8-trihydroxychromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
48: CID: 21676161
IUPAC: [2-hydroxy-5- (3,5,7-trihydroxy-4-oxochromen-2-yl) phenyl] sulfate
MW: 381.290960 g / mol | MF: C15H9O10S-
49: CID: 21676163
IUPAC: [2- (3,4-dihydroxyphenyl) -3,5-dihydroxy-4-oxochromen-7-yl] sulfate
MW: 381.290960 g / mol | MF: C15H9O10S-
50: CID: 21676164
IUPAC: [2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-4-oxochromen-3-yl] sulfate
MW: 381.290960 g / mol | MF: C15H9O10S-
51: CID: 22239065
LMPK12111601; ZINC12359395
IUPAC: 3,7,8-trihydroxy-2- (4-hydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
52: CID: 24721178
IUPAC: 3,7,8-trihydroxy-2- (2-hydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
53: CID: 25202270
3-methoxyluteolin; 3-O-Methylquercetin; 3 ', 4', 5,7-Tetrahydroxy-3-methoxyflavone
IUPAC: 4- (5,7-dihydroxy-3-methoxy-4-oxochromen-2-yl) -2-hydroxyphenolate
MW: 315.254340 g / mol | MF: C16H11O7-
54: CID: 25203115
Quercetin 3-sulfate; CPD-1822
IUPAC: [5,7-dihydroxy-2- (3-hydroxy-4-oxidophenyl) -4-oxochromen-3-yl] sulfate
MW: 380.283020 g / mol | MF: C15H8O10S-2
55: CID: 25206804
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one; platinum (4+); tetrachloride
MW: 639.125700 g / mol | MF: C15H10Cl4O7Pt
56: CID: 16113029
LMPK12112522
IUPAC: 3,5,7-trihydroxy-2- (2,4,5-trihydroxyphenyl) chromen-4-one
MW: 318.235100 g / mol | MF: C15H10O8
57: CID: 15661823
ZINC04349582
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3-methylchromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
58: CID: 6477685
AIDS154808; CHEBI: 480357; AIDS-154808
IUPAC: 2-[(E) -2- (3,4-dihydroxyphenyl) ethenyl] -5,7-dihydroxychromen-4-one
MW: 312.273580 g / mol | MF: C17H12O6
59: CID: 88281
5,3 ', 4'-Trihydroxyflavone;TNP00056; CHEBI: 490257
IUPAC: 2- (3,4-dihydroxyphenyl) -5-hydroxychromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
Tested in BioAssays: All: 81, Active: 10
60: CID: 17851159
IUPAC: 5-hydroxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
61: CID: 147651
Quercetin trimethyl ether; ZINC00338058; CID147651
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trimethoxychromen-4-one
MW: 344.315440 g / mol | MF: C18H16O7
62: CID: 5280362
Quercetin 3-sulfate; quercetin 3- (hydrogen sulfate); CHEBI: 17730
IUPAC: [2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-4-oxochromen-3-yl] hydrogen sulfate
MW: 382.298900 g / mol | MF: C15H10O10S
63: CID: 5280544
Herbacetin; 8-Hydroxykaempferol; LMPK12113149
IUPAC: 3,5,7,8-tetrahydroxy-2- (4-hydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
64: CID: 5281654
Isorhamnetin; 3-Methylquercetin; Isorhamnetol
IUPAC: 3,5,7-trihydroxy-2- (4-hydroxy-3-methoxyphenyl) chromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
Tested in BioAssays: All: 18, Active: 2
65: CID: 5281679
Pinoquercetin; 6-C-Methylquercetin; LMPK12112292
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-6-methylchromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
66: CID: 5281699
Tamarixetin; 4'-O-Methylquercetin; Quercetin 4'-methyl ether
IUPAC: 3,5,7-trihydroxy-2- (3-hydroxy-4-methoxyphenyl) chromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
67: CID: 5320287
Ombuin; 4 ', 7-Dimethylquercetin; 7,4'-Di-O-methylquercetin
IUPAC: 3,5-dihydroxy-2- (3-hydroxy-4-methoxyphenyl) -7-methoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
68: CID: 5320945
Rhamnazin; 3 ', 7-Dimethylquercetin; 7,3'-Di-O-methylquercetin
IUPAC: 3,5-dihydroxy-2- (4-hydroxy-3-methoxyphenyl) -7-methoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
Tested in BioAssays: All: 61, Active: 1
69: CID: 5362017
8-Hydroxygalangin; 3,5,7,8-Tetrahydroxyflavone; BRN 0295943
IUPAC: 3,5,7,8-tetrahydroxy-2-phenylchromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
70: CID: 5388949
nchembio718-comp16; ZINC04731234; CID5388949
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-8-methylchromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
71: CID: 9839293
CHEBI: 304347; LMPK12111567; CID9839293
IUPAC: 2- (3,4-dihydroxyphenyl) -7-hydroxy-3-methoxychromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
72: CID: 10022760
LMPK12112305; CID10022760; 2- (3,4-dihydroxyphenyl) -3,5-dihydroxy-4-oxo-7-sulfooxy-chromene
IUPAC: [2- (3,4-dihydroxyphenyl) -3,5-dihydroxy-4-oxochromen-7-yl] hydrogen sulfate
MW: 382.298900 g / mol | MF: C15H10O10S
73: CID: 11012936
CID11012936; 3,5-dihydroxy-2- (3-hydroxy-2-methoxy-phenyl) -7-methoxy-chromen-4-one
IUPAC: 3,5-dihydroxy-2- (3-hydroxy-2-methoxyphenyl) -7-methoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
74: CID: 14162696
LMPK12112547
IUPAC: 3,7-dihydroxy-2- (4-hydroxy-3-methoxyphenyl) -5-methoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
75: CID: 15227607
LMPK12112548
IUPAC: 3,7-dihydroxy-2- (3-hydroxy-4-methoxyphenyl) -5-methoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
76: CID: 20504452
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one; methoxymethane
MW: 348.304140 g / mol | MF: C17H16O8
77: CID: 21676162
LMPK12112306
IUPAC: [2-hydroxy-5- (3,5,7-trihydroxy-4-oxochromen-2-yl) phenyl] hydrogen sulfate
MW: 382.298900 g / mol | MF: C15H10O10S
78: CID: 21676167
IUPAC: [5,7-dihydroxy-2- (4-hydroxy-3-sulfonatooxyphenyl) -4-oxochromen-3-yl] sulfate
MW: 460.346220 g / mol | MF: C15H8O13S2-2
79: CID: 21676170
IUPAC: [5,7-dihydroxy-2- (3-hydroxy-4-sulfonatooxyphenyl) -4-oxochromen-3-yl] sulfate
MW: 460.346220 g / mol | MF: C15H8O13S2-2
80: CID: 21676173
IUPAC: [3,5-dihydroxy-2- (3-hydroxy-4-sulfonatooxyphenyl) -4-oxochromen-7-yl] sulfate
MW: 460.346220 g / mol | MF: C15H8O13S2-2
81: CID: 23670118
CHEBI: 604112; potassium 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-4-oxo-4H-chromen-3-yl sulfate
IUPAC: potassium [2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-4-oxochromen-3-yl] sulfate
MW: 420.389260 g / mol | MF: C15H9KO10S
82: CID: 25164913
IUPAC: [2-hydroxy-4- (3,5,7-trihydroxy-4-oxochromen-2-yl) phenyl] hydrogen sulfate
MW: 382.298900 g / mol | MF: C15H10O10S
83: CID: 25202413
Isorhamnetin; 3-Methylquercetin; 3'-Methoxyquercetin
IUPAC: 5,7-dihydroxy-2- (4-hydroxy-3-methoxyphenyl) -4-oxochromen-3-olate
MW: 315.254340 g / mol | MF: C16H11O7-
84: CID: 25206967
IUPAC: azane; 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one; platinum (2+); dichloride
MW: 585.250220 g / mol | MF: C15H13Cl2NO7Pt
85: CID: 44472542
IUPAC: azane; 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one; platinum
MW: 531.374740 g / mol | MF: C15H16N2O7Pt
86: CID: 5319731
5-Methylmyricetin; LMPK12112555; CID5319731
IUPAC: 3,7-dihydroxy-5-methoxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 332.261680 g / mol | MF: C16H12O8
87: CID: 14376433
LMPK12113049
IUPAC: 3,5,6,7-tetrahydroxy-2- (2,3,4-trihydroxyphenyl) chromen-4-one
MW: 334.234500 g / mol | MF: C15H10O9
88: CID: 44259636
LMPK12112664
IUPAC: 3,5-dihydroxy-7-methoxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 332.261680 g / mol | MF: C16H12O8
89: CID: 5280616
2'-hydroxypseudobaptigenin;CID5280616; C03662
IUPAC: 7-hydroxy-2- (2,3,4,5-tetrahydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
90: CID: 5281605
baicalein; 5,6,7-Trihydroxyflavone; Biacalein
IUPAC: 5,6,7-trihydroxy-2-phenylchromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
Tested in BioAssays: All: 120, Active: 30
Prostaglandin Antagonists more
91: CID: 5281642
6-Hydroxyluteolin; Demethylpedalitin; 6-OH-Luteolin
IUPAC: 2- (3,4-dihydroxyphenyl) -5,6,7-trihydroxychromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
92: CID: 5281697
Scutellarein; Isocarthamidin; Flavonoid
IUPAC: 5,6,7-trihydroxy-2- (4-hydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
93: CID: 5318214
Hydroxygenkwanin; 7-O-Methylluteolin; MEGxp0_000798
IUPAC: 2- (3,4-dihydroxyphenyl) -5-hydroxy-7-methoxychromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
94: CID: 5702782
baicalein; 5,6,7-Trihydroxyflavone; OR1525T
IUPAC: 5,6,7-trihydroxy-2-phenylchromen-4-one hydrate
MW: 288.252180 g / mol | MF: C15H12O6
Prostaglandin Antagonists more
95: CID: 13964548
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dimethoxychromen-4-one
MW: 314.289460 g / mol | MF: C17H14O6
96: CID: 13964550
LMPK12110965
IUPAC: 2- (3,4-dihydroxyphenyl) -7-hydroxy-5-methoxychromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
97: CID: 18372862
IUPAC: 2- (3,4-dihydroxyphenyl) -3-hydroxy-5-methoxychromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
98: CID: 5281649
Isoetin; LMPK12110940; 5,7,2 ', 4', 5'-Pentahydroxyflavone
IUPAC: 5,7-dihydroxy-2- (2,4,5-trihydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
99: CID: 6477684
AIDS154807; CHEBI: 480359; AIDS-154807
IUPAC: 2-[(E) -2- (3,4-dihydroxyphenyl) ethenyl] -7-hydroxychromen-4-one
MW: 296.274180 g / mol | MF: C17H12O5
100: CID: 10636768
CHEBI: 185726; CID10636768; 2- (3,4-Dihydroxy-benzyl) -7-hydroxy-chromen-4-one
IUPAC: 2-[(3,4-dihydroxyphenyl) methyl] -7-hydroxychromen-4-one
MW: 284.263480 g / mol | MF: C16H12O5
101: CID: 12417670
IUPAC: 2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
102: CID: 22507438
IUPAC: 2- (2,3,4-trihydroxyphenyl) chromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
103: CID: 628780
CID628780; 3-Hydroxy-2- (3-hydroxy-4-methoxyphenyl) -7-methoxy-4H-chromen-4-one
IUPAC: 3-hydroxy-2- (3-hydroxy-4-methoxyphenyl) -7-methoxychromen-4-one
MW: 314.289460 g / mol | MF: C17H14O6
104: CID: 4125009
CID4125009; 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-6,8-bis (3-methylbut-2-enyl) chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-6,8-bis (3-methylbut-2-enyl) chromen-4-one
MW: 438.469740 g / mol | MF: C25H26O7
105: CID: 5280402
Quercetin 3,3'-bissulfate; CHEBI: 17875; LMPK12112308
IUPAC: [5,7-dihydroxy-2- (4-hydroxy-3-sulfooxyphenyl) -4-oxochromen-3-yl] hydrogen sulfate
MW: 462.362100 g / mol | MF: C15H10O13S2
106: CID: 5280403
Quercetin 3,4'-bissulfate; CHEBI: 18030; LMPK12112309
IUPAC: [5,7-dihydroxy-2- (3-hydroxy-4-sulfooxyphenyl) -4-oxochromen-3-yl] hydrogen sulfate
MW: 462.362100 g / mol | MF: C15H10O13S2
107: CID: 5280647
Gossypetin; Articulatidin; Equisporol
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7,8-tetrahydroxychromen-4-one
MW: 318.235100 g / mol | MF: C15H10O8
Tested in BioAssays: All: 54, Active: 8
108: CID: 5316900
Quercetin der .; 3,3'-Dimethylquercetin;3,3'-Dimethoxyquercetin
IUPAC: 5,7-dihydroxy-2- (4-hydroxy-3-methoxyphenyl) -3-methoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
109: CID: 5378244
LMPK12111569; CID5378244; 3,7-Dihydroxy-2- (3-hydroxy-4-methoxyphenyl) -4H-chromen-4-one
IUPAC: 3,7-dihydroxy-2- (3-hydroxy-4-methoxyphenyl) chromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
110: CID: 5380905
ACon1_001466; CHEBI: 221146; MolPort-001-741-117
IUPAC: 5,7-dihydroxy-2- (3-hydroxy-4-methoxyphenyl) -3-methoxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
Tested in BioAssays: All: 1, Active: 0
111: CID: 5481966
Gancaonin P; AIDS095976; CHEBI: 565528
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-6- (3-methylbut-2-enyl) chromen-4-one
MW: 370.352720 g / mol | MF: C20H18O7
112: CID: 5482101
Geraldol; SPECTRUM1505149; BIDF1020
IUPAC: 3,7-dihydroxy-2- (4-hydroxy-3-methoxyphenyl) chromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
Tested in BioAssays: All: 52, Active: 3
113: CID: 6452329
M7HEQ; 7-O-beta-Hydroxyethylquercetin; 7-O- (beta-Hydroxyethyl) quercetin
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5-dihydroxy-7- (2-hydroxyethoxy) chromen-4-one
MW: 346.288260 g / mol | MF: C17H14O8
