JP2022545287A - Bcn057及びbcn512を用いる治療方法 - Google Patents
Bcn057及びbcn512を用いる治療方法 Download PDFInfo
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- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
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- 125000003367 polycyclic group Chemical group 0.000 description 1
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- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
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- 159000000001 potassium salts Chemical class 0.000 description 1
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- 125000002098 pyridazinyl group Chemical group 0.000 description 1
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- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
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- 238000010008 shearing Methods 0.000 description 1
- 102000035025 signaling receptors Human genes 0.000 description 1
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- 230000036556 skin irritation Effects 0.000 description 1
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- 201000002314 small intestine cancer Diseases 0.000 description 1
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- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
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- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000023895 stem cell maintenance Effects 0.000 description 1
- 230000002966 stenotic effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
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- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
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- 238000010189 synthetic method Methods 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 150000003511 tertiary amides Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000006169 tetracyclic group Chemical group 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- 208000023409 throat pain Diseases 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 230000025366 tissue development Effects 0.000 description 1
- 230000030968 tissue homeostasis Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000013706 tumor of meninges Diseases 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 206010046885 vaginal cancer Diseases 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 231100000747 viability assay Toxicity 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 208000010484 vulvovaginitis Diseases 0.000 description 1
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- 239000011701 zinc Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
Description
この出願は、2019年8月24日出願の米国仮特許出願第62/891,338号の優先権を主張するものである。前述の出願の内容は、参照により本明細書に組み込まれる。
癌は、体の他の部分に侵入又は拡散する可能性がある異常な細胞増殖を伴う疾患群として定義され得る。技術的に進歩しているにもかかわらず、癌は、死亡の重大な原因であり、かつ計り知れない苦しみであり続けている。癌は、米国で死亡の第2の最も一般的な原因である。
(式中:
R1は、アルキル、アルキルアミン、又はエーテルであり;
R2は、H又はCH3であり;かつ
R3は、H又はOHである)
の構造を有する化合物を投与することを含む、方法である。式Bの類似体は、本明細書に記載の式II、式III、式IV、式V、式VI、式VII、式VIII、式IX、式X、式XII、式XIII、式XIV、式XV、式XVI、式XVII、式XVIII及び式XIXを含んでよい。
(式中、
A5は、2級又は3級のアミン(すなわち、それによってスルホンアミドを形成する)であり、かつ
A6は、置換若しくは非置換のアリール又はヘテロアリール基であり、好ましくは、アリール又はヘテロアリール基は、置換された、例えば、スルホニルに遠位の位置に配置されたニトロを含む少なくとも1つの置換基を有する。特定の実施形態では、A5は、ピペリジン、ピペラジン、又はモルホリン環などの複素環式アミンであるが、他の実施形態では、アミンは非環式であり、かつ/又はスルホニルに結合される窒素原子は、A5に存在し得る任意の環に含まれない)
で表される化合物又はその医薬として許容される塩、エステル若しくはプロドラッグを提供する。
(式中;
Xは、N又は-CH-、好ましくはNであり;
Y1及びY2は、それぞれ独立して低級アルキルであるか、又はY1及びY2は、Xと共に、
(式中、
Xは、N、C又はCHであり;
Gは、N、C又はCHであり;
Zは、存在しないか、又は置換若しくは非置換のアルキル、ヘテロアルキル、アルケニル、又はアルキニルから選択され;かつ
R4は、水素であるか、又は置換若しくは非置換のアリール(例えば、フェニル)及びヘテロアリールから選択され、かつ
R5及びR6は、各々独立して、存在しないか、又は低級アルキルである)
などのヘテロシクリル環系を形成する)
で表される化合物又はその医薬として許容される塩、エステル若しくはプロドラッグを提供する。
(式中、
Xは-C(H)-であり、かつ
R4は、ハロゲン置換フェニル基、例えば、4-フルオロフェニル又は3-クロロフェニルなどの置換又は非置換アリール(例えば、フェニル)及びヘテロアリール)から選択される)
を形成する。特定の実施形態では、Y1及びY2は、各々エチルである。特定の好ましい実施形態では、Y1及びY2は、共にピペラジン環を形成する。特定の好ましい実施形態では、Zは存在しない。
(式中、
R1=ハロゲン、N、OH、CH3、OH、(CH2)n-CH3又は置換もしくは非置換のアリール;
R2=ハロゲン、N、OH、CH3、OH、(CH2)n-CH3又は置換もしくは非置換のアリール;
R3=ハロゲン、N、OH、CH3、OH、(CH2)n-CH3又は置換もしくは非置換のアリール;
