JP2019537585A5 - - Google Patents
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- JP2019537585A5 JP2019537585A5 JP2019522841A JP2019522841A JP2019537585A5 JP 2019537585 A5 JP2019537585 A5 JP 2019537585A5 JP 2019522841 A JP2019522841 A JP 2019522841A JP 2019522841 A JP2019522841 A JP 2019522841A JP 2019537585 A5 JP2019537585 A5 JP 2019537585A5
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- JP
- Japan
- Prior art keywords
- ezh2
- divalent
- cancer
- alkyl
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000001875 compounds Chemical class 0.000 claims description 71
- 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 claims description 65
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 40
- 206010028980 Neoplasm Diseases 0.000 claims description 35
- 201000011510 cancer Diseases 0.000 claims description 27
- 230000001404 mediated effect Effects 0.000 claims description 25
- 230000015556 catabolic process Effects 0.000 claims description 18
- 238000006731 degradation reaction Methods 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 239000003446 ligand Substances 0.000 claims description 16
- 239000003623 enhancer Substances 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 claims description 11
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 claims description 11
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 208000026310 Breast neoplasm Diseases 0.000 claims description 6
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 5
- 238000011269 treatment regimen Methods 0.000 claims description 5
- FKSFKBQGSFSOSM-QFIPXVFZSA-N 1-[(2S)-butan-2-yl]-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-methyl-6-[6-(1-piperazinyl)-3-pyridinyl]-4-indolecarboxamide Chemical compound C1=C2N([C@@H](C)CC)C=C(C)C2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C(C=N1)=CC=C1N1CCNCC1 FKSFKBQGSFSOSM-QFIPXVFZSA-N 0.000 claims description 4
- ZOIBZSZLMJDVDQ-UHFFFAOYSA-N 1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[4-(4-morpholinylmethyl)phenyl]-4-indazolecarboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(C=2C=CC(CN3CCOCC3)=CC=2)=CC2=C1C=NN2C1CCCC1 ZOIBZSZLMJDVDQ-UHFFFAOYSA-N 0.000 claims description 4
- SZAYCVHJDOWSNY-UHFFFAOYSA-N 3-[ethyl(oxan-4-yl)amino]-2-methyl-N-[(1-methyl-3-oxo-5,6,7,8-tetrahydro-2H-isoquinolin-4-yl)methyl]-5-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]benzamide Chemical compound CCN(C1CCOCC1)c1cc(cc(C(=O)NCc2c3CCCCc3c(C)[nH]c2=O)c1C)-c1ccc(nc1)N1CCN(C)CC1 SZAYCVHJDOWSNY-UHFFFAOYSA-N 0.000 claims description 4
- RXCVUHMIWHRLDF-HXUWFJFHSA-N 5,8-dichloro-2-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-7-[(R)-methoxy(oxetan-3-yl)methyl]-3,4-dihydroisoquinolin-1-one Chemical compound ClC1=C2CCN(C(C2=C(C(=C1)[C@@H](C1COC1)OC)Cl)=O)CC=1C(NC(=CC=1OC)C)=O RXCVUHMIWHRLDF-HXUWFJFHSA-N 0.000 claims description 4
- PFHDWRIVDDIFRP-UHFFFAOYSA-N 6-cyano-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-pentan-3-ylindole-4-carboxamide Chemical compound C1=C(C#N)C=C2N(C(CC)CC)C=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O PFHDWRIVDDIFRP-UHFFFAOYSA-N 0.000 claims description 4
- ULNXAWLQFZMIHX-UHFFFAOYSA-N GSK343 Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3C=C(C=2)C=2C=C(N=CC=2)N2CCN(C)CC2)C(C)C)=C1CCC ULNXAWLQFZMIHX-UHFFFAOYSA-N 0.000 claims description 4
- LQTWDAYNGMMHLV-UHFFFAOYSA-N N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-6-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(nc2n(ncc12)C(C)C)-c1ccc(nc1)N1CCN(C)CC1 LQTWDAYNGMMHLV-UHFFFAOYSA-N 0.000 claims description 4
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 4
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 claims description 4
- 229940125961 compound 24 Drugs 0.000 claims description 4
- NSQSAUGJQHDYNO-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methyl-5-[4-(morpholin-4-ylmethyl)phenyl]benzamide Chemical compound C=1C(C=2C=CC(CN3CCOCC3)=CC=2)=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C)C=1N(CC)C1CCOCC1 NSQSAUGJQHDYNO-UHFFFAOYSA-N 0.000 claims description 4
- XQFINGFCBFHOPE-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-[ethyl-[4-[2-methoxyethyl(methyl)amino]cyclohexyl]amino]-2-methyl-5-(3-morpholin-4-ylprop-1-ynyl)benzamide Chemical compound C=1C(C#CCN2CCOCC2)=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C)C=1N(CC)C1CCC(N(C)CCOC)CC1 XQFINGFCBFHOPE-UHFFFAOYSA-N 0.000 claims description 4