114: CID: 9799499
CHEBI: 420898; ZINC03918592; CID9799499
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-8- (3-methylbut-2-enyl) chromen-4-one
MW: 370.352720 g / mol | MF: C20H18O7
115: CID: 9949390
CHEBI: 303634; CID9949390; 2- (3,4-Dihydroxy-phenyl) -3-hydroxy-7- (2-hydroxy-ethoxy) -chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -3-hydroxy-7- (2-hydroxyethoxy) chromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
116: CID: 10004518
CID10004518; 3,5-dihydroxy-2- (3-hydroxy-4-sulfooxy-phenyl) -4-oxo-7-sulfooxy-chromene
IUPAC: [3,5-dihydroxy-2- (3-hydroxy-4-sulfooxyphenyl) -4-oxochromen-7-yl] hydrogen sulfate
MW: 462.362100 g / mol | MF: C15H10O13S2
117: CID: 10050405
CID10050405; 2- (3,4-dihydroxyphenyl) -7-dodecoxy-3,5-dihydroxy-chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -7-dodecoxy-3,5-dihydroxychromen-4-one
MW: 470.554660 g / mol | MF: C27H34O7
118: CID: 10895435
CHEBI: 565814; CID10895435; 5,7,3 ', 4'-tetrahydroxy-6-geranylflavono
IUPAC: 2- (3,4-dihydroxyphenyl) -6-[(2E) -3,7-dimethylocta-2,6-dienyl] -3,5,7-trihydroxychromen-4-one
MW: 438.469740 g / mol | MF: C25H26O7
119: CID: 12988287
LMPK12112307
IUPAC: [2- (3,4-dihydroxyphenyl) -5-hydroxy-4-oxo-3-sulfooxychromen-7-yl] hydrogen sulfate
MW: 462.362100 g / mol | MF: C15H10O13S2
120: CID: 15895793
LMPK12111579
IUPAC: 3,7-dihydroxy-2- (4-hydroxy-3,5-dimethoxyphenyl) chromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
121: CID: 17918606
IUPAC: 3,5,6,7,8-pentahydroxy-2- (2-hydroxyphenyl) chromen-4-one
MW: 318.235100 g / mol | MF: C15H10O8
122: CID: 21633676
LMPK12112866
IUPAC: 3,5,6,7-tetrahydroxy-2- (4-methoxyphenyl) chromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
123: CID: 23320229
IUPAC: 2- (3,4-dihydroxyphenyl) -3-ethoxy-7-hydroxychromen-4-one
MW: 314.289460 g / mol | MF: C17H14O6
124: CID: 24206515
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3-methoxychromen-4-one trihydrate
MW: 370.308120 g / mol | MF: C16H18O10
125: CID: 25201917
334578-HEXAHYDROXYFLAVONE; 3,3 ', 4', 5,7,8-Hexahydroxyflavone; 2- (3,4-dihydroxyphenyl) -3,5,7,8-tetrahydroxy-chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxy-4-oxochromen-8-olate
MW: 317.227160 g / mol | MF: C15H9O8-
126: CID: 44259330
LMPK12112314
IUPAC: [4- (3,5-dihydroxy-7-hydroxysulfonothioyloxy-4-oxochromen-2-yl) -2-hydroxyphenyl] hydrogen sulfate
MW: 478.427700 g / mol | MF: C15H10O12S3
127: CID: 44259518
LMPK12112520
IUPAC: 3,5,7-trihydroxy-2- (3-hydroxy-2,4-dimethoxyphenyl) chromen-4-one
MW: 346.288260 g / mol | MF: C17H14O8
128: CID: 44260065
LMPK12113327
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5,6,7,8-pentahydroxychromen-4-one
MW: 334.234500 g / mol | MF: C15H10O9
129: CID: 24721651
IUPAC: 5-hydroxy-3,7-dimethoxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 346.288260 g / mol | MF: C17H14O8
130: CID: 25087106
Peflavit; Pentahydroxyflavone; 54077-18-8
IUPAC: 3,5,6,7,8-pentahydroxy-2-phenylchromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
131: CID: 25202871
quercetin-3,4-bissulfate; quercetin-3,4'-bissulfate; QUERCETIN-34-BISSULFATE
IUPAC: [2-hydroxy-4- (7-hydroxy-5-oxido-4-oxo-3-sulfonatooxychromen-2-yl) phenyl] sulfate
MW: 459.338280 g / mol | MF: C15H7O13S2-3
132: CID: 44259709
LMPK12112779
IUPAC: 5,7-dihydroxy-3-methoxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 332.261680 g / mol | MF: C16H12O8
133: CID: 676310
TNP00054; CHEBI: 473681; CID676310
IUPAC: 7,8-dihydroxy-2- (3-hydroxyphenyl) chromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
Tested in BioAssays: All: 81, Active: 10
134: CID: 688798
7,8,3 ', 4'-tetrahydroxyflavone;3', 4 ', 7,8-Tetrahydroxyflavone; CHEBI: 473674
IUPAC: 2- (3,4-dihydroxyphenyl) -7,8-dihydroxychromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
135: CID: 5353357
6,7-dihydroxyflavone; 6,7-dihydroxyflavone; DivK1c_000421
IUPAC: 6,7-dihydroxy-2-phenylchromen-4-one
MW: 254.237500 g / mol | MF: C15H10O4
Tested in BioAssays: All: 86, Active: 5
136: CID: 5393155
ZINC00057757; CID5393155
IUPAC: 6,7-dihydroxy-2- (3-hydroxyphenyl) chromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
137: CID: 10355753
CHEBI: 576113; CID10355753; 6,7-dihydroxy-2- (4-hydroxyphenyl) chromen-4-one
IUPAC: 6,7-dihydroxy-2- (4-hydroxyphenyl) chromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
138: CID: 10493280
CHEBI: 303856; CID10493280; 2- (3,4-dihydroxyphenyl) -7-methoxy-chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -7-methoxychromen-4-one
MW: 284.263480 g / mol | MF: C16H12O5
139: CID: 10532672
CID10532672; 2- (3,4-dihydroxy-2-iodo-phenyl) -3,5,7-trihydroxy-6,8-diiodo-chromen-4-one
IUPAC: 2- (3,4-dihydroxy-2-iodanylphenyl) -3,5,7-trihydroxy-6,8-bis (iodanyl) chromen-4-one
MW: 691.930253 g / mol | MF: C15H7I3O7
140: CID: 10556475
CID10556475; 2- (3,4-dihydroxy-2-iodo-phenyl) -3,5,7-trihydroxy-6,8-diiodo-chromen-4-one
IUPAC: 2- (3,4-dihydroxy-2-iodophenyl) -3,5,7-trihydroxy-6,8-diiodochromen-4-one
MW: 679.925290 g / mol | MF: C15H7I3O7
141: CID: 11347622
CID11347622; 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3- (hydroxymethyl) chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3- (hydroxymethyl) chromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
142: CID: 18542127
IUPAC: 2- (2,3-dihydroxyphenyl) -7-methoxychromen-4-one
MW: 284.263480 g / mol | MF: C16H12O5
143: CID: 21725618
IUPAC: [2- (3,4-dihydroxyphenyl) -5-hydroxy-4-oxochromen-7-yl] sulfate
MW: 365.291560 g / mol | MF: C15H9O9S-
144: CID: 22138200
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3- (2,2,2-trihydroxyethyl) chromen-4-one
MW: 362.287660 g / mol | MF: C17H14O9
145: CID: 24721082
IUPAC: 3,6-dihydroxy-2- (2,4,5-trihydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
146: CID: 24721539
IUPAC: 2- (3,4-dihydroxyphenyl) -6,7-dihydroxychromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
147: CID: 25227000
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3- (methoxymethyl) chromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
148: CID: 44610309
IUPAC: 2- (3,4-dihydroxyphenyl) -5-ethoxy-7-hydroxychromen-4-one
MW: 314.289460 g / mol | MF: C17H14O6
149: CID: 44610477
IUPAC: 2- (3,4-dihydroxyphenyl) -7-ethoxy-5-hydroxychromen-4-one
MW: 314.289460 g / mol | MF: C17H14O6
150: CID: 25030204
IUPAC: 7-hydroxy-5-methoxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
151: CID: 25189611
IUPAC: 2- (3-fluoro-4,5-dihydroxyphenyl) -5,7-dihydroxychromen-4-one
MW: 304.226763 g / mol | MF: C15H9FO6
152: CID: 6477683
AIDS154806; CHEBI: 480360; AIDS-154806
IUPAC: 2-[(E) -2- (3,4-dihydroxyphenyl) ethenyl] -5-hydroxychromen-4-one
MW: 296.274180 g / mol | MF: C17H12O5
153: CID: 9860659
CID9860659; 3,5,7-trihydroxy-2- (3-hydroxyphenyl) chromen-4-one
IUPAC: 3,5,7-trihydroxy-2- (3-hydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
154: CID: 632128
CHEBI: 222167; CID632128; LMPK12112763
IUPAC: 2- (3-hydroxy-4-methoxyphenyl) -3,5,7-trimethoxychromen-4-one
MW: 358.342020 g / mol | MF: C19H18O7
155: CID: 5280631
Quercetin 3,3 ', 7-trissulfate; CHEBI: 16557; LMPK12112310
IUPAC: [2-hydroxy-5- (5-hydroxy-4-oxo-3,7-disulfooxychromen-2-yl) phenyl] hydrogen sulfate
MW: 542.425300 g / mol | MF: C15H10O16S3
156: CID: 5280632
Quercetin 3,4 ', 7-trissulfate; CHEBI: 28167; LMPK12112311
IUPAC: [2-hydroxy-4- (5-hydroxy-4-oxo-3,7-disulfooxychromen-2-yl) phenyl] hydrogen sulfate
MW: 542.425300 g / mol | MF: C15H10O16S3
157: CID: 5280682
Ayanin; 3,7,4'-Tri-O-methylquercetin;3,7,4'-trimethylquercetin
IUPAC: 5-hydroxy-2- (3-hydroxy-4-methoxyphenyl) -3,7-dimethoxychromen-4-one
MW: 344.315440 g / mol | MF: C18H16O7
Tested in BioAssays: All: 59, Active: 0
158: CID: 5281677
Pachypodol; CHEBI: 373037; NSC 168805
IUPAC: 5-hydroxy-2- (4-hydroxy-3-methoxyphenyl) -3,7-dimethoxychromen-4-one
MW: 344.315440 g / mol | MF: C18H16O7
159: CID: 5320848
CID5320848; 5-hydroxy-2- (4-hydroxy-3-sulfinatooxy-phenyl) -7-methoxy-4-oxo-3-sulfinatooxy-chromene
IUPAC: [2-hydroxy-5- (5-hydroxy-7-methoxy-4-oxo-3-sulfinatooxychromen-2-yl) phenyl] sulfite
MW: 442.374000 g / mol | MF: C16H10O11S2-2
160: CID: 5400219
Oprea1_158180; Oprea1_711058; MolPort-001-836-336
IUPAC: 7,8-dihydroxy-2-methyl-3-phenoxychromen-4-one
MW: 284.263480 g / mol | MF: C16H12O5
161: CID: 5482937
Quercetin Analogs; AIDS114005; AIDS-114005
IUPAC: [2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-4-oxochromen-3-yl] acetate
MW: 344.272380 g / mol | MF: C17H12O8
162: CID: 5492759
Potassium quercetin phosphate; CID5492759; LS-39610
IUPAC: potassium; 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one; hydrogen phosphate
MW: 437.313301 g / mol | MF: C15H11KO11P-
163: CID: 6105183
Oprea1_065446; Oprea1_827089; CID6105183
IUPAC: 7,8-dihydroxy-3-phenoxychromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
164: CID: 6481478
AIDS337573; MolPort-000-165-393; AIDS-337573
IUPAC: 5,6,7-trihydroxy-3-methoxy-2- (4-methoxyphenyl) chromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
165: CID: 9818879
CHEBI: 303768; CID9818879; 2- (3,4-Dihydroxy-phenyl) -7-hydroxy-3- (2-hydroxy-ethoxy) -chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -7-hydroxy-3- (2-hydroxyethoxy) chromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
166: CID: 10473561
CID10473561; [2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-4-oxo-chromen-3-yl] Propanoate
IUPAC: [2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-4-oxochromen-3-yl] propanoate
MW: 358.298960 g / mol | MF: C18H14O8
167: CID: 10807373
LMPK12111581; CID10807373; 3-hydroxy-2- (4-hydroxy-3,5-dimethoxy-phenyl) -7-methoxy-chromen-4-one
IUPAC: 3-hydroxy-2- (4-hydroxy-3,5-dimethoxyphenyl) -7-methoxychromen-4-one
MW: 344.315440 g / mol | MF: C18H16O7
168: CID: 11834044
LMPK12112862; CID11834044; 5,6,7-trihydroxy-2- (4-hydroxyphenyl) -3-methoxy-chromen-4-one
IUPAC: 5,6,7-trihydroxy-2- (4-hydroxyphenyl) -3-methoxychromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
169: CID: 13942543
CHEBI: 405386; LMPK12112755; 2- (4-Hydroxy-3-methoxy-phenyl) -3,5,7-trimethoxy-chromen-4-one
IUPAC: 2- (4-hydroxy-3-methoxyphenyl) -3,5,7-trimethoxychromen-4-one
MW: 358.342020 g / mol | MF: C19H18O7
170: CID: 14079475
LMPK12111600
IUPAC: 3,7-dihydroxy-8-methoxy-2-phenylchromen-4-one
MW: 284.263480 g / mol | MF: C16H12O5
171: CID: 14162697
CHEBI: 405173; LMPK12112753; 7-Hydroxy-2- (4-hydroxy-3-methoxy-phenyl) -3,5-dimethoxy-chromen-4-one
IUPAC: 7-hydroxy-2- (4-hydroxy-3-methoxyphenyl) -3,5-dimethoxychromen-4-one
MW: 344.315440 g / mol | MF: C18H16O7
172: CID: 18372853
IUPAC: 2- (3,4-dihydroxyphenyl) -3,8-dihydroxy-7-methoxychromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
173: CID: 19890110
IUPAC: 3-hydroxy-2- (2-hydroxy-3,4-dimethoxyphenyl) -5,7-dimethoxychromen-4-one
MW: 374.341420 g / mol | MF: C19H18O8
174: CID: 20159736
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3- (2-hydroxyethoxy) chromen-4-one
MW: 346.288260 g / mol | MF: C17H14O8
175: CID: 20833257
IUPAC: [2-hydroxy-5- (3,5,7-trihydroxy-4-oxochromen-2-yl) phenyl] dihydrogen phosphate
MW: 382.215601 g / mol | MF: C15H11O10P
176: CID: 20981198
IUPAC: potassium 2- (3,4-dihydroxyphenyl) -3,5,7-trihydroxychromen-4-one phosphate
MW: 436.305361 g / mol | MF: C15H10KO11P-2
177: CID: 22138197
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3- (2,2,2-trihydroxyethoxy) chromen-4-one
MW: 378.287060 g / mol | MF: C17H14O10
178: CID: 25183346
IUPAC: [2-hydroxy-4- (3,5,7-trihydroxy-4-oxochromen-2-yl) phenyl] dihydrogen phosphate
MW: 382.215601 g / mol | MF: C15H11O10P
179: CID: 44258703
LMPK12111607