R4=ハロゲン、N、OH、CH3、OH、(CH2)n-CH3又は置換もしくは非置換のアリール)
の化合物又はその類似体である。類似体は、式XXII、式XXIII、式XXIV、式XXV、式XXVI及び式XXVIIの化合物を含み得る。
「1つの実施形態/態様」又は「一実施形態/態様」への本明細書における言及は、実施形態/態様に関連して記載される特定の特性、構造、又は特徴が本開示の少なくとも1つの実施形態/態様に含まれることを意味する。本明細書の様々な場所での語句「1つの実施形態/態様」又は「別の実施形態/態様」の使用は、必ずしも全てが同一の実施形態/態様を参照するものではなく、他の実施形態/態様を除いて、互いに別々の又は代替的な実施形態/態様を参照するものでもない。さらに、いくつかの実施形態/態様によって示され、かつ他の実施形態では示され得ない、様々な特性が記載される。同様に、いくつかの実施形態/態様についての要件であり得るが、他の実施形態/態様ではあり得ない、様々な要件が記載されている。実施形態及び態様は、特定の場合に互換的に使用され得る。
前述の一般的な説明と以下の詳細な説明の両方は、例示的で、説明的であり、特許請求の範囲に記載される本技術のさらなる説明を提供することを意図するものであることを理解されたい。本技術のさらなる特徴及び利点は、以下の説明に記載されており、一部は説明から明らかであるか、又は本技術を実施することによって学習され得る。本技術の利点は、本明細書の記載及びその特許請求の範囲で特に指摘された構造によって実現され、達成されるであろう。
BCN057は、YEL002としても知られ、下記構造式で表される:
それは、(3-[(フラン-2-イルメチル)アミノ]-2-(7-メトキシ-2-オキソ-1,2-ジヒドロキノリン-3-イル)-6-メチルイミダゾ[1,2-a]ピリジン-1-イウム)としても記載され得る。本発明は、BCN057の化合物、その類似体及びそれらの塩を包含することが理解されるであろう。一実施形態では、本発明は、遊離塩基の形態のBCN057の化合物に関する。別の実施形態では、本発明は、BCN057の化合物又はその医薬として許容される塩に関する。
(式中、
R1は、アルキル、アルキルアミン、又はエーテルであり;
R2は、H又はCH3であり;かつ
R3は、H又はOHである)
の構造を有する化合物を投与することを含む、治療の方法を含む。
本明細書に記載の化合物は、本発明の方法において有用であり、理論に拘束されないが、Wntβ-カテニンシグナル伝達を調節する能力を介して部分的に、それらの望ましい効果を発揮すると考えられる。Wnt経路は、胚における組織の発達及び成人における組織の維持に関与する。これは、細胞の成長、移動及び細胞生存を制御する遺伝子の特定のセットを制御する。これらの遺伝子の慢性活性化及びWnt経路の異常な活性化は、制御されない細胞増殖及び生存をもたらし、結果的に、結腸、皮膚、肝臓及び卵巣を含む組織の範囲で癌の形成を促進し得る。
研究は、Wnt経路が、遺伝性家族性大腸ポリポーシス及び結腸癌の自発的形態の両方において恒久的に活性化されることを実証した。これらの細胞におけるWnt経路の慢性的な活性化は、良性アデノーマ(ポリープとも呼ばれる)へのそれらの拡大を促進し、これはしばしば侵襲性大腸癌に進行する。散発性結腸癌の約90%が、通常APCにおける変異の結果として、異常なWntシグナル伝達活性を示す。
BCN057は、癌、特に膵臓及び胃腸(GI)癌の治療に有効である。一態様では、それを必要とする対象において放射線誘発性胃腸症候群(RIGS)を治療する方法であって、対象に治療有効量のBCN057の化合物又はBCN057の類似体を投与する工程を含む、方法が、本明細書で開示される。類似体は、式II~XIXの化合物の1以上であり得る。BCN057は、RIGSを緩和し、腹部放射線療法のための治療比率を向上させることができる。さらに、BCN057は、口腔粘膜炎、GI粘膜炎、例えば、喉、胃及び腸、腸炎及び乳房炎を含む、放射線誘発粘膜炎を緩和する。さらに、それは、放射線及び化学療法からの上皮組織の損傷を防止及び治療できる。これらの化合物は、放射線治療と関連付けられるこれらの放射線症候群の治療又は予防にも有用である。
併用療法は、異なる機構によって作用する薬物と共に特に有効であり、それによって抵抗性癌細胞が発生する可能性を減少させる。効果の異なる薬物が組み合わされる場合、各薬物は、許容できない副作用を生じることなく、最適な用量で使用され得る。BCN057と第2の薬剤を、治療効果のために組み合わせることができる。第2の薬剤は、異なる機構を有してよい。あるいは、それは、治療効果のためにBCN057と同じ機構を使用できる。この組み合わせは、相乗効果を介して作用できる。併用療法はまた、追加(例えば、第3、第4、第5など)の薬剤を含んでよい。BCN512は、同様に併用療法において使用できる。