IUPAC: 2- (3,4-dihydroxyphenyl) -3,7-dihydroxy-8-methoxychromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
180: CID: 44258706
LMPK12111610
IUPAC: 3,7,8-trihydroxy-2- (4-hydroxy-3-methoxyphenyl) chromen-4-one
MW: 316.262280 g / mol | MF: C16H12O7
181: CID: 44259678
LMPK12112722
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3-methoxy-6-methylchromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
182: CID: 44259679
LMPK12112723
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3-methoxy-8-methylchromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
183: CID: 44594804
IUPAC: [2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-4-oxochromen-3-yl] dihydrogen phosphate
MW: 382.215601 g / mol | MF: C15H11O10P
184: CID: 5281953
Syringetin; 3 ', 5'-O-Dimethylmyricetin; CHEBI: 18215
IUPAC: 3,5,7-trihydroxy-2- (4-hydroxy-3,5-dimethoxyphenyl) chromen-4-one
MW: 346.288260 g / mol | MF: C17H14O8
185: CID: 5282154
Laricitrin; 3'-O-Methylmyricetin; LMPK12112482
IUPAC: 2- (3,4-dihydroxy-5-methoxyphenyl) -3,5,7-trihydroxychromen-4-one
MW: 332.261680 g / mol | MF: C16H12O8
186: CID: 5315126
Uralenol; CHEBI: 288124; LMPK12112286
IUPAC: 2- [3,4-dihydroxy-5- (3-methylbut-2-enyl) phenyl] -3,5,7-trihydroxychromen-4-one
MW: 370.352720 g / mol | MF: C20H18O7
187: CID: 10343070
Broussonol E; CHEBI: 565773; LMPK12112289
IUPAC: 2- [3,4-dihydroxy-5- (3-methylbut-2-enyl) phenyl] -3,5,7-trihydroxy-6- (3-methylbut-2-enyl) chromen-4-one
MW: 438.469740 g / mol | MF: C25H26O7
188: CID: 10359384
mearnsetin; CHEBI: 583367; LMPK12112506
IUPAC: 2- (3,5-dihydroxy-4-methoxyphenyl) -3,5,7-trihydroxychromen-4-one
MW: 332.261680 g / mol | MF: C16H12O8
189: CID: 10365850
Broussonol D; CHEBI: 565772; LMPK12112290
IUPAC: 2- [3,4-dihydroxy-5- (3-methylbut-2-enyl) phenyl] -3,5,7-trihydroxy-8- (3-methylbut-2-enyl) chromen-4-one
MW: 438.469740 g / mol | MF: C25H26O7
190: CID: 12314325
LMPK12112469
IUPAC: 3,5,7-trihydroxy-6-methyl-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 332.261680 g / mol | MF: C16H12O8
191: CID: 15559735
LMPK12113272
IUPAC: 3,5,7,8-tetrahydroxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 334.234500 g / mol | MF: C15H10O9
192: CID: 21676176
quercetin 3, 7, 4-trisulphate; quercetin 3, 7, 4'-trisulphate; CPD-10893
IUPAC: [2-hydroxy-4- (5-hydroxy-4-oxo-3,7-disulfonatooxychromen-2-yl) phenyl] sulfate
MW: 539.401480 g / mol | MF: C15H7O16S3-3
193: CID: 21676177
Quercetin 3,3 ', 7-trissulfate; QUERCETIN-337-TRISSULFATE
IUPAC: [2-hydroxy-5- (5-hydroxy-4-oxo-3,7-disulfonatooxychromen-2-yl) phenyl] sulfate
MW: 539.401480 g / mol | MF: C15H7O16S3-3
194: CID: 22507435
IUPAC: 3,5,7-trimethoxy-2- (3,4,5-trihydroxyphenyl) chromen-4-one
MW: 360.314840 g / mol | MF: C18H16O8
195: CID: 25202456
Syringetin
IUPAC: 5,7-dihydroxy-2- (4-hydroxy-3,5-dimethoxyphenyl) -4-oxochromen-3-olate
MW: 345.280320 g / mol | MF: C17H13O8-
196: CID: 25203006
Laricitrin; CPD-8605
IUPAC: 2-hydroxy-6-methoxy-4- (3,5,7-trihydroxy-4-oxochromen-2-yl) phenolate
MW: 331.253740 g / mol | MF: C16H11O8-
197: CID: 44259511
LMPK12112509
IUPAC: 3,5,7-trihydroxy-2- (3-hydroxy-4,5-dimethoxyphenyl) chromen-4-one
MW: 346.288260 g / mol | MF: C17H14O8
198: CID: 44259638
LMPK12112666
IUPAC: 2- (3,5-dihydroxy-4-methoxyphenyl) -3,5-dihydroxy-7-methoxychromen-4-one
MW: 346.288260 g / mol | MF: C17H14O8
199: CID: 96506
Nortangeretin; MLS000736839; CHEBI: 493043
IUPAC: 5,6,7,8-tetrahydroxy-2- (4-hydroxyphenyl) chromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
Tested in BioAssays: All: 182, Active: 17
200: CID: 797370
Oprea1_264669; Oprea1_552685; MolPort-001-831-555
IUPAC: 2-phenoxy-1- (2,3,4-trihydroxyphenyl) ethanone
MW: 260.242080 g / mol | MF: C14H12O5
201: CID: 5280666
Chrysoeriol; Chryseriol; 3'-Methoxyapigenin
IUPAC: 5,7-dihydroxy-2- (4-hydroxy-3-methoxyphenyl) chromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
Tested in BioAssays: All: 261, Active: 6
202: CID: 5281612
Diosmetin; 4'-Methylluteolin; Luteolin 4'-methyl ether
IUPAC: 5,7-dihydroxy-2- (3-hydroxy-4-methoxyphenyl) chromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
Tested in BioAssays: All: 24, Active: 2
203: CID: 5281648
Hypolaetin; 8-Hydroxyluteolin; CHEBI: 5837
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7,8-trihydroxychromen-4-one
MW: 302.235700 g / mol | MF: C15H10O7
204: CID: 5281665
Isoscutellarein; 8-Hydroxyapigenin; LMPK12111361
IUPAC: 5,7,8-trihydroxy-2- (4-hydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
205: CID: 5281674
Norwogonin; nor-wogonin; 5,7,8-Trihydroxyflavone
IUPAC: 5,7,8-trihydroxy-2-phenylchromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
Tested in BioAssays: All: 5, Active: 1
206: CID: 5320496
Pilloin; Luteolin 7,4'-dimethyl ether; CHEBI: 583719
IUPAC: 5-hydroxy-2- (3-hydroxy-4-methoxyphenyl) -7-methoxychromen-4-one
MW: 314.289460 g / mol | MF: C17H14O6
207: CID: 5464381
Velutin; Flavonoid; Luteolin 7,3'-dimethyl ether
IUPAC: 5-hydroxy-2- (4-hydroxy-3-methoxyphenyl) -7-methoxychromen-4-one
MW: 314.289460 g / mol | MF: C17H14O6
208: CID: 5487855
sec-Butyl benzoate; 3 ', 4'-Dimethoxyquercetin; LMPK12112411
IUPAC: 2- (3,4-dimethoxyphenyl) -3,5,7-trihydroxychromen-4-one
MW: 330.288860 g / mol | MF: C17H14O7
209: CID: 10357421
CID10357421; 2- (3,4-dihydroxyphenyl) -3,5-dihydroxy-7-methyl-chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -3,5-dihydroxy-7-methylchromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
210: CID: 11474580
CID11474580; 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3- (3-methylbut-2-enoxymethyl) chromen-4-one
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-3- (3-methylbut-2-enoxymethyl) chromen-4-one
MW: 384.379300 g / mol | MF: C21H20O7
211: CID: 13964547
CHEBI: 405387; LMPK12110968; 7-Hydroxy-2- (3-hydroxy-4-methoxy-phenyl) -5-methoxy-chromen-4-one
IUPAC: 7-hydroxy-2- (3-hydroxy-4-methoxyphenyl) -5-methoxychromen-4-one
MW: 314.289460 g / mol | MF: C17H14O6
212: CID: 13964549
Chrysoeriol 5-methyl ether; LMPK12110967
IUPAC: 7-hydroxy-2- (4-hydroxy-3-methoxyphenyl) -5-methoxychromen-4-one
MW: 314.289460 g / mol | MF: C17H14O6
213: CID: 14016780
LMPK12110734
IUPAC: [2- (3,4-dihydroxyphenyl) -5-hydroxy-4-oxochromen-7-yl] hydrogen sulfate
MW: 366.299500 g / mol | MF: C15H10O9S
214: CID: 15293760
LMPK12110728
IUPAC: 2- (3,4-dihydroxyphenyl) -5,7-dihydroxy-6-methylchromen-4-one
MW: 300.262880 g / mol | MF: C16H12O6
215: CID: 21725619
IUPAC: [2-hydroxy-4- (5-hydroxy-4-oxo-7-sulfonatooxychromen-2-yl) phenyl] sulfate
MW: 444.346820 g / mol | MF: C15H8O12S2-2
216: CID: 44258151
LMPK12110735
IUPAC: [5- (5,7-dihydroxy-4-oxochromen-2-yl) -2-hydroxyphenyl] hydrogen sulfate
MW: 366.299500 g / mol | MF: C15H10O9S
217: CID: 44258152
LMPK12110736
IUPAC: [4- (5,7-dihydroxy-4-oxochromen-2-yl) -2-hydroxyphenyl] hydrogen sulfate
MW: 366.299500 g / mol | MF: C15H10O9S
218: CID: 44608109
IUPAC: 7-butoxy-2- (3,4-dihydroxyphenyl) -5-hydroxychromen-4-one
MW: 342.342620 g / mol | MF: C19H18O6
219: CID: 44610310
IUPAC: 2- (3,4-dihydroxyphenyl) -7-hydroxy-5-octoxychromen-4-one
MW: 398.448940 g / mol | MF: C23H26O6
220: CID: 44610311
IUPAC: 2- (3,4-dihydroxyphenyl) -7-hydroxy-5-propoxychromen-4-one
MW: 328.316040 g / mol | MF: C18H16O6
221: CID: 44610312
IUPAC: 5-decoxy-2- (3,4-dihydroxyphenyl) -7-hydroxychromen-4-one
MW: 426.502100 g / mol | MF: C25H30O6
222: CID: 44610313
IUPAC: 2- (3,4-dihydroxyphenyl) -5-hexoxy-7-hydroxychromen-4-one
MW: 370.395780 g / mol | MF: C21H22O6
223: CID: 44610474
IUPAC: 5-butoxy-2- (3,4-dihydroxyphenyl) -7-hydroxychromen-4-one
MW: 342.342620 g / mol | MF: C19H18O6
224: CID: 1880
7,8-dihydroxyflavone; FLAVONE; 7,8-Dihydroxy-flavone
IUPAC: 7,8-dihydroxy-2-phenylchromen-4-one
MW: 254.237500 g / mol | MF: C15H10O4
Tested in BioAssays: All: 92, Active: 8
225: CID: 676309
TNP00055; CHEBI: 490243; CID676309
IUPAC: 7,8-dihydroxy-2- (2-hydroxyphenyl) chromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
Tested in BioAssays: All: 80, Active: 18
226: CID: 688853
7,8,4-trihydroxyflavone; CHEBI: 246131; ZINC00057915
IUPAC: 7,8-dihydroxy-2- (4-hydroxyphenyl) chromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
227: CID: 9814421
CID9814421; 2- (2,4-dihydroxyphenyl) -7,8-dihydroxy-chromen-4-one
IUPAC: 2- (2,4-dihydroxyphenyl) -7,8-dihydroxychromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
228: CID: 18778789
IUPAC: (2E) -2-[(3,4-dihydroxyphenyl) methylidene] -7-hydroxychromen-4-one
MW: 284.263480 g / mol | MF: C16H12O5
229: CID: 17840570
IUPAC: (3,5,6-trihydroxy-2-phenylchromen-4-ylidene) oxidanium
MW: 271.244840 g / mol | MF: C15H11O5 +
230: CID: 17840571
IUPAC: 3,5,6-trihydroxy-2-phenylchromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
231: CID: 23064865
IUPAC: 2- (2,3,4,6-tetrahydroxyphenyl) chromen-4-one
MW: 286.236300 g / mol | MF: C15H10O6
232: CID: 5393165
ZINC00057845; CID5393165
IUPAC: 3,7-dihydroxy-2- (3-hydroxyphenyl) chromen-4-one
MW: 270.236900 g / mol | MF: C15H10O5
233: CID: 20977459
IUPAC: [3,5,7-trihydroxy-2- (3-hydroxyphenyl) chromen-4-ylidene] oxidanium chloride
MW: 322.697240 g / mol | MF: C15H11ClO6
当業者であれば、後述の実施例の実験データを参照すれば、これらの類似度(tanimoto係数)95%以上の233種類の化合物が、当然に間葉系幹細胞の肝細胞への分化を誘導する性質を有することを理解できる。 Those skilled in the art will refer to the experimental data of Examples described later, and 233 kinds of compounds having a similarity (tanimoto coefficient) of 95% or more naturally induce differentiation of mesenchymal stem cells into hepatocytes. Can be understood.
(iii)イオノマイシン
本明細書において、「イオノマイシン」(Ionomycin)とは、PubChemから引用すると、以下の特性を有する化合物であり、化学式(3)で表される。
Compound ID 44134784
IUPAC: calcium 19,21-dihydroxy-22-[5-[5-(1-hydroxyethyl)-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
Molecular Weight 747.0671 [g/mol]
Molecular Formula C41H70CaO9
H-Bond Donor 3
H-Bond Acceptor 9
(Iii) Ionomycin In this specification, “ionomycin” (Ionomycin) is a compound having the following characteristics and is represented by the chemical formula (3), when quoted from PubChem.
Compound ID 44134784
IUPAC: calcium 19,21-dihydroxy-22- [5- [5- (1-hydroxyethyl) -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14 , 18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
Molecular Weight 747.0671 [g / mol]
Molecular Formula C41H70CaO9
H-Bond Donor 3
H-Bond Acceptor 9
イオノマイシンの類縁体としては、特に限定するものではないが、例えばPubChemのCompound Structure Search において類似度(tanimoto係数)95%以上で検索すると、以下の20種類の化合物が類縁体に含まれる。なお、類縁体に含めるtanimoto係数の下限値は、特に限定されず、例えば、90%以上でもよく、91%以上でもよく、92%以上でもよく、93%以上でもよく、94%以上でもよく、95%以上でもよく、96%以上でもよく、97%以上でもよく、98%以上でもよく、99%以上でもよい。類似度(tanimoto係数)が大きければ大きいほどリード化合物に構造・生理活性などが近似した類縁体である可能性が高くなる。なお、tanimoto係数の計算式は既述のとおりであり、ケモインフォマティクスの分野では最も頻繁に使われる権威ある化合物同士の類似係数である。 The analog of ionomycin is not particularly limited. For example, when searching with Compound Structure Search of PubChem with a similarity (tanimoto coefficient) of 95% or more, the following 20 types of compounds are included in the analog. The lower limit of the tanimoto coefficient included in the analog is not particularly limited, and may be, for example, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, It may be 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more. The greater the degree of similarity (tanimoto coefficient), the higher the possibility of being an analog having a structure / physiological activity that approximates the lead compound. The formula for calculating the tanimoto coefficient is as described above, and is a similarity coefficient between the most prestigious compounds used most frequently in the field of chemoinformatics.
イオノマイシンの類似度(tanimoto係数)95%以上の類縁体一覧
1: CID: 6446270
Ionomycin, calcium salt; MolPort-003-983-599; CID6446270
IUPAC: calcium (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-19,21-dihydroxy-22-[(2S,5S)-5-[(2R,5S)-5-[(1R)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
MW: 747.067100 g/mol | MF: C41H70CaO9
2: CID: 24839624
LS-84163
IUPAC: calcium; (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-11,19,21-trihydroxy-22-[(2S,5S)-5-[(2R,5S)-5-[(1R)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 749.082980 g/mol | MF: C41H72CaO9
3: CID: 42602091
IUPAC: calcium (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-11,19,21-trihydroxy-22-[(2R,5R)-5-[(2S,5R)-5-[(1S)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 749.082980 g/mol | MF: C41H72CaO9+2
4: CID: 44120021
BII0123
IUPAC: calcium (4S,6R,8R,10Z,12S,14S,16E,18S,19S,20R,21S)-19,21-dihydroxy-22-[(2R,5S)-5-[(2S,5S)-5-[(1R)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
MW: 747.067100 g/mol | MF: C41H70CaO9
5: CID: 44134784
ionomycin; 56092-82-1
IUPAC: calcium 19,21-dihydroxy-22-[5-[5-(1-hydroxyethyl)-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
MW: 747.067100 g/mol | MF: C41H70CaO9
Ionophores more
6: CID: 3733
ionomycin; CID3733; 56092-81-0
IUPAC: 11,19,21-trihydroxy-22-[5-[5-(1-hydroxyethyl)-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
Ionophores more
7: CID: 3611369
CID3611369; CID 3611369
IUPAC: 19,21-dihydroxy-22-[5-[5-(1-hydroxyethyl)-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
MW: 706.989100 g/mol | MF: C41H70O9-2
8: CID: 6434517
ionomycin; CID6434517; LS-84162
IUPAC: (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-11,19,21-trihydroxy-22-[(5S)-5-[(5S)-5-[(1R)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
Ionophores more
9: CID: 6711156
ionomycin; MolMap_000033; CID6711156
IUPAC: (4R,6S,8S,12R,14R,18R,19R,20S,21S)-11,19,21-trihydroxy-22-[(2R,5R)-5-[(2R,5S)-5-[(1R)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
Ionophores more
10: CID: 6912226
ionomycin; CHEBI:566812; HSCI1_000207
IUPAC: (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-11,19,21-trihydroxy-22-[(2S,5S)-5-[(2R,5S)-5-[(1R)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
Ionophores more
11: CID: 9831149
CID9831149; CID 9831149
IUPAC: (10Z,16E)-11,19-dihydroxy-20-[5-[5-(1-hydroxyethyl)-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-2,4,6,8,12,14,18-heptamethyl-9-oxoicosa-10,16-dienoic acid
MW: 664.952420 g/mol | MF: C39H68O8
12: CID: 10372625
ionomycin; CID10372625
IUPAC: (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-11,19,21-trihydroxy-22-[(2R,5R)-5-[(2S,5R)-5-[(1S)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
Ionophores more
13: CID: 12967103
NCGC00162460-01
IUPAC: (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-11,19,21-trihydroxy-22-[(2S,5S)-5-[(5S)-5-[(1R)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
Tested in BioAssays: All: 34, Active: 1
14: CID: 16219538
I9657_SIGMA; Ionomycin from Streptomyces conglobatus
IUPAC: (4S,6R,8R,10Z,12S,14S,16E,18S,19S,20R,21S)-11,19,21-trihydroxy-22-[(5S)-5-[(5S)-5-[(1S)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
15: CID: 16759612
NCGC00162463-01
IUPAC: (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-19,21-dihydroxy-22-[(2S,5S)-5-[(2R,5S)-5-[(1R)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
MW: 706.989100 g/mol | MF: C41H70O9-2
Tested in BioAssays: All: 34, Active: 0
16: CID: 24742080
nchembio.79-comp37; 4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-11,19,21-Trihydroxy-4,6,8,12,14,18,20-heptamethyl-22-[(2S,2’R,5S,5’S)-octahydro-5’-[(1R)-1-hydroxyethyl]-2,5’-dimethyl[2,2’-bifuran]-5-yl]-9-oxo-10,16-docosadienoic acid calcium salt
IUPAC: (4S,6R,8R,10Z,12S,14S,16E,18S,19S,20R,21S)-19,21-dihydroxy-22-[(5S)-5-[(5S)-5-[(1S)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
MW: 706.989100 g/mol | MF: C41H70O9-2
17: CID: 25134244
ionomycin; nchembio.146-comp9
IUPAC: (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-11,19,21-trihydroxy-22-[(5S)-5-[(5S)-5-(1-hydroxyethyl)-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
Ionophores more
18: CID: 44120022
IUPAC: (4S,6R,8R,10Z,12S,14S,16E,18S,19S,20R,21S)-11,19,21-trihydroxy-22-[(2R,5S)-5-[(2S,5S)-5-[(1R)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
19: CID: 44120023
BII0421
IUPAC: (4R,6S,8S,10Z,12R,14R,16E,18S,19S,20R,21S)-11,19,21-trihydroxy-22-[(2S,5S)-5-[(2S,5R)-5-[(1S)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
20: CID: 44560066
CHEBI:546782; (3R,5S,7S,9Z,11R,13R,15E,17R,18R,19S,20S)-1-carboxy-18,20-dihydroxy-21-((2S,5S)-5-((2R,5S)-5-((S)-1-hydroxyethyl)-5-methyl-tetrahydrofuran-2-yl)-5-methyl-tetrahydrofuran-2-yl)-3,5,7,11,13,17,19-heptamethyl-8-oxohenicosa-9,15-dien-10-olate
IUPAC: (4R,6S,8S,10Z,12R,14R,16E,18R,19R,20S,21S)-11,19,21-trihydroxy-22-[(2S,5S)-5-[(2R,5S)-5-[(1S)-1-hydroxyethyl]-5-methyloxolan-2-yl]-5-methyloxolan-2-yl]-4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g/mol | MF: C41H72O9
List of analogs with ionomycin similarity (tanimoto coefficient) of 95% or more
1: CID: 6446270
Ionomycin, calcium salt; MolPort-003-983-599; CID6446270
IUPAC: calcium (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -19,21-dihydroxy-22-[(2S, 5S) -5-[(2R, 5S) -5-[(1R) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-11-oxido -9-oxodocosa-10,16-dienoate
MW: 747.067100 g / mol | MF: C41H70CaO9
2: CID: 24839624
LS-84163
IUPAC: calcium; (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -11,19,21-trihydroxy-22-[(2S, 5S) -5-[(2R , 5S) -5-[(1R) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl- 9-oxodocosa-10,16-dienoic acid
MW: 749.082980 g / mol | MF: C41H72CaO9
3: CID: 42602091
IUPAC: calcium (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -11,19,21-trihydroxy-22-[(2R, 5R) -5-[(2S, 5R) -5-[(1S) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9 -oxodocosa-10,16-dienoic acid
MW: 749.082980 g / mol | MF: C41H72CaO9 + 2
4: CID: 44120021
BII0123
IUPAC: calcium (4S, 6R, 8R, 10Z, 12S, 14S, 16E, 18S, 19S, 20R, 21S) -19,21-dihydroxy-22-[(2R, 5S) -5-[(2S, 5S) -5-[(1R) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-11-oxido -9-oxodocosa-10,16-dienoate
MW: 747.067100 g / mol | MF: C41H70CaO9
5: CID: 44134784
ionomycin; 56092-82-1
IUPAC: calcium 19,21-dihydroxy-22- [5- [5- (1-hydroxyethyl) -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14 , 18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
MW: 747.067100 g / mol | MF: C41H70CaO9
Ionophores more
6: CID: 3733
ionomycin; CID3733; 56092-81-0
IUPAC: 11,19,21-trihydroxy-22- [5- [5- (1-hydroxyethyl) -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12, 14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
Ionophores more
7: CID: 3611369
CID3611369; CID3611369
IUPAC: 19,21-dihydroxy-22- [5- [5- (1-hydroxyethyl) -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14, 18,20-heptamethyl-11-oxido-9-oxodocosa-10,16-dienoate
MW: 706.989100 g / mol | MF: C41H70O9-2
8: CID: 6434517
ionomycin; CID6434517; LS-84162
IUPAC: (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -11,19,21-trihydroxy-22-[(5S) -5-[(5S) -5- [(1R) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10, 16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
Ionophores more
9: CID: 6711156
ionomycin; MolMap_000033; CID6711156
IUPAC: (4R, 6S, 8S, 12R, 14R, 18R, 19R, 20S, 21S) -11,19,21-trihydroxy-22-[(2R, 5R) -5-[(2R, 5S) -5- [(1R) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10, 16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
Ionophores more
10: CID: 6912226
ionomycin; CHEBI: 566812; HSCI1_000207
IUPAC: (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -11,19,21-trihydroxy-22-[(2S, 5S) -5-[(2R, 5S ) -5-[(1R) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9- oxodocosa-10,16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
Ionophores more
11: CID: 9831149
CID9831149; CID 9831149
IUPAC: (10Z, 16E) -11,19-dihydroxy-20- [5- [5- (1-hydroxyethyl) -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -2,4, 6,8,12,14,18-heptamethyl-9-oxoicosa-10,16-dienoic acid
MW: 664.952420 g / mol | MF: C39H68O8
12: CID: 10372625
ionomycin; CID10372625
IUPAC: (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -11,19,21-trihydroxy-22-[(2R, 5R) -5-[(2S, 5R ) -5-[(1S) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9- oxodocosa-10,16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
Ionophores more
13: CID: 12967103
NCGC00162460-01
IUPAC: (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -11,19,21-trihydroxy-22-[(2S, 5S) -5-[(5S)- 5-[(1R) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9-oxodocosa- 10,16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
Tested in BioAssays: All: 34, Active: 1
14: CID: 16219538
I9657_SIGMA; Ionomycin from Streptomyces conglobatus
IUPAC: (4S, 6R, 8R, 10Z, 12S, 14S, 16E, 18S, 19S, 20R, 21S) -11,19,21-trihydroxy-22-[(5S) -5-[(5S) -5- [(1S) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10, 16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
15: CID: 16759612
NCGC00162463-01
IUPAC: (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -19,21-dihydroxy-22-[(2S, 5S) -5-[(2R, 5S)- 5-[(1R) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-11-oxido- 9-oxodocosa-10,16-dienoate
MW: 706.989100 g / mol | MF: C41H70O9-2
Tested in BioAssays: All: 34, Active: 0
16: CID: 24742080
nchembio.79-comp37; 4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -11,19,21-Trihydroxy-4,6,8,12,14,18,20 -heptamethyl-22-[(2S, 2'R, 5S, 5'S) -octahydro-5 '-[(1R) -1-hydroxyethyl] -2,5'-dimethyl [2,2'-bifuran] -5- yl] -9-oxo-10,16-docosadienoic acid calcium salt
IUPAC: (4S, 6R, 8R, 10Z, 12S, 14S, 16E, 18S, 19S, 20R, 21S) -19,21-dihydroxy-22-[(5S) -5-[(5S) -5-[( 1S) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-11-oxido-9-oxodocosa- 10,16-dienoate
MW: 706.989100 g / mol | MF: C41H70O9-2
17: CID: 25134244
ionomycin; nchembio.146-comp9
IUPAC: (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -11,19,21-trihydroxy-22-[(5S) -5-[(5S) -5- (1-hydroxyethyl) -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9-oxodocosa-10,16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
Ionophores more
18: CID: 44120022
IUPAC: (4S, 6R, 8R, 10Z, 12S, 14S, 16E, 18S, 19S, 20R, 21S) -11,19,21-trihydroxy-22-[(2R, 5S) -5-[(2S, 5S ) -5-[(1R) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9- oxodocosa-10,16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
19: CID: 44120023
BII0421
IUPAC: (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18S, 19S, 20R, 21S) -11,19,21-trihydroxy-22-[(2S, 5S) -5-[(2S, 5R ) -5-[(1S) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9- oxodocosa-10,16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
20: CID: 44560066
CHEBI: 546782; (3R, 5S, 7S, 9Z, 11R, 13R, 15E, 17R, 18R, 19S, 20S) -1-carboxy-18,20-dihydroxy-21-((2S, 5S) -5- ( (2R, 5S) -5-((S) -1-hydroxyethyl) -5-methyl-tetrahydrofuran-2-yl) -5-methyl-tetrahydrofuran-2-yl) -3,5,7,11,13, 17,19-heptamethyl-8-oxohenicosa-9,15-dien-10-olate
IUPAC: (4R, 6S, 8S, 10Z, 12R, 14R, 16E, 18R, 19R, 20S, 21S) -11,19,21-trihydroxy-22-[(2S, 5S) -5-[(2R, 5S ) -5-[(1S) -1-hydroxyethyl] -5-methyloxolan-2-yl] -5-methyloxolan-2-yl] -4,6,8,12,14,18,20-heptamethyl-9- oxodocosa-10,16-dienoic acid
MW: 709.004980 g / mol | MF: C41H72O9
当業者であれば、後述の実施例の実験データを参照すれば、これらの類似度(tanimoto係数)95%以上の20種類の化合物が、当然に間葉系幹細胞の肝細胞への分化を誘導する性質を有することを理解できる。 Those skilled in the art can refer to the experimental data of the examples described later, and these 20 compounds having a similarity (tanimoto coefficient) of 95% or more naturally induce differentiation of mesenchymal stem cells into hepatocytes. Can be understood.
(iv)PKF115−584
本明細書において、「PKF115−584」とは、非特許文献6(Maina Lepourcelet et al., “Small-molecule antagonists of the oncogenic Tcf/β-catenin protein complex”, CANCER CELL, JANUARY 2004, VOL. 5, 91-102)から引用すると、以下の特性を有する化合物であり、化学式(4)で表される。
In this specification, “PKF115-584” refers to Non-Patent Document 6 (Maina Lepourcelet et al., “Small-molecule antagonists of the oncogenic Tcf / β-catenin protein complex”, CANCER CELL, JANUARY 2004, VOL. 5). , 91-102), it is a compound having the following characteristics and is represented by the chemical formula (4).
PKF115−584の類縁体としては、特に限定するものではないが、例えば類似度(tanimoto係数)95%以上の化合物が類縁体に含まれる。なお、類縁体に含めるtanimoto係数の下限値は、特に限定されず、例えば、90%以上でもよく、91%以上でもよく、92%以上でもよく、93%以上でもよく、94%以上でもよく、95%以上でもよく、96%以上でもよく、97%以上でもよく、98%以上でもよく、99%以上でもよい。類似度(tanimoto係数)が大きければ大きいほどリード化合物に構造・生理活性などが近似した類縁体である可能性が高くなる。なお、tanimoto係数の計算式は既述のとおりであり、ケモインフォマティクスの分野では最も頻繁に使われる権威ある化合物同士の類似係数である。 The analog of PKF115-584 is not particularly limited, but, for example, a compound having a similarity (tanimoto coefficient) of 95% or more is included in the analog. The lower limit of the tanimoto coefficient included in the analog is not particularly limited, and may be, for example, 90% or more, 91% or more, 92% or more, 93% or more, 94% or more, It may be 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more. The greater the degree of similarity (tanimoto coefficient), the higher the possibility of being an analog having a structure / physiological activity that approximates the lead compound. The formula for calculating the tanimoto coefficient is as described above, and is a similarity coefficient between the most prestigious compounds used most frequently in the field of chemoinformatics.
当業者であれば、後述の実施例の実験データを参照すれば、これらの類似度(tanimoto係数)95%以上の化合物が、当然に間葉系幹細胞の肝細胞への分化を誘導する性質を有することを理解できる。 If a person skilled in the art refers to the experimental data in the examples described later, these compounds having a similarity (tanimoto coefficient) of 95% or more naturally induce the differentiation of mesenchymal stem cells into hepatocytes. I understand that I have it.
なお、本実施形態において、分化誘導剤の候補物質である有機低分子量化合物が、間葉系幹細胞を肝細胞に分化誘導する性質を有するかどうか判断するには、間葉系幹細胞におけるアルブミン、C/EBPα、CYPA1/A2およびAFPからなる群から選ばれる1種以上の蛋白質の発現を誘導するかどうかが重要な指標となる。なぜなら、一般的には、肝細胞ではこれらのアルブミン、C/EBPα、CYPA1/A2およびAFPからなる群から選ばれる1種以上の蛋白質が多量に発現しているのに対して、間葉系幹細胞ではこれらのアルブミン、C/EBPα、CYPA1/A2およびAFPからなる群から選ばれる1種以上の蛋白質が少量しか発現していないからである。 In this embodiment, in order to determine whether an organic low molecular weight compound that is a candidate substance for a differentiation inducer has a property of inducing differentiation of mesenchymal stem cells into hepatocytes, albumin, C in mesenchymal stem cells, Whether to induce the expression of one or more proteins selected from the group consisting of / EBPα, CYPA1 / A2 and AFP is an important indicator. Because, generally, hepatocytes express a large amount of one or more proteins selected from the group consisting of albumin, C / EBPα, CYPA1 / A2, and AFP, whereas mesenchymal stem cells This is because only a small amount of one or more proteins selected from the group consisting of albumin, C / EBPα, CYPA1 / A2 and AFP is expressed.
この場合、どの程度多量にこれらのアルブミン、C/EBPα、CYPA1/A2およびAFPからなる群から選ばれる1種以上の蛋白質が発現していれば間葉系幹細胞を肝細胞に分化誘導すると判断すべきかが問題になるが、例えば、これらの発現量が候補物質による処理後の間葉系幹細胞で所定の閾値を超えていれば、候補物質が間葉系幹細胞を肝細胞に分化誘導すると判定することができる。一方、これらの発現量が所定の閾値を下回れば、候補物質が間葉系幹細胞を肝細胞に分化誘導する性質を有さないと判定することができる。この閾値は、例えば処理前の間葉系幹細胞の発現量のアルブミン、C/EBPα、CYPA1/A2およびAFPのそれぞれの平均値の1.5倍以上に設定してもよく、2倍以上に設定してもよく、5倍以上に設定してもよく、10倍以上に設定してもよい。また、この閾値は、例えば処理前の間葉系幹細胞の発現量のアルブミン、C/EBPα、CYPA1/A2およびAFPのそれぞれの平均値よりも標準偏差の2倍以上大きい場合に設定してもよく、標準偏差の5倍以上大きい場合に設定してもよく、標準偏差の10倍以上大きい場合に設定してもよい。 In this case, it should be judged that how much of these proteins express one or more proteins selected from the group consisting of albumin, C / EBPα, CYPA1 / A2 and AFP to induce differentiation of mesenchymal stem cells into hepatocytes. For example, if the expression level of the mesenchymal stem cells after the treatment with the candidate substance exceeds a predetermined threshold, it is determined that the candidate substance induces differentiation of the mesenchymal stem cells into hepatocytes. be able to. On the other hand, if these expression levels are below a predetermined threshold, it can be determined that the candidate substance does not have the property of inducing differentiation of mesenchymal stem cells into hepatocytes. This threshold value may be set to 1.5 times or more of the average value of albumin, C / EBPα, CYPA1 / A2 and AFP in the expression level of mesenchymal stem cells before treatment, for example, or more than 2 times. It may be set to 5 times or more, or may be set to 10 times or more. In addition, this threshold value may be set when, for example, the expression level of mesenchymal stem cells before treatment is more than twice the standard deviation of the average value of albumin, C / EBPα, CYPA1 / A2, and AFP. It may be set when it is 5 times or more larger than the standard deviation, or may be set when it is larger than 10 times the standard deviation.
あるいは、候補物質で処理された間葉系幹細胞におけるアルブミン、C/EBPα、CYPA1/A2およびAFPのいずれかの発現量が、例えば処理前の間葉系幹細胞の発現量に比べて有意差が認められるほど大きいかどうかで判定してもよい。有意差があるかどうかの判定としては、例えば母集団が正規分布に従うと仮定できる場合にはパラメトリック検定であるスチューデントのt検定(Student’s t−test)において有意差があれば好ましい。すなわち、スチューデントのt検定において片側検定でp<0.05となればよく、より好ましくは片側検定でp<0.03となればよく、最も好ましくは片側検定でp<0.01となればよい。なお、スチューデントのt検定は特に片側検定に限定するわけではなく、両側検定で行っても良い。さらに、母集団が正規分布に従うと仮定できない場合には、ノンパラメトリック検定として、マン・ホイットニーのU検定などを行って有意差の有無を検定してもよい。 Alternatively, the expression level of any of albumin, C / EBPα, CYPA1 / A2 and AFP in the mesenchymal stem cells treated with the candidate substance is significantly different from the expression level of the mesenchymal stem cells before the treatment, for example. You may judge by whether it is so large as possible. For the determination of whether there is a significant difference, for example, when it can be assumed that the population follows a normal distribution, it is preferable that there is a significant difference in Student's t-test, which is a parametric test. That is, in the Student's t-test, one-sided test should be p <0.05, more preferably one-sided test should be p <0.03, and most preferably one-sided test should be p <0.01. Good. The student t-test is not limited to a one-sided test, but may be a two-sided test. Further, when it cannot be assumed that the population follows a normal distribution, the presence or absence of a significant difference may be tested by performing a Mann-Whitney U test as a nonparametric test.