多くの結腸癌は、分泌されるFzd関連タンパク質(SFRP)又はWnt阻害因子(WIF)ファミリーのメンバーをコードするサイレント遺伝子を担持し、それらはWnt経路の自然ブレーキとして作用する。それらは、Wntリガンドと結合して、細胞表面での経路活性化を阻止できる。この阻害なしに、癌細胞により生成されるWntリガンドは、膜における経路を活性化し、APC、β-カテニン又はAxin2の変異によって開始される異常なWntシグナル伝達活性を増幅できる。この異常Wnt経路活性化は、癌につながる可能性がある。
BCN512は、炎症性疾患又は状態を治療するために使用できる。炎症性皮膚疾患は、乾癬、湿疹及び皮膚炎などの細胞増殖に関連付けられる病態(例えば、湿疹性皮膚炎、局所及び脂漏性皮膚炎、アレルギー性又は刺激性接触皮膚炎、亀裂性湿疹、光アレルギー性皮膚炎、光毒性皮膚炎、植物性光線皮膚炎、放射性皮膚炎、及びうっ滞性皮膚炎)を含む。他の炎症性皮膚疾患は、皮膚又は粘膜の外傷、火傷、水疱性障害、又は虚血に起因する強皮症、潰瘍及び侵食、いくつかの形態の魚鱗癬、表皮水疱症、肥厚性瘢痕、ケロイド、内因性老化の皮膚の変化、光老化、皮膚の機械的せん断に起因する摩擦による水ぶくれ、及びコルチコステロイドの局所使用に起因する皮膚萎縮を含むが、これらに限定されない。さらなる炎症性皮膚状態は、口唇炎、唇の荒れ、鼻の炎症、粘膜炎及び外陰膣炎などの粘膜の炎症を含む。
さらなる実施形態は、ウイルス感染の治療のためのBCN057及びBCN057の類似体の使用を含む。ウイルス疾患感染症は、病原性ウイルスが身体に侵入した時に生じ、感染性ウイルス粒子は、感受性細胞に付着し侵入する。宿主免疫応答は、疾患及び過剰な炎症を媒介できる。ウイルス感染に応答した自然免疫系及び獲得免疫系の刺激は、感染細胞を破壊し、宿主にとって重篤な病理学的結果(すなわち、ウイルス誘発免疫病理)をもたらし得る。具体的には、免疫病理は、抗体、インターフェロン及び炎症性サイトカインの過剰な放出、補体系の活性化、又は細胞傷害性T細胞の過活動により引き起こされる。インターフェロン及び他のサイトカインの分泌は、細胞の損傷、発熱及びインフルエンザ様の症状を引き起こし得る。2005年のトリH5N1インフルエンザのように、特定のウイルス感染の重篤な症例において、宿主免疫応答の異常な誘導は、サイトカインストームとして知られるサイトカインのフレア放出を誘発できる。
さらなる実施形態は、うつ病の治療のためのBCN057及びBCN057の類似体の使用を含む。Wntシグナル伝達はまた、うつ病を治療するのに重要である。1950年代以降、炭酸リチウムと他の塩は、うつ病を治療するために同様に使用されてきた。リチウムは、wnt下流シグナル経路中のGSK3bを阻害すること、およびβ-カテニン下流遺伝子を転写することにより作用する。
図1は、膵臓癌細胞株の生存率に対する5-FU及びBCN057の効果を示す。膵臓癌細胞株の生存率に対する5-FU及びBCN057の効果を、ATP Liteアッセイ(Perkin Elmer)により評価した。50uMの5Fu(5Fu、n=5)、50uMの5Fu並びに2、5、10、及び20uMのBCN057(5Fu+BCN057、n=5)、又は2、5、10、20uMのCN057(CN057、n=5)。対照細胞(V、n=5)。リン酸化率を、各状態の平均値を各時点での対照細胞(V)の平均値で除することにより算出した。
線維症は、結合組織が正常な実質組織をチェックされない程度に置き換え、かなりの組織リモデリング及び永久瘢痕組織の形成をもたらす、病理学的創傷治癒として一般的に定義される。肺線維症は、肺組織が損傷され瘢痕化されるときに生じる、肺疾患である。本明細書(par.095)で説明されるように、身体のあらゆる器官は、一般に線維化病変をもたらす修復応答を開始できる。肝炎感染による慢性閉塞性肺疾患及び肝線維症の結果としての肺線維症が、2つの例である。
本発明の方法は、疾患若しくは病態、又は疾患若しくは病態の1以上の症状を防止し得る。本明細書で使用する場合、障害又は病態を「予防する」治療薬は、統計サンプルにおいて、未治療対照サンプルに対し治療済みサンプル中の障害又は病態の発生を低下させるか、又は未治療対照サンプルに対し障害又は病態の1以上の症状の発症を遅らせるか重症度を低下させる、化合物を指す。
Claims (25)
- 対象における癌を治療する方法であって、式Bの化合物又はその類似体の治療有効量を前記対象に投与することを含む、方法。