また、本実施形態において、分化誘導剤の候補物質である有機低分子量化合物が、間葉系幹細胞を肝細胞に分化誘導する性質を有するかどうか判断するには、間葉系幹細胞におけるグリコーゲン生産能または尿素合成能を増強するかどうかが別の重要な指標となる。なぜなら、一般的には、肝細胞ではこれらのグリコーゲン生産能または尿素合成能が増強yされているのに対して、間葉系幹細胞ではこれらのグリコーゲン生産能または尿素合成能が増強されていないからである。この場合、どの程度これらのグリコーゲン生産能または尿素合成能が増強されていれば間葉系幹細胞を肝細胞に分化誘導すると判断すべきかが問題になるが、例えば、上記のアルブミン、C/EBPα、CYPA1/A2およびAFPのいずれかの発現量による判断の場合と同様の方法を用いて閾値または有意差によって判断することができる。 In this embodiment, in order to determine whether the organic low molecular weight compound that is a candidate substance for a differentiation inducer has the property of inducing differentiation of mesenchymal stem cells into hepatocytes, the ability to produce glycogen in mesenchymal stem cells Alternatively, whether or not the ability to synthesize urea is enhanced is another important indicator. This is because, in general, hepatocytes have enhanced ability to produce glycogen or urea, whereas mesenchymal stem cells have not enhanced ability to produce glycogen or urea. It is. In this case, the extent to which these glycogen producing ability or urea synthesizing ability is enhanced determines whether to induce differentiation of mesenchymal stem cells into hepatocytes. For example, albumin, C / EBPα, It can be judged by a threshold value or a significant difference using the same method as in the case of judgment by the expression level of either CYPA1 / A2 or AFP.
<間葉系幹細胞から肝細胞を生産する方法>
本実施形態に係るから肝細胞を生産する方法は、間葉系幹細胞を上記の分化誘導剤で処理する工程を含む、生産方法である。この方法によれば、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いるので、蛋白製剤や核酸製剤に比べ安定性・安全性などの面で優れており、間葉系幹細胞から肝細胞への分化誘導を効率よく安全に行うことができる。
<Method for producing hepatocytes from mesenchymal stem cells>
The method for producing hepatocytes according to this embodiment is a production method including a step of treating mesenchymal stem cells with the above differentiation inducer. According to this method, since an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway is used, it is superior in terms of stability and safety as compared with protein preparations and nucleic acid preparations. From mesenchymal stem cells to hepatocytes Differentiation can be efficiently and safely performed.
この場合、どのような条件で処理すればよいかが問題になるが、処理時間については、後述する実施例で実証されているように、間葉系幹細胞を分化誘導剤で8日以上処理する工程を含むことが好ましい。なぜなら、間葉系幹細胞から肝細胞への分化は生物的なプロセスであるため、細胞内での各種分子生物学的変化が進行するのにその程度の期間がかかってしまうからである。このとき、本実施形態にかかる分化誘導剤は有機低分子量化合物であるため安定性に優れているので、8日以上という長期にわたる処理において分解されてしまう可能性は低い。しかしながら、間葉系幹細胞の生存・増殖・変化に必要な栄養素を供給するためには培地を適宜交換することが好ましく、その際には新しく交換される培地にも交換前の培地と同程度の有機低分子量化合物を添加しておくことが好ましい。また、処理温度についても、本実施形態にかかる分化誘導剤は有機低分子量化合物であるため安定性に優れているので、温度の高低によって分解されてしまう可能性は低い。しかしながら、間葉系幹細胞の生存・増殖・変化に必要な環境を維持するためには培地を哺乳動物細胞の生存に適した温度にすることが好ましく、具体的には20〜45℃の範囲内にしておくことがよく、特に30〜40℃の間に維持することが好ましく、36〜38℃前後に設定することが最も好ましい。 In this case, it is a question of what conditions should be treated, but the processing time is a step of treating mesenchymal stem cells with a differentiation-inducing agent for 8 days or more as demonstrated in the examples described later. It is preferable to contain. This is because differentiation from mesenchymal stem cells to hepatocytes is a biological process, and it takes a certain period of time for various molecular biological changes to proceed in the cells. At this time, since the differentiation-inducing agent according to the present embodiment is an organic low molecular weight compound, it has excellent stability, and therefore, it is unlikely to be decomposed in a long-term treatment of 8 days or longer. However, in order to supply nutrients necessary for the survival, proliferation, and change of mesenchymal stem cells, it is preferable to change the medium as appropriate. In this case, the medium to be replaced is the same as the medium before replacement. It is preferable to add an organic low molecular weight compound. In addition, regarding the processing temperature, the differentiation inducer according to the present embodiment is an organic low molecular weight compound and thus has excellent stability, so that it is unlikely to be decomposed due to the temperature. However, in order to maintain the environment necessary for the survival, proliferation, and change of mesenchymal stem cells, it is preferable to set the medium to a temperature suitable for the survival of mammalian cells, specifically within the range of 20 to 45 ° C. In particular, it is preferably maintained between 30 and 40 ° C, and most preferably set at around 36 to 38 ° C.
この場合、間葉系幹細胞の培養方法は特に限定されないが、例えば温度感受性細胞シートなどの上で哺乳動物細胞の生存に適した培地中で有機低分子量化合物に接触されることが好ましい。例えば、ダルベッコ変法イーグル培地(Dulbecco’s modified Eagle modeium;DMEM)やヒト間葉系幹細胞専用培地(Mesenchymal Stem Cell Basal Medium;MSCBM)などの培地を好適に用いることができる。 In this case, the method for culturing mesenchymal stem cells is not particularly limited. For example, it is preferable to contact the organic low molecular weight compound in a medium suitable for the survival of mammalian cells on a temperature sensitive cell sheet or the like. For example, a medium such as Dulbecco's modified Eagle medium (DMEM) or a medium dedicated to human mesenchymal stem cells (Mesenchymal Stem Cell Basal Medium; MSCBM) can be preferably used.
その際、温度感受性細胞シートとしては、温度応答性ポリマー(PIPAAmなど)やメチルセルロースを表面に重合させた培養皿などを用いることが好ましい。なぜなら、温度を低下させるのみで細胞に損傷を与えることなく、かつ細胞間の接着を保ったまま回収することが可能だからである。 In that case, as the temperature sensitive cell sheet, it is preferable to use a temperature responsive polymer (such as PIPAAm) or a culture dish in which methylcellulose is polymerized on the surface. This is because it is possible to recover the cells without damaging the cells only by lowering the temperature and maintaining the adhesion between the cells.
<再生医療上の用途>
このようにして分化誘導された肝細胞は、肝細胞移植などの移植医療、薬の薬効や副作用を評価する創薬などの用途に好適に用いることができる。また、この肝細胞は、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いて間葉系幹細胞から分化誘導されるので、蛋白製剤や核酸製剤を用いて分化誘導される場合に比べ製造時の安定性・安全性などの面で優れている。
<Applications for regenerative medicine>
The hepatocytes induced to differentiate in this manner can be suitably used for transplantation medicine such as hepatocyte transplantation, drug discovery for evaluating drug efficacy and side effects, and the like. In addition, since these hepatocytes are induced to differentiate from mesenchymal stem cells using an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway, they are produced in comparison with the case where differentiation is induced using a protein preparation or a nucleic acid preparation. Excellent in terms of time stability and safety.
また、このようにして分化誘導された肝細胞は、温度感受性培養皿やポリ−乳酸(PLA)、ポリエチレングリコール酸(PGA)などの生分解性合成ポリマーを使用した合成ポリマースキャフォールドなどの基材を用いて所望の形態に成長させて再生医療用の肝組織または肝臓としても用いることができる。このようにして立体構造を形成された再生医療用の肝組織または肝臓は、肝細胞移植などの移植医療、薬の薬効や副作用を評価する創薬などの用途に好適に用いることができる。また、この肝組織または肝臓は、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いて間葉系幹細胞から分化誘導されるので、蛋白製剤や核酸製剤を用いて分化誘導される場合に比べ製造時の安定性・安全性などの面で優れている。 In addition, hepatocytes induced to differentiate in this way are temperature sensitive culture dishes, base materials such as synthetic polymer scaffolds using biodegradable synthetic polymers such as poly-lactic acid (PLA) and polyethylene glycolic acid (PGA). And can be used as a liver tissue or liver for regenerative medicine. The liver tissue or liver for regenerative medicine in which a three-dimensional structure is formed in this way can be suitably used for uses such as transplantation medicine such as hepatocyte transplantation, drug discovery for evaluating drug efficacy and side effects. In addition, since this liver tissue or liver is induced to differentiate from mesenchymal stem cells using an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway, when differentiation is induced using a protein preparation or a nucleic acid preparation Compared to manufacturing stability and safety.
以上、図面を参照して本発明の実施形態について述べたが、これらは本発明の例示であり、上記以外の様々な構成を採用することもできる。 As mentioned above, although embodiment of this invention was described with reference to drawings, these are the illustrations of this invention, Various structures other than the above are also employable.
以下、本発明を実施例によりさらに説明するが、本発明はこれらに限定されるものではない。 EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not limited to these.
本実施例では、Wnt/β−catenin経路抑制性低分子化合物のヒト間葉系幹細胞へ及ぼす効果について、2種類の細胞(骨髄由来細胞(UE7T−13細胞)、臍帯血由来細胞(UCBTERT−21細胞))をヘキサクロロフェン、ケルセチン、イオノマイシン、PKF−115−584の4種類の低分子化合物で処理した場合について(1)増殖能(毒性)の検討、(2)Wnt/β−catenin経路抑制能の検討、(3)肝細胞分化能の検討を検討項目とした。 In this example, two types of cells (bone marrow-derived cells (UE7T-13 cells), umbilical cord blood-derived cells (UCBTERT-21) regarding the effects of Wnt / β-catenin pathway inhibitory low molecular weight compounds on human mesenchymal stem cells. Cells)) treated with four kinds of low molecular weight compounds such as hexachlorophene, quercetin, ionomycin and PKF-115-584 (1) examination of proliferation ability (toxicity), (2) ability to inhibit Wnt / β-catenin pathway And (3) examination of hepatocyte differentiation ability.
<実施例1>
Luciferase発現ベクター安定導入株の構築(UE7T−13)
図1は、β−catenin/TCF4/ルシフェラーゼレポーター遺伝子を安定発現するヒト間葉系幹細胞の樹立方法について説明するための概念図である。図1に示すように、Luciferase発現ベクターを用いてpTCF4−CMVpro−GL4.20プラスミドを構築した。TCF4−CMVpro−GL4.20プラスミドは、3回繰り返しのTCF4配列CCTTTGATCをCMVプロモーターの上流に含み、luciferaseを発現する。また、pCMVpro−GL4.20プラスミドをコントロールとして構築した。得られたプラスミドをそれぞれ線状化し、UE7T−13にエレクトロポレーションによって導入し、培地中に加えたPuromycin(0.25μg/ml)によって選別した。Puromycin耐性の細胞はクローン化し、luciferaseアッセイに用いることにした。
<Example 1>
Construction of Luciferase expression vector stable introduction strain (UE7T-13)
FIG. 1 is a conceptual diagram for explaining a method of establishing human mesenchymal stem cells that stably express a β-catenin / TCF4 / luciferase reporter gene. As shown in FIG. 1, a pTCF4-CMVpro-GL4.20 plasmid was constructed using a Luciferase expression vector. The TCF4-CMVpro-GL4.20 plasmid contains the triple repeat TCF4 sequence CCTTGATC upstream of the CMV promoter and expresses luciferase. In addition, pCMVpro-GL4.20 plasmid was constructed as a control. Each of the obtained plasmids was linearized, introduced into UE7T-13 by electroporation, and selected by Puromycin (0.25 μg / ml) added to the medium. Puromycin-resistant cells were cloned and decided to be used for the luciferase assay.
<実施例2>
ヘキサクロロフェンによる分化誘導
本発明者らは、骨髄由来細胞(UE7T−13細胞)をヘキサクロロフェンで処理した場合について(1)増殖能(毒性)の検討、(2)Wnt/β−catenin経路抑制能の検討、(3)肝細胞分化能の検討を検討項目とした。
<Example 2>
Induction of differentiation by hexachlorophene The present inventors treated (1) proliferative ability (toxicity) and (2) ability to suppress Wnt / β-catenin pathway when bone marrow-derived cells (UE7T-13 cells) were treated with hexachlorophene. And (3) examination of hepatocyte differentiation ability.
(1)増殖能(毒性)の検討(MTTアッセイ(UE7T−13))
ヒト間葉系幹細胞株UE7T−13を細胞密度が9.0x103cells/cm2になるように96well plate(底面積:0.3cm2)に播種し、10%ウシ胎児血清(FBS,JRH Biosciences,INC)、100U/ml penicillin、100ug/ml streptomycin(Nacalai Tesque)を含むDulbecco’s Modified Eagle’s Medium (DMEM,ニッスイ)にて培養した。この時点をday0とする。翌日(day1)、ヘキサクロロフェンなどの低分子化合物を含むDMEMにメディウムチェンジした。以降、day2、day4、day8にTetraColor one(生化学工業)を用いて測定を行い、UE7T−13の細胞増殖への影響を検討した。培養液に含まれるDMSOは、終濃度が0.1%となるようにした。
(1) Examination of proliferation ability (toxicity) (MTT assay (UE7T-13))
Human mesenchymal stem cell line UE7T-13 was seeded in 96-well plate (bottom area: 0.3 cm 2 ) so that the cell density was 9.0 × 10 3 cells / cm 2 , and 10% fetal bovine serum (FBS, JRH Biosciences). , INC), 100 U / ml penicillin, 100 ug / ml streptomycin (Nacalai Tesque), and cultured in Dulbecco's Modified Eagle's Medium (DMEM, Nissui). This time is defined as day0. The next day (day 1), the medium was changed to DMEM containing a low molecular weight compound such as hexachlorophene. Thereafter, measurements were performed on Day2, day4, and day8 using TetraColor one (Seikagaku Corporation), and the effect of UE7T-13 on cell proliferation was examined. DMSO contained in the culture solution was adjusted to a final concentration of 0.1%.
骨髄由来細胞(UE7T−13細胞)をヘキサクロロフェンで処理した場合の結果を図2に示す。図2は、ヘキサクロロフェンによるWnt/β−catenin活性への影響を説明するためのグラフである。ヘキサクロロフェンで処理した場合には骨髄由来細胞(UE7T−13細胞)の増殖が有意に抑制されたが、増殖能自体は抑制された状態ではあるが維持されていた。すなわち、ヘキサクロロフェンによる骨髄由来細胞(UE7T−13細胞)への細胞毒性は十分に低く、分化誘導剤として使用可能な水準であることが判明した。特に、2μMでのヘキサクロロフェンによる骨髄由来細胞(UE7T−13細胞)への細胞毒性は非常に低いことが判明した。 The result at the time of processing a bone marrow origin cell (UE7T-13 cell) with hexachlorophene is shown in FIG. FIG. 2 is a graph for explaining the influence of hexachlorophene on Wnt / β-catenin activity. When treated with hexachlorophene, the growth of bone marrow-derived cells (UE7T-13 cells) was significantly suppressed, but the proliferation ability itself was maintained but maintained. That is, it has been found that the cytotoxicity of bone marrow-derived cells (UE7T-13 cells) by hexachlorophene is sufficiently low and can be used as a differentiation inducer. In particular, it was found that the cytotoxicity to bone marrow-derived cells (UE7T-13 cells) by hexachlorophene at 2 μM is very low.
(2)Wnt/β−catenin経路抑制能の検討(Luciferaseアッセイ(UE7T−13))
24well plateにLuciferase発現ベクター安定導入株を播種し、37℃で培養した。翌日、MTTアッセイの結果から細胞増殖に影響の無い濃度のヘキサクロロフェンなどの低分子化合物を含むメディウムに交換し、37℃で培養した。その後、1,4,8日後にluciferase活性をLuciferase Assay System(Promega)を使用し、556nmの波長を蛍光プレートリーダー(ARVIO)で測定した。
(2) Examination of Wnt / β-catenin pathway inhibitory ability (Luciferase assay (UE7T-13))
A 24-well plate was inoculated with a Luciferase expression vector stably introduced strain and cultured at 37 ° C. The next day, the medium was replaced with a medium containing a low molecular weight compound such as hexachlorophene at a concentration that does not affect cell growth based on the results of the MTT assay, and cultured at 37 ° C. Then, 1, 4, and 8 days later, luciferase activity was measured using a Luciferase Assay System (Promega), and a wavelength of 556 nm was measured with a fluorescence plate reader (ARVIO).
骨髄由来細胞(UE7T−13細胞)をヘキサクロロフェンで処理した場合の結果を図2に示す。その結果、pTCF4−CMVルシフェラーゼプラスミドによるレポーターアッセイにより、0.8μMでのヘキサクロロフェンによる骨髄由来細胞(UE7T−13細胞)を処理すると、ヘキサクロロフェン処理8日後にはWnt/β−cateninシグナルは有意に抑制されていることを確認した。 The result at the time of processing a bone marrow origin cell (UE7T-13 cell) with hexachlorophene is shown in FIG. As a result, when bone marrow-derived cells (UE7T-13 cells) were treated with hexachlorophene at 0.8 μM by reporter assay using pTCF4-CMV luciferase plasmid, Wnt / β-catenin signal was significantly increased after 8 days of hexachlorophene treatment. It was confirmed that it was suppressed.
(3)肝細胞分化能の検討
(3−1) 分化誘導(UE7T−13)
6well plateに細胞密度が9.0x103cells/cm2になるように播種し、37℃で24時間培養した。24時間後に、Luciferaseアッセイにより検討した濃度のヘキサクロロフェンなどの低分子化合物を含むメディウムに交換した。以降、週に2回培地交換し、週に1回継代して細胞数を9.0x103cells/cm2に調整した。誘導開始から8、16、24日目にTotal RNAを回収した。
(3) Examination of hepatocyte differentiation ability (3-1) Differentiation induction (UE7T-13)
The cells were seeded on a 6-well plate so that the cell density was 9.0 × 10 3 cells / cm 2 and cultured at 37 ° C. for 24 hours. After 24 hours, the medium was replaced with a medium containing a low molecular weight compound such as hexachlorophene at a concentration examined by Luciferase assay. Thereafter, the medium was changed twice a week, and the number of cells was adjusted to 9.0 × 10 3 cells / cm 2 by subculture once a week. Total RNA was collected on days 8, 16, and 24 from the start of induction.
(3−2) Reverse Transcription−Polymerase Chain Reaction(UE7T−13)
Total RNAは、TRIzol試薬で抽出した。抽出後、DNAを完全に除くため、Deoxyribonucleaseを加えて37℃で1時間インキュベートした。逆転写反応には、SuperScript First−Stand Synthesis System for RT−PCR(Invitrogen)を使用し、1μgのRNAをOligo dT PrimerにてcDNAへ変換した。PCRには、cDNAを5倍希釈し、そのうち1μlを使用した。PCR反応には、Taq DNA polymerase,recombinat(Invitrogen)を使用した。ヒトアルブミンのプライマーは、5’−TTGGAAAAATCCCACTGCAT−3’(配列番号:1)と5’−CTCCAAGCTGCTCAAAAAGC−3’(配列番号:2)を用いた。PCR反応は、95℃2分で1サイクル、95℃30秒、58℃30秒、72℃30秒で35サイクル施行した。内部対照としてヒトglyceradehyde 3−phosphate dehydrogenase(GAPDH)を用いた。GAPDHプライマーは、5’−GTCTTCTCCACCATGGAGAAGGCT−3’(配列番号:3)と5’−CATGCCAGTGAGCTTCCCGTTCA−3’(配列番号:4)を用いた。PCR反応は、95℃2分で1サイクル、95℃30秒、60℃30秒、72℃30秒で20サイクル施行した。PCR産物は、エチジウムブロマイドの入った2%アガロースゲルで30分間電気泳動し、トランスイルミネ―ターを用いて写真を撮った。
(3-2) Reverse Transcription-Polymerase Chain Reaction (UE7T-13)
Total RNA was extracted with TRIzol reagent. After extraction, in order to completely remove DNA, Deoxyribonuclease was added and incubated at 37 ° C. for 1 hour. In the reverse transcription reaction, SuperScript First-Stand Synthesis System for RT-PCR (Invitrogen) was used, and 1 μg of RNA was converted to cDNA by Oligo dT Primer. For PCR, cDNA was diluted 5-fold, 1 μl of which was used. Taq DNA polymerase, recombinat (Invitrogen) was used for PCR reaction. As the primer for human albumin, 5′-TTGGAAAAATCCCACTGCAT-3 ′ (SEQ ID NO: 1) and 5′-CTCCAAGCTGCTCAAAAAGC-3 ′ (SEQ ID NO: 2) were used. The PCR reaction was performed at 95 ° C. for 2 minutes for 1 cycle, 95 ° C. for 30 seconds, 58 ° C. for 30 seconds, and 72 ° C. for 30 seconds for 35 cycles. As an internal control, human glyceradehyde 3-phosphate dehydrogenase (GAPDH) was used. As GAPDH primers, 5′-GTCTTCTCACCCATGAGAAGAGCT-3 ′ (SEQ ID NO: 3) and 5′-CATGCCAGTGAGCTTCCCGTTCA-3 ′ (SEQ ID NO: 4) were used. The PCR reaction was performed at 95 ° C. for 2 minutes for 1 cycle, 95 ° C. for 30 seconds, 60 ° C. for 30 seconds, and 72 ° C. for 30 seconds for 20 cycles. PCR products were electrophoresed on a 2% agarose gel containing ethidium bromide for 30 minutes and photographed using a transilluminator.
図3は、ヘキサクロロフェンによる肝細胞分化誘導について説明するための電気泳動写真である。ヘキサクロロフェンによる処理の結果、肝細胞への分化誘導の代表的なマーカーであるアルブミン、AFP、GS、CYP1A1、TDO2などのマーカーの発現量がいずれもコントロールにくらべて明らかに増大していた。 FIG. 3 is an electrophoresis photograph for explaining the induction of hepatocyte differentiation by hexachlorophene. As a result of the treatment with hexachlorophene, the expression levels of markers such as albumin, AFP, GS, CYP1A1, and TDO2, which are representative markers for induction of differentiation into hepatocytes, were clearly increased as compared with the control.
(3−3)Immunocytochemistry(UE7T−13)
6well plateに70% EtOHで滅菌したカバーガラス(22x22mm,MATSUNAMI)を入れ、その上に細胞を播種し、ヘキサクロロフェンなどの低分子化合物を含む培地で培養した。培養開始から8,16,24日後にPBSで2回洗浄した後、4%パラホルムアルデヒド/PBSで細胞を20分間処理してカバーガラスに固定した。その後、0.2% Triton X−100で10分間透過処理した。3% BSA/PBSで30分間処理してブロッキングした。一次抗体としてanti−albumin antibody, anti−C/EBP antibody, anti−AFP antibody, anti−CYP1A1 antibodyを用い、4℃で一晩インキュベートした。次に、二次抗体としてAlexa Fluoro 488 goat anti−mouse antibody、Alexa Fluoro 594 goat anti−rabbit antibodyを用い、室温で1時間インキュベートした。核染色にDAPIを用いた。カバーガラスをPBSで希釈した50% glycerolで封入し、共焦点レーザー顕微鏡下で観察した。0.1% DMSOで培養した細胞をコントロールとした。
(3-3) Immunocytochemistry (UE7T-13)
Cover glass (22 × 22 mm, MATUNAMI) sterilized with 70% EtOH was placed on a 6-well plate, cells were seeded thereon, and cultured in a medium containing a low molecular compound such as hexachlorophene. After 8, 16, and 24 days from the start of the culture, the cells were washed twice with PBS, and the cells were treated with 4% paraformaldehyde / PBS for 20 minutes and fixed on a cover glass. Then, it was permeabilized with 0.2% Triton X-100 for 10 minutes. Blocked by treatment with 3% BSA / PBS for 30 minutes. Anti-albumin antibody, anti-C / EBP antibody, anti-AFP antibody, and anti-CYP1A1 antibody were used as primary antibodies and incubated overnight at 4 ° C. Next, Alexa Fluoro 488 goat anti-mouse antibody and Alexa Fluoro 594 goat anti-rabbit antibody were used as secondary antibodies and incubated at room temperature for 1 hour. DAPI was used for nuclear staining. The cover glass was sealed with 50% glycerol diluted with PBS, and observed under a confocal laser microscope. Cells cultured in 0.1% DMSO served as controls.
図4は、ヘキサクロロフェンによる肝細胞分化誘導(day8)について説明するための蛍光顕微鏡写真である。ヘキサクロロフェンによる肝細胞分化誘導を行った結果、ヘキサクロロフェンによる処理8日後には、肝細胞への分化誘導の代表的なマーカーであるアルブミン、C/EBPα、AFP、CYP1A1、TDO2などのマーカーの発現量がいずれもネガティブコントロール(0.1%DMSO)にくらべて明らかに増大して、ポジティブコントロール(肝癌細胞のHuH7)に近い量になっていた。図5は、ヘキサクロロフェンによる肝細胞分化誘導(day16)について説明するための蛍光顕微鏡写真である。ヘキサクロロフェンによる処理16日後についても、同様の結果を得た。 FIG. 4 is a fluorescence micrograph for explaining the induction of hepatocyte differentiation (day 8) by hexachlorophene. As a result of the induction of hepatocyte differentiation with hexachlorophene, expression of markers such as albumin, C / EBPα, AFP, CYP1A1, and TDO2, which are typical markers for induction of differentiation into hepatocytes, was observed 8 days after the treatment with hexachlorophene. Both amounts were clearly increased compared to the negative control (0.1% DMSO), and were close to the positive control (HuH7 of liver cancer cells). FIG. 5 is a fluorescence micrograph for explaining the induction of hepatocyte differentiation (day 16) by hexachlorophene. Similar results were obtained after 16 days of treatment with hexachlorophene.
(3−4)Periodic Acid−Schiff(PAS)染色(UE7T−13)
6well plateに70% EtOHで滅菌したカバーガラス(22x22mm,MATSUNAMI)を入れ、その上に細胞を播種し、ヘキサクロロフェンなどの低分子化合物を含む培地で培養した。培養開始から8,16,24日後にPBSで2回洗浄した後、4%パラホルムアルデヒド/PBSで細胞を20分間処理してカバーガラスに固定した。陰性対照として、10mg/mlのα−アミラーゼ(10mg/ml,0.1M リン酸緩衝液,pH6.8)で1時間、37℃でインキュベートしてグリコーゲンを消化した。1%過ヨウ素酸水溶液で10分間酸化処理した後、Schiff試薬で15分間処理してグリコーゲンを染色し、亜硫酸水溶液で3回、蒸留水で3回洗浄した。Mayer’s hematoxylinで核染色した後、カバーガラスをPBSで希釈した50% glycerolで封入し、光学顕微鏡下で観察した。0.1% DMSOで培養した細胞をコントロールとした。
(3-4) Periodic Acid-Schiff (PAS) staining (UE7T-13)
Cover glass (22 × 22 mm, MATUNAMI) sterilized with 70% EtOH was placed on a 6-well plate, cells were seeded thereon, and cultured in a medium containing a low molecular compound such as hexachlorophene. After 8, 16, and 24 days from the start of the culture, the cells were washed twice with PBS, and the cells were treated with 4% paraformaldehyde / PBS for 20 minutes and fixed on a cover glass. As a negative control, glycogen was digested by incubation with 10 mg / ml α-amylase (10 mg / ml, 0.1M phosphate buffer, pH 6.8) for 1 hour at 37 ° C. After oxidation with 1% periodic acid aqueous solution for 10 minutes, glycogen was stained by treatment with Schiff reagent for 15 minutes, washed 3 times with aqueous sulfurous acid solution and 3 times with distilled water. After nuclear staining with Mayer's hematoxylin, the cover glass was sealed with 50% glycerol diluted with PBS and observed under an optical microscope. Cells cultured in 0.1% DMSO served as controls.
図6は、ヘキサクロロフェンによる肝細胞分化誘導能(PAS染色)について説明するための顕微鏡写真である。ヘキサクロロフェンによる肝細胞分化誘導能(PAS染色)を行った結果、細胞内のグリコーゲンの蓄積量がいずれもネガティブコントロール(0.1%DMSO)にくらべて明らかに増大して、ポジティブコントロール(肝癌細胞のHuH7)と同等になっていた。 FIG. 6 is a photomicrograph for explaining the hepatocyte differentiation-inducing ability (PAS staining) by hexachlorophene. As a result of the ability to induce differentiation of hepatocytes by hexachlorophene (PAS staining), the amount of intracellular glycogen accumulation was clearly increased compared to the negative control (0.1% DMSO), and positive control (hepatoma cells) HuH7).
図7は、ヘキサクロロフェンによる肝細胞分化誘導能について説明するためのグラフである。図4、図5、図6の結果を定量化したうえで図7にまとめて示すが、ヘキサクロロフェンによる肝細胞分化誘導能(PAS染色)を行った結果、肝細胞への分化誘導の代表的なマーカーであるアルブミン、C/EBPα、CYP1A1などのマーカーの発現量がいずれもネガティブコントロール(0.1%DMSO)にくらべて明らかに増大して、ポジティブコントロール(肝癌細胞のHuH7)と同等になっていることにくわえて、ヘキサクロロフェンによる肝細胞分化誘導能(PAS染色)を行った結果、細胞内のグリコーゲンの蓄積量がいずれもネガティブコントロール(0.1%DMSO)にくらべて明らかに増大して、ポジティブコントロール(肝癌細胞のHuH7)と同等になっていることがわかる。これは、単に肝細胞マーカーを有するのみでなく、機能性肝機能としての能力をもつことを示している。 FIG. 7 is a graph for explaining the ability of hexachlorophene to induce hepatocyte differentiation. The results shown in FIGS. 4, 5, and 6 are quantified and collectively shown in FIG. 7. As a result of the ability to induce hepatocyte differentiation (PAS staining) by hexachlorophene, typical induction of differentiation into hepatocytes is shown. The expression levels of markers such as albumin, C / EBPα, and CYP1A1 are clearly increased compared to the negative control (0.1% DMSO), and are equal to the positive control (HuH7 of liver cancer cells). In addition, as a result of the ability to induce hepatocyte differentiation (PAS staining) with hexachlorophene, the amount of intracellular glycogen accumulation was clearly increased compared to the negative control (0.1% DMSO). It can be seen that this is equivalent to the positive control (HuH7 of liver cancer cells). This indicates that it has not only a hepatocyte marker but also a capability as a functional liver function.
(3−5)Ureaアッセイ(UE7T−13)
細胞を24well plateに播種し、ヘキサクロロフェンなどの低分子化合物を含む培地で培養した。メディウムに塩化アンモニウム(終濃度5mM)を加え、48,72,96時間培養後にメディウム中の尿素量をQuantiChrom Urea Assay Kit(BioAssay Systems)を使用し、520nmの波長を蛍光プレートリーダー(TECAN)を用いて測定した。
(3-5) Urea assay (UE7T-13)
The cells were seeded on a 24 well plate and cultured in a medium containing a low molecular compound such as hexachlorophene. Ammonium chloride (final concentration 5 mM) was added to the medium, and after culturing for 48, 72, 96 hours, the amount of urea in the medium was measured using a Quantum Chroma Assay Kit (BioAssay Systems) and a wavelength of 520 nm using a fluorescence plate reader (TECAN) Measured.
図8は、ヘキサクロロフェンによる分化誘導サンプルの尿素合成能(day8)について説明するためのグラフである。ヘキサクロロフェンによる肝細胞分化誘導能(尿素合成能測定)を8日間行った結果、細胞の尿素合成能がいずれもネガティブコントロール(0.1%DMSO)にくらべて明らかに増大して、ポジティブコントロール(肝癌細胞のHepG2)と同等になっていることがわかる。図9は、ヘキサクロロフェンによる分化誘導サンプルの尿素合成能(day16)について説明するためのグラフである。ヘキサクロロフェンによる肝細胞分化誘導能(尿素合成能測定)を16日間行った場合にも同様の結果が得られている。これは、単に肝細胞マーカーを有するのみでなく、機能性肝機能としての能力をもつことを示している。 FIG. 8 is a graph for explaining the urea synthesis ability (day 8) of a sample induced to differentiate by hexachlorophene. As a result of performing the hepatocyte differentiation-inducing ability (measurement of urea synthesis ability) with hexachlorophene for 8 days, the urea synthesis ability of the cells was clearly increased compared to the negative control (0.1% DMSO), and positive control ( It can be seen that it is equivalent to HepG2) of liver cancer cells. FIG. 9 is a graph for explaining the urea synthesis ability (day 16) of a differentiation-inducing sample with hexachlorophene. Similar results were obtained when hepatocyte differentiation induction ability (urea synthesis ability measurement) with hexachlorophene was performed for 16 days. This indicates that it has not only a hepatocyte marker but also a capability as a functional liver function.