- 前記癌が、膀胱癌、脳癌、乳癌、結腸直腸癌、子宮頸癌、胃腸癌、泌尿生殖器癌、頭頸部癌、肺癌、卵巣癌、膵臓癌、前立腺癌、腎癌、直腸癌、皮膚癌、血液癌又は精巣癌のうちの少なくとも1つである、請求項3に記載の方法。
- 前記方法が、前記対象に1種以上の追加の薬剤を投与することをさらに含む、請求項3に記載の方法。
- 前記方法が、前記対象に化学療法又は放射線療法を施すことをさらに含む、請求項3に記載の方法。
- 化学療法又は放射線療法の副作用を1つ以上有する対象を治療する方法であって、式Bの化合物又はその類似体の治療有効量を前記対象に投与することを含む、方法。
- それを必要とする対象における上皮細胞への放射線誘発損傷を予防又は治療する方法であって、式Bの化合物又はその類似体の治療有効量を前記対象に投与する工程を含む、方法。
- 上皮細胞への前記放射線誘発損傷が、放射線誘発性胃腸症候群(RIGS)、放射線誘発性粘膜炎、放射線誘発性口腔粘膜炎、放射線誘発性直腸炎又は放射線誘発性腸炎のうちの1つ以上として特定される、請求項8に記載の方法。
- 対象における線維症を治療する方法であって、式Bの化合物又はその類似体の治療有効量を前記対象に投与することを含む、方法。
- 前記線維症が、肺線維症、特発性肺線維症、急性呼吸窮迫症候群、嚢胞性線維症、非嚢胞性線維症気管支拡張症、肝硬変、肝線維症、心内膜心筋線維症、陳旧性心筋梗塞、心房線維症、縦隔線維症、骨髄線維症、後腹膜線維症、進行性塊状線維症、腎性全身性線維症、クローン病、胃腸線維症、ケロイド状態、強皮症/全身性硬化症、関節線維症、ペイロニー病、デュピュイトラン拘縮、口腔粘膜下線維症、肝線維症、胃腸線維症、腎臓透析による腎線維症又は癒着性関節包炎である、請求項10に記載の方法。
- それを必要とする対象におけるウイルス感染を治療する方法であって、式Bの化合物又はその類似体の治療有効量を前記対象に投与する工程を含む、方法。
- それを必要とする対象におけるうつ病を治療する方法であって、式Bの化合物又はその類似体の治療有効量を前記対象に投与する工程を含む、方法。
- 対象における炎症を治療する方法であって、式XXIの化合物又はその類似体の治療有効量を前記対象に投与することを含み、
前記類似体が、式XXII、式XXIII、式XXIV、式XXV、式XXVI及び式XXVIIから選択される、
方法。 - 対象における疾患を治療するためにWnt活性を調節する方法であって、式XXIの化合物又はその類似体の治療有効量を前記対象に投与することを含み、
前記類似体が、式XXII、式XXIII、式XXIV、式XXV、式XXVI及び式XXVIIから選択される、方法。 - 前記疾患が、放射線被爆、線維症、インスリン感受性、癌、骨粗鬆症、脱毛/発毛、創傷治癒、低骨密度及び肥満のうちの少なくとも1つである、請求項16に記載の方法。
- 前記線維症が、肺線維症、特発性肺線維症、急性呼吸窮迫症候群、嚢胞性線維症、非嚢胞性線維症気管支拡張症、肝硬変、肝線維症、心内膜心筋線維症、陳旧性心筋梗塞、心房線維症、縦隔線維症、骨髄線維症、後腹膜線維症、進行性塊状線維症、腎性全身性線維症、クローン病、胃腸線維症、ケロイド状態、強皮症/全身性硬化症、関節線維症、ペイロニー病、デュピュイトラン拘縮、口腔粘膜下線維症、肝線維症、胃腸線維症、腎臓透析による腎線維症又は癒着性関節包炎である、請求項17に記載の方法。
- 前記疾患が、放射線被爆、線維症、インスリン感受性、癌、骨粗鬆症、脱毛/発毛、創傷治癒、低骨密度及び肥満のうちの少なくとも1つである、請求項19に記載の方法。
- 前記疾患が、化学療法又は放射線療法の1以上の副作用である、請求項19に記載の方法。
- 前記疾患が、放射線被爆、線維症、インスリン感受性、癌、骨粗鬆症、脱毛/発毛、創傷治癒、低骨密度及び肥満のうちの少なくとも1つである、請求項22に記載の方法。
- 前記線維症が、肺線維症、特発性肺線維症、急性呼吸窮迫症候群、嚢胞性線維症、非嚢胞性線維症気管支拡張症、肝硬変、肝線維症、心内膜心筋線維症、陳旧性心筋梗塞、心房線維症、縦隔線維症、骨髄線維症、後腹膜線維症、進行性塊状線維症、腎性全身性線維症、クローン病、胃腸線維症、ケロイド状態、強皮症/全身性硬化症、関節線維症、ペイロニー病、デュピュイトラン拘縮、口腔粘膜下線維症、肝線維症、胃腸線維症、腎臓透析による腎線維症又は癒着性関節包炎である、請求項23に記載の方法。
- 前記疾患が、化学療法又は放射線療法の1以上の副作用である、請求項22に記載の方法。
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