<実施例3>
ケルセチンによる分化誘導
本発明者らは、2種類の細胞(骨髄由来細胞(UE7T−13細胞)、臍帯血由来細胞(UCBTERT−21細胞))をケルセチンで処理した場合について(1)増殖能(毒性)の検討、(2)Wnt/β−catenin経路抑制能の検討、(3)肝細胞分化能の検討を検討項目とした。なお、実施例2のヘキサクロロフェンでの実験と同様の点については説明の煩雑を避けるために省略している。
<Example 3>
Induction of differentiation by quercetin The present inventors treated the cells with two types of cells (bone marrow-derived cells (UE7T-13 cells) and umbilical cord blood-derived cells (UCBTERT-21 cells)) with quercetin. (2) Examination of Wnt / β-catenin pathway inhibitory ability and (3) Examination of hepatocyte differentiation ability. Note that the same points as in the experiment with hexachlorophene in Example 2 are omitted for the sake of simplicity.
増殖能(毒性)の検討
(1−1)骨髄由来細胞(UE7T−13細胞)の場合
図10は、ケルセチンによるWnt/β−catenin活性への影響(UE7T−13)について説明するためのグラフである。なお、実験方法は実施例2で既に説明したので繰り返さず結果のみ説明する。ケルセチンで処理した場合にも骨髄由来細胞(UE7T−13細胞)の増殖が有意に抑制されたが、増殖能自体は抑制された状態ではあるが維持されていた。すなわち、ケルセチンによる骨髄由来細胞(UE7T−13細胞)への細胞毒性は十分に低く、分化誘導剤として使用可能な水準であることが判明した。特に、5μMでのケルセチンによる骨髄由来細胞(UE7T−13細胞)への細胞毒性は非常に低いことが判明した。
Examination of proliferative ability (toxicity) (1-1) In the case of bone marrow-derived cells (UE7T-13 cells) FIG. 10 is a graph for explaining the influence (UE7T-13) of quercetin on Wnt / β-catenin activity. is there. Since the experimental method has already been described in Example 2, only the results will be described without being repeated. Proliferation of bone marrow-derived cells (UE7T-13 cells) was also significantly suppressed when treated with quercetin, but the proliferation ability itself was maintained although it was suppressed. That is, it was found that the cytotoxicity of bone marrow-derived cells (UE7T-13 cells) by quercetin is sufficiently low and can be used as a differentiation inducer. In particular, it was found that cytotoxicity to bone marrow-derived cells (UE7T-13 cells) by quercetin at 5 μM was very low.
(1−2)MTTアッセイ (UCBTERT−21)
ヒト臍帯血由来間葉系幹細胞株UCBTERT−21を細胞密度が2.0x103cells/cm2になるように96well plate(底面積:0.3cm2)に播種し、10%ウシ胎児血清(FBS,JRH Biosciences,INC)を含むMSCGM(三光純薬)にて培養した。この時点をday0とする。翌日(day1)、ケルセチンなどの低分子化合物を含むDMEMにメディウムチェンジした。以降、day2、day4、day8にTetraColor one(生化学工業)を用いて測定を行い、UCBTERT−21の細胞増殖への影響を検討した。培養液に含まれるDMSOは、終濃度が0.1%となるようにした。
(1-2) MTT assay (UCBTERT-21)
A human umbilical cord blood-derived mesenchymal stem cell line UCBTERT-21 was seeded on a 96-well plate (bottom area: 0.3 cm 2 ) so that the cell density was 2.0 × 10 3 cells / cm 2 , and 10% fetal bovine serum (FBS) was obtained. , JRH Biosciences, INC) and cultured with MSCGM (Sanko Junyaku). This time is defined as day0. The next day (day 1), the medium was changed to DMEM containing a low molecular compound such as quercetin. Thereafter, measurements were performed on Day2, day4, and day8 using TetraColor one (Seikagaku Corporation), and the influence of UCBTERT-21 on cell proliferation was examined. DMSO contained in the culture solution was adjusted to a final concentration of 0.1%.
図12は、ケルセチンによる細胞増殖能への影響(UCBTERT−21)について説明するためのグラフである。ケルセチンで処理した場合にも臍帯血由来細胞(UCBTERT−21細胞)の増殖が有意に抑制されたが、増殖能自体は抑制された状態ではあるが維持されていた。すなわち、ケルセチンによる臍帯血由来細胞(UCBTERT−21細胞)への細胞毒性は十分に低く、分化誘導剤として使用可能な水準であることが判明した。特に、6μMでのケルセチンによる臍帯血由来細胞(UCBTERT−21細胞)への細胞毒性は非常に低いことが判明した。 FIG. 12 is a graph for explaining the influence of quercetin on cell proliferation ability (UCBTERT-21). Even when treated with quercetin, the proliferation of cord blood-derived cells (UCBTERT-21 cells) was significantly suppressed, but the proliferation ability itself was suppressed but maintained. That is, it was found that the cytotoxicity of quercetin to umbilical cord blood-derived cells (UCBTERT-21 cells) is sufficiently low and can be used as a differentiation inducer. In particular, it was found that cytotoxicity to cord blood-derived cells (UCBTERT-21 cells) by quercetin at 6 μM was very low.
(2)Wnt/β−catenin経路抑制能の検討
(2−1)骨髄由来細胞(UE7T−13細胞)の場合
図10は、ケルセチンによるWnt/β−catenin活性への影響(UE7T−13)について説明するためのグラフである。なお、実験方法は実施例2で既に説明したので繰り返さず結果のみ説明する。TCF4−CMVルシフェラーゼプラスミドによるレポーターアッセイにより、1μMでのケルセチンによる骨髄由来細胞(UE7T−13細胞)を処理するとケルセチン処理8日後にはWnt/β−cateninシグナルは有意に抑制されていることを確認した。
(2) Examination of ability to suppress Wnt / β-catenin pathway (2-1) In case of bone marrow-derived cell (UE7T-13 cell) FIG. 10 shows the effect of quercetin on Wnt / β-catenin activity (UE7T-13) It is a graph for demonstrating. Since the experimental method has already been described in Example 2, only the results will be described without being repeated. It was confirmed by a reporter assay using TCF4-CMV luciferase plasmid that Wnt / β-catenin signal was significantly suppressed 8 days after quercetin treatment when bone marrow-derived cells (UE7T-13 cells) were treated with 1 μM quercetin. .
(2−2)Luciferaseアッセイ(UCBTERT−21)
24well plateにUCBTERT−21を細胞密度が2.0x103cells/cm2になるように播種し、37℃で24時間培養した。翌日、MTTアッセイの結果から細胞増殖に影響の無い濃度のケルセチンなどの低分子化合物を含むメディウムに交換し、37℃で培養した。その後、1,4,8日後にレポーター遺伝子をトランスフェクションした。トランスフェクションにはFugene6 Transfection Rreagent(Roche)を用いた。さらに24時間後に、luciferase活性をDual Luciferase Assay System(Promega)を使用してルシフェラーゼ活性を測定した。
(2-2) Luciferase assay (UCBTERT-21)
UCBTERT-21 was seeded on a 24-well plate so that the cell density was 2.0 × 10 3 cells / cm 2 and cultured at 37 ° C. for 24 hours. On the next day, the medium was replaced with a medium containing a low molecular weight compound such as quercetin at a concentration that does not affect cell growth based on the results of the MTT assay, and cultured at 37 ° C. Thereafter, the reporter gene was transfected 1, 4, and 8 days later. For transfection, Fugene6 Transfection Reagent (Roche) was used. Further, after 24 hours, luciferase activity was measured using Dual Luciferase Assay System (Promega).
図12は、ケルセチンによるWnt/β−catenin活性への影響について説明するためのグラフである。ケルセチンで処理した場合にも臍帯血由来細胞(UCBTERT−21細胞)の増殖が有意に抑制されたが、増殖能自体は抑制された状態ではあるが維持されていた。すなわち、ケルセチンによる臍帯血由来細胞(UCBTERT−21細胞)への細胞毒性は十分に低く、分化誘導剤として使用可能な水準であることが判明した。特に、5μMでのケルセチンによる臍帯血由来細胞(UCBTERT−21細胞)への細胞毒性は非常に低いことが判明した。また、pTCF4−CMVルシフェラーゼプラスミドによるレポーターアッセイにより、1μMでのケルセチンによる臍帯血由来細胞(UCBTERT−21細胞)を処理するとケルセチン処理8日後にはWnt/β−cateninシグナルは有意に抑制されていることを確認した。 FIG. 12 is a graph for explaining the influence of quercetin on Wnt / β-catenin activity. Even when treated with quercetin, the proliferation of cord blood-derived cells (UCBTERT-21 cells) was significantly suppressed, but the proliferation ability itself was suppressed but maintained. That is, it was found that the cytotoxicity of quercetin to umbilical cord blood-derived cells (UCBTERT-21 cells) is sufficiently low and can be used as a differentiation inducer. In particular, it was found that the cytotoxicity to cord blood-derived cells (UCBTERT-21 cells) by quercetin at 5 μM was very low. In addition, when umbilical cord blood-derived cells (UCBTERT-21 cells) were treated with quercetin at 1 μM by reporter assay using pTCF4-CMV luciferase plasmid, Wnt / β-catenin signal was significantly suppressed 8 days after quercetin treatment. It was confirmed.
(3)肝細胞分化能の検討
(3−1)骨髄由来細胞(UE7T−13細胞)の場合
図11は、ケルセチンによる肝細胞分化誘導能(UE7T−13)について説明するための電気泳動写真である。なお、実験方法は実施例2で既に説明したので繰り返さず結果のみ説明する。ケルセチンによる処理の結果、肝細胞への分化誘導の代表的なマーカーであるアルブミンの発現量がいずれもコントロールにくらべて明らかに増大していた。
(3−2)分化誘導(UCBTERT−21)
6well plateに細胞密度が2.0x103cells/cm2になるように播種し、37℃で24時間培養した。24時間後に、Luciferaseアッセイにより検討した濃度のケルセチンなどの低分子化合物を含むメディウムに交換した。以降、週に2回培地交換し、週に1回継代して細胞数を2.0x103cells/cm2に調整した。誘導開始から8、16、24日目にTotal RNAを回収した。
(3) Examination of hepatocyte differentiation ability (3-1) In case of bone marrow-derived cell (UE7T-13 cell) FIG. 11 is an electrophoresis photograph for explaining the hepatocyte differentiation inducing ability (UE7T-13) by quercetin. is there. Since the experimental method has already been described in Example 2, only the results will be described without being repeated. As a result of the treatment with quercetin, the expression level of albumin, which is a typical marker for inducing differentiation into hepatocytes, was clearly increased as compared with the control.
(3-2) Differentiation induction (UCBTERT-21)
The cells were seeded on a 6-well plate so that the cell density became 2.0 × 10 3 cells / cm 2 and cultured at 37 ° C. for 24 hours. After 24 hours, the medium was replaced with a medium containing a low molecular weight compound such as quercetin at the concentration studied by Luciferase assay. Thereafter, the medium was changed twice a week, and the number of cells was adjusted to 2.0 × 10 3 cells / cm 2 by subculture once a week. Total RNA was collected on days 8, 16, and 24 from the start of induction.
(3−3)Reverse Transcription−Polymerase Chain Reaction(UCBTERT−21)
Total RNAは、RNeasy Micro Kit(QIAGEN)を用いて抽出した。逆転写反応には、SuperScript First−Stand Synthesis System for RT−PCR(Invitrogen)を使用し、0.5μgのRNAをOligo dT PrimerにてcDNAへ変換した。PCRには、cDNAを5倍希釈し、そのうち1μlを使用した。PCR反応には、Taq DNA polymerase,recombinat(Invitrogen)を使用した。ヒトアルブミンのプライマーは、5’−TTGGAAAAATCCCACTGCAT−3’(配列番号:5)と5’−CTCCAAGCTGCTCAAAAAGC−3’(配列番号:6)を用いた。PCR反応は、95℃2分で1サイクル、95℃30秒、58℃30秒、72℃30秒で35サイクル施行した。内部対照としてヒトglyceradehyde 3−phosphate dehydrogenase(GAPDH)を用いた。GAPDHプライマーは、5’−GTCTTCTCCACCATGGAGAAGGCT−3’(配列番号:7)と5’−CATGCCAGTGAGCTTCCCGTTCA−3’(配列番号:8)を用いた。PCR反応は、95℃2分で1サイクル、95℃30秒、60℃30秒、72℃30秒で20サイクル施行した。PCR産物は、エチジウムブロマイドの入った2%アガロースゲルで30分間電気泳動し、トランスイルミネ―ターを用いて写真を撮った。
(3-3) Reverse Transaction-Polymerase Chain Reaction (UCBTERT-21)
Total RNA was extracted using RNeasy Micro Kit (QIAGEN). In the reverse transcription reaction, SuperScript First-Stand Synthesis System for RT-PCR (Invitrogen) was used, and 0.5 μg of RNA was converted to cDNA by Oligo dT Primer. For PCR, cDNA was diluted 5-fold, 1 μl of which was used. Taq DNA polymerase, recombinat (Invitrogen) was used for PCR reaction. As the primer for human albumin, 5′-TTGGAAAAATCCCACTGCAT-3 ′ (SEQ ID NO: 5) and 5′-CTCCAAGCTGCTCAAAAAGC-3 ′ (SEQ ID NO: 6) were used. The PCR reaction was performed at 95 ° C. for 2 minutes for 1 cycle, 95 ° C. for 30 seconds, 58 ° C. for 30 seconds, and 72 ° C. for 30 seconds for 35 cycles. As an internal control, human glyceradehyde 3-phosphate dehydrogenase (GAPDH) was used. As GAPDH primers, 5′-GTCTTCTCACCCATGAGAGAGGCT-3 ′ (SEQ ID NO: 7) and 5′-CATGCCAGTGAGCTTCCCGTTCA-3 ′ (SEQ ID NO: 8) were used. The PCR reaction was performed at 95 ° C. for 2 minutes for 1 cycle, 95 ° C. for 30 seconds, 60 ° C. for 30 seconds, and 72 ° C. for 30 seconds for 20 cycles. PCR products were electrophoresed on a 2% agarose gel containing ethidium bromide for 30 minutes and photographed using a transilluminator.
図13は、ケルセチンによる肝細胞分化誘導能(UCBTERT細胞)について説明するための電気泳動写真である。ケルセチンによる処理の結果、肝細胞への分化誘導の代表的なマーカーであるアルブミン、AFP、GS、CYP1A1、TDO2などのマーカーの発現量がいずれもコントロールにくらべて明らかに増大していた。図14は、ケルセチンによる肝細胞分化誘導能(UCBTERT細胞)について説明するための電気泳動写真である。ケルセチンによる処理の結果、肝細胞への分化誘導の代表的なマーカーであるアルブミン、EpCAMの発現量がコントロールにくらべて明らかに増大していた。 FIG. 13 is an electrophoretogram for explaining the ability of quercetin to induce hepatocyte differentiation (UCBTERT cells). As a result of treatment with quercetin, the expression levels of markers such as albumin, AFP, GS, CYP1A1, and TDO2, which are representative markers for induction of differentiation into hepatocytes, were clearly increased compared to the control. FIG. 14 is an electrophoresis photograph for explaining hepatocyte differentiation inducing ability (UCBTERT cells) by quercetin. As a result of treatment with quercetin, the expression levels of albumin and EpCAM, which are representative markers for induction of differentiation into hepatocytes, were clearly increased as compared with the control.
(3−4)Immunocytochemistry(UCBTERT−21)
図15は、ケルセチンによる肝細胞分化誘導(day24)について説明するための蛍光顕微鏡写真である。なお、実験方法はUE7T−13およびUCBTERT−21で共通であり、実施例2で既に説明したので繰り返さず結果のみ説明する。ケルセチンによる肝細胞分化誘導を行った結果、ケルセチンによる処理24日後には、肝細胞への分化誘導の代表的なマーカーであるアルブミン、C/EBPαなどのマーカーの発現量がいずれもネガティブコントロール(0.1%DMSO)にくらべて明らかに増大して、ポジティブコントロール(肝癌細胞のHuH7)に近い量になっていた。図16は、ケルセチンによる肝細胞分化誘導について説明するためのグラフである。図15の結果を定量化して示すと、ケルセチンによる処理24日後には、肝細胞への分化誘導の代表的なマーカーであるアルブミン、C/EBPαなどのマーカーの発現量がいずれもネガティブコントロール(0.1%DMSO)にくらべて明らかに増大していた。
(3-4) Immunocytochemistry (UCBTERT-21)
FIG. 15 is a fluorescence micrograph for explaining induction of hepatocyte differentiation (day 24) by quercetin. The experimental method is common to UE7T-13 and UCBTERT-21, and since it has already been described in Example 2, only the result will be described without being repeated. As a result of hepatocyte differentiation induction with quercetin, the expression levels of markers such as albumin and C / EBPα, which are representative markers for differentiation induction into hepatocytes, were negative control (0) after 24 days of treatment with quercetin. .. 1% DMSO) clearly increased to a level close to that of the positive control (HuH7 of liver cancer cells). FIG. 16 is a graph for explaining hepatocyte differentiation induction by quercetin. When the results of FIG. 15 are quantified, the expression levels of markers such as albumin and C / EBPα, which are typical markers for induction of differentiation into hepatocytes, are negative control (0) after 24 days of treatment with quercetin. .1% DMSO) was clearly increased.
(3−5)Ureaアッセイ(UCBTERT−21)
図17は、ケロセチンによる分化誘導サンプルの尿素合成能(day24)について説明するためのグラフである。なお、実験方法はUE7T−13およびUCBTERT−21で共通であり、実施例2で既に説明したので繰り返さず結果のみ説明する。ケロセチンによる肝細胞分化誘導能(尿素合成能測定)を24日間行った結果、尿素合成時間が48時間、ケロセチン投与量が5μMの条件では、細胞の尿素合成能がネガティブコントロール(0.1%DMSO)にくらべて有意に増大して、ポジティブコントロール(肝癌細胞のHepG2)と同等になっていることがわかる。これは、単に肝細胞マーカーを有するのみでなく、機能性肝機能としての能力をもつことを示している。
(3-5) Urea assay (UCBTERT-21)
FIG. 17 is a graph for explaining the urea synthesis ability (day 24) of a differentiation-inducing sample with kerosetin. The experimental method is common to UE7T-13 and UCBTERT-21, and since it has already been described in Example 2, only the result will be described without being repeated. As a result of performing the hepatocyte differentiation inducing ability (measurement of urea synthesis ability) with kerosetin for 24 days, the urea synthesis ability of the cells was negative control (0.1% DMSO) under the conditions of urea synthesis time of 48 hours and kerosetin dosage of 5 μM. ) Significantly increased compared to), and is equivalent to the positive control (HepG2 of liver cancer cells). This indicates that it has not only a hepatocyte marker but also a capability as a functional liver function.
<実施例4>
イオノマイシンによる分化誘導
本発明者らは、骨髄由来細胞(UE7T−13細胞)をイオノマイシンで処理した場合について(1)増殖能(毒性)の検討、(2)Wnt/β−catenin経路抑制能の検討、(3)肝細胞分化能の検討を検討項目とした。なお、実施例2のヘキサクロロフェンまたは実施例3のケルセチンでの実験と同様の点については説明の煩雑を避けるために省略している。
<Example 4>
Induction of differentiation by ionomycin The present inventors have examined (1) proliferative ability (toxicity) and (2) ability to suppress Wnt / β-catenin pathway when bone marrow-derived cells (UE7T-13 cells) are treated with ionomycin. (3) Examination of hepatocyte differentiation ability was set as an examination item. The same points as in the experiment with hexachlorophene of Example 2 or quercetin of Example 3 are omitted for the sake of simplicity.
(1)増殖能(毒性)の検討
図18は、イオノマイシンによる細胞増殖能への影響(UE7T−13)について説明するためのグラフである。なお、実験方法は実施例2で既に説明したので繰り返さず結果のみ説明する。イオノマイシンで処理した場合にも骨髄由来細胞(UE7T−13細胞)の増殖が有意に抑制されたが、増殖能自体は抑制された状態ではあるが維持されていた。すなわち、イオノマイシンによる骨髄由来細胞(UE7T−13細胞)への細胞毒性は十分に低く、分化誘導剤として使用可能な水準であることが判明した。特に、0.1μMでのイオノマイシンによる骨髄由来細胞(UE7T−13細胞)への細胞毒性は非常に低いことが判明した。
(1) Examination of proliferation ability (toxicity) FIG. 18: is a graph for demonstrating the influence (UE7T-13) on the cell proliferation ability by ionomycin. Since the experimental method has already been described in Example 2, only the results will be described without being repeated. Proliferation of bone marrow-derived cells (UE7T-13 cells) was also significantly suppressed when treated with ionomycin, but the proliferation ability itself was maintained but suppressed. That is, it was found that the cytotoxicity of bone marrow-derived cells (UE7T-13 cells) by ionomycin is sufficiently low and can be used as a differentiation inducer. In particular, it was found that the cytotoxicity of bone marrow-derived cells (UE7T-13 cells) by ionomycin at 0.1 μM is very low.
(2)Wnt/β−catenin経路抑制能の検討
図18は、イオノマイシンによるWnt/β−catenin活性への影響(UE7T−13)について説明するためのグラフである。なお、実験方法は実施例2で既に説明したので繰り返さず結果のみ説明する。TCF4−CMVルシフェラーゼプラスミドによるレポーターアッセイにより、0.01μMでのイオノマイシンによる骨髄由来細胞(UE7T−13細胞)を処理するとイオノマイシン処理8日後にはWnt/β−cateninシグナルは有意に抑制されていることを確認した。
(2) Examination of ability to suppress Wnt / β-catenin pathway FIG. 18 is a graph for explaining the influence (UE7T-13) on the Wnt / β-catenin activity by ionomycin. Since the experimental method has already been described in Example 2, only the results will be described without being repeated. By reporter assay using TCF4-CMV luciferase plasmid, it was confirmed that treatment of bone marrow-derived cells (UE7T-13 cells) with ionomycin at 0.01 μM significantly suppressed Wnt / β-catenin signal after 8 days of ionomycin treatment. confirmed.
(3)肝細胞分化能の検討
図11は、イオノマイシンによる肝細胞分化誘導能(UE7T−13)について説明するための電気泳動写真である。なお、実験方法は実施例2で既に説明したので繰り返さず結果のみ説明する。イオノマイシンによる処理の結果、肝細胞への分化誘導の代表的なマーカーであるアルブミンの発現量がいずれもコントロールにくらべて明らかに増大していた。
(3) Examination of hepatocyte differentiation ability FIG. 11: is an electrophoresis photograph for demonstrating the hepatocyte differentiation induction ability (UE7T-13) by ionomycin. Since the experimental method has already been described in Example 2, only the results will be described without being repeated. As a result of treatment with ionomycin, the expression level of albumin, which is a typical marker for inducing differentiation into hepatocytes, was clearly increased as compared with the control.
<実施例5>
PKF−115−584による分化誘導
本発明者らは、骨髄由来細胞(UE7T−13細胞)をPKF−115−584で処理した場合について(1)増殖能(毒性)の検討、(2)Wnt/β−catenin経路抑制能の検討、(3)肝細胞分化能の検討を検討項目とした。なお、実施例2のヘキサクロロフェン、実施例3のケルセチンまたは実施例4のイオノマイシンでの実験と同様の点については説明の煩雑を避けるために省略している。
<Example 5>
Induction of differentiation by PKF-115-584 The present inventors treated (1) proliferative ability (toxicity), (2) Wnt / when bone marrow-derived cells (UE7T-13 cells) were treated with PKF-115-584. The examination items were β-catenin pathway inhibitory ability and (3) hepatocyte differentiation ability. Note that the same points as in the experiment with hexachlorophene of Example 2, quercetin of Example 3 or ionomycin of Example 4 are omitted for the sake of simplicity.
(1)増殖能(毒性)の検討
図19は、PKF−115−584による増殖能への影響(UE7T−13)について説明するためのグラフである。なお、実験方法は実施例2で既に説明したので繰り返さず結果のみ説明する。PKF−115−584で処理した場合にも骨髄由来細胞(UE7T−13細胞)の増殖が有意に抑制されたが、増殖能自体は抑制された状態ではあるが維持されていた。すなわち、PKF−115−584による骨髄由来細胞(UE7T−13細胞)への細胞毒性は十分に低く、分化誘導剤として使用可能な水準であることが判明した。特に、5nMでのPKF−115−584による骨髄由来細胞(UE7T−13細胞)への細胞毒性は非常に低いことが判明した。
(1) Examination of proliferation ability (toxicity) FIG. 19: is a graph for demonstrating the influence (UE7T-13) on the proliferation ability by PKF-115-584. Since the experimental method has already been described in Example 2, only the results will be described without being repeated. Proliferation of bone marrow-derived cells (UE7T-13 cells) was also significantly suppressed when treated with PKF-115-584, but the proliferation ability itself was maintained, although maintained. That is, it was found that the cytotoxicity of bone marrow-derived cells (UE7T-13 cells) by PKF-115-584 is sufficiently low and is a level that can be used as a differentiation inducer. In particular, it was found that cytotoxicity to bone marrow-derived cells (UE7T-13 cells) by PKF-115-584 at 5 nM was very low.
(2)Wnt/β−catenin経路抑制能の検討
図19は、PKF−115−584によるWnt/β−catenin活性への影響(UE7T−13)について説明するためのグラフである。なお、実験方法は実施例2で既に説明したので繰り返さず結果のみ説明する。TCF4−CMVルシフェラーゼプラスミドによるレポーターアッセイにより、3nMでのPKF−115−584による骨髄由来細胞(UE7T−13細胞)を処理するとPKF−115−584処理8日後にはWnt/β−cateninシグナルは有意に抑制されていることを確認した。
(2) Examination of ability to suppress Wnt / β-catenin pathway FIG. 19 is a graph for explaining the influence (UE7T-13) on Wnt / β-catenin activity by PKF-115-584. Since the experimental method has already been described in Example 2, only the results will be described without being repeated. When the bone marrow-derived cells (UE7T-13 cells) were treated with PKF-115-584 at 3 nM by reporter assay using TCF4-CMV luciferase plasmid, Wnt / β-catenin signal was significantly increased after 8 days of PKF-115-584 treatment. It was confirmed that it was suppressed.
(3)肝細胞分化能の検討
図20は、PKF−115−584による肝細胞分化誘導能(UE7T−13)について説明するための電気泳動写真である。なお、実験方法は実施例2で既に説明したので繰り返さず結果のみ説明する。PKF−115−584による処理の結果、肝細胞への分化誘導の代表的なマーカーであるアルブミン、AFPの発現量がいずれもコントロールにくらべて明らかに増大していた。
(3) Examination of hepatocyte differentiation ability FIG. 20 is an electrophoresis photograph for explaining the hepatocyte differentiation inducing ability (UE7T-13) by PKF-115-584. Since the experimental method has already been described in Example 2, only the results will be described without being repeated. As a result of the treatment with PKF-115-584, the expression levels of albumin and AFP, which are representative markers for inducing differentiation into hepatocytes, were clearly increased compared to the control.
<結果の考察>
上記の実施例の実験結果から、本発明者らは、Wnt/β−カテニン経路を抑制する有機低分子量化合物を用いてヒト間葉系幹細胞を機能性肝細胞へ分化誘導可能であることを明らかにした。つまり、肝再生医療の実現化に向けて、間葉系幹細胞は肝再生医療の細胞ソースとして有用であり、さらに分化誘導時に有機低分子量化合物によるWnt/β−cateninシグナルの抑制が有効であることを明らかにした。これらは、真に臨床応用可能な肝再生医療の開発をしていく上で重要な知見であり、今後さらなる研究の進展が必要である。
<Consideration of results>
From the experimental results of the above examples, the present inventors have revealed that human mesenchymal stem cells can be induced to differentiate into functional hepatocytes using an organic low molecular weight compound that suppresses the Wnt / β-catenin pathway. I made it. That is, for the realization of liver regenerative medicine, mesenchymal stem cells are useful as a cell source for hepatic regenerative medicine, and further, it is effective to suppress Wnt / β-catenin signal with an organic low molecular weight compound during differentiation induction Was revealed. These are important findings for the development of truly clinically applicable liver regenerative medicine, and further research is needed in the future.
以上、本発明を実施例に基づいて説明した。この実施例はあくまで例示であり、種々の変形例が可能なこと、またそうした変形例も本発明の範囲にあることは当業者に理解されるところである。 In the above, this invention was demonstrated based on the Example. It is to be understood by those skilled in the art that this embodiment is merely an example, and that various modifications are possible and that such modifications are within the scope of the present invention.
たとえば、上記実施例では、4種類の有機低分子化合物に限定して説明したが、その他のWnt/β−cateninシグナルの抑制能を有する有機低分子化合物を用いてもよい。この場合にも、既に4種類の有機低分子化合物によって間葉系幹細胞を幹細胞に分化誘導できることが示されているので、当業者であればその他のWnt/β−cateninシグナルの抑制能を有する有機低分子化合物でも同様に間葉系幹細胞を幹細胞に分化誘導できることを理解できる。 For example, in the above-described examples, the description is limited to four kinds of organic low-molecular compounds, but other organic low-molecular compounds having the ability to suppress Wnt / β-catenin signals may be used. Also in this case, it has already been shown that mesenchymal stem cells can be induced to differentiate into stem cells by four kinds of organic low molecular weight compounds. It can be understood that low molecular weight compounds can induce differentiation of mesenchymal stem cells into stem cells as well.
Claims (7)
Wnt/β−カテニン経路を抑制する有機低分子量化合物を含み、
前記有機低分子量化合物が、ヘキサクロロフェン、ケルセチン、イオノマイシン、PKF115−584からなる群から選ばれる1種以上の化合物である、分化誘導剤。 An agent for inducing differentiation of mesenchymal stem cells into hepatocytes,
An organic low molecular weight compound that inhibits the Wnt / β-catenin pathway,
The organic low molecular weight compounds, hexachlorophene, quercetin, ionomycin, is at least one compound selected from the group consisting of PKF115-584, differentiation inducing agents.
前記有機低分子量化合物が、式(1)〜式(4)に示す化合物群から選ばれる1種以上の有機低分子量化合物である、分化誘導剤。
The organic low molecular weight compound is the formula (1) to one or more organic low molecular weight compound selected from the group of compounds shown in (4), differentiation inducing agents.
前記間葉系幹細胞が、骨髄由来細胞または臍帯血由来細胞である、分化誘導剤。 In the differentiation-inducing agent according to claim 1 or 2,
A differentiation inducer, wherein the mesenchymal stem cells are bone marrow-derived cells or cord blood-derived cells.
前記間葉系幹細胞におけるアルブミン、C/EBPα、CYPA1/A2およびAFPからなる群から選ばれる1種以上の蛋白質の発現を誘導する、分化誘導剤。 In the differentiation inducer according to any one of claims 1 to 3,
A differentiation inducer that induces the expression of one or more proteins selected from the group consisting of albumin, C / EBPα, CYPA1 / A2, and AFP in the mesenchymal stem cells.
前記間葉系幹細胞におけるグリコーゲン生産能または尿素合成能を増強する、分化誘導剤。 In the differentiation inducer according to any one of claims 1 to 4,
A differentiation inducer that enhances glycogen production ability or urea synthesis ability in the mesenchymal stem cells.
間葉系幹細胞を請求項1乃至5いずれかに記載の分化誘導剤で処理する工程を含む、分化誘導方法。 A method of inducing differentiation of hepatocytes from mesenchymal stem cells in vitro ,
A differentiation induction method comprising a step of treating mesenchymal stem cells with the differentiation inducer according to any one of claims 1 to 5.
前記分化誘導剤で処理する工程が、前記間葉系幹細胞を前記分化誘導剤で8日以上処理する工程を含む、分化誘導方法。 The differentiation induction method according to claim 6, wherein
The method of inducing differentiation, wherein the step of treating with the differentiation inducer comprises treating the mesenchymal stem cells with the differentiation inducer for 8 days or more.
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