- PFPSFENQCNMITC-MRXNPFEDSA-N n-[(4-methoxy-6-methyl-2-oxo-1h-pyridin-3-yl)methyl]-2-methyl-1-[(1r)-1-(oxan-4-yl)ethyl]indole-3-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C3=CC=CC=C3N([C@H](C)C3CCOCC3)C=2C)=C1OC PFPSFENQCNMITC-MRXNPFEDSA-N 0.000 claims description 4
- HPODOLXTMDHLLC-QGZVFWFLSA-N n-[(4-methoxy-6-methyl-2-oxo-1h-pyridin-3-yl)methyl]-2-methyl-1-[(1r)-1-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]ethyl]indole-3-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C3=CC=CC=C3N([C@H](C)C3CCN(CC(F)(F)F)CC3)C=2C)=C1OC HPODOLXTMDHLLC-QGZVFWFLSA-N 0.000 claims description 4
- DPJNKUOXBZSZAI-UHFFFAOYSA-N n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-[6-(4-propan-2-ylpiperazin-1-yl)pyridin-3-yl]indazole-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3C=C(C=2)C=2C=NC(=CC=2)N2CCN(CC2)C(C)C)C(C)C)=C1CCC DPJNKUOXBZSZAI-UHFFFAOYSA-N 0.000 claims description 4
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 206010057444 Oropharyngeal neoplasm Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 206010038111 Recurrent cancer Diseases 0.000 claims description 3
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 3
- 125000002015 acyclic group Chemical group 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 150000001721 carbon Chemical class 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 208000022136 colorectal lymphoma Diseases 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 238000000354 decomposition reaction Methods 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 claims description 3
- 229960004942 lenalidomide Drugs 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 230000003211 malignant effect Effects 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical compound NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 claims description 3
- 229960000688 pomalidomide Drugs 0.000 claims description 3
- 208000015347 renal cell adenocarcinoma Diseases 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 125000003003 spiro group Chemical group 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 229960003433 thalidomide Drugs 0.000 claims description 3
- 210000001519 tissue Anatomy 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 206010046766 uterine cancer Diseases 0.000 claims description 3
- CAICZZJHNJHHDJ-UHFFFAOYSA-N 1-(4,4,5,5,5-pentafluoropentylsulfinyl)nonane Chemical compound CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F CAICZZJHNJHHDJ-UHFFFAOYSA-N 0.000 claims description 2
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims description 2
- -1 Compound 3 Chemical compound 0.000 claims description 2
- 102000003960 Ligases Human genes 0.000 claims description 2
- 108090000364 Ligases Proteins 0.000 claims description 2
- 102100032783 Protein cereblon Human genes 0.000 claims description 2
- 101000776133 Viola hederacea Leaf cyclotide 1 Proteins 0.000 claims description 2
- 238000002512 chemotherapy Methods 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 229940125877 compound 31 Drugs 0.000 claims description 2
- 238000001794 hormone therapy Methods 0.000 claims description 2
- 125000001165 hydrophobic group Chemical group 0.000 claims description 2
- 238000009169 immunotherapy Methods 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 238000001959 radiotherapy Methods 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 1
- 0 *C(c1c(C2*)c(*)ccc1)N2C(CCC(N1)=O)C1=O Chemical compound *C(c1c(C2*)c(*)ccc1)N2C(CCC(N1)=O)C1=O 0.000 description 5
- 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
- 201000006958 oropharynx cancer Diseases 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662414195P | 2016-10-28 | 2016-10-28 | |
| US62/414,195 | 2016-10-28 | ||
| PCT/US2017/058718 WO2018081530A1 (en) | 2016-10-28 | 2017-10-27 | Compositions and methods for treating ezh2-mediated cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2019537585A JP2019537585A (ja) | 2019-12-26 |
| JP2019537585A5 true JP2019537585A5 (https=) | 2021-09-16 |
Family
ID=62024052
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019522841A Pending JP2019537585A (ja) | 2016-10-28 | 2017-10-27 | Ezh2媒介性がんを治療するための組成物および方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US20190255041A1 (https=) |
| EP (1) | EP3532464A4 (https=) |
| JP (1) | JP2019537585A (https=) |
| KR (1) | KR20190084063A (https=) |
| CN (1) | CN110167924A (https=) |
| AU (2) | AU2017348322B8 (https=) |
| CA (1) | CA3041840A1 (https=) |
| EA (1) | EA201991071A1 (https=) |
| IL (1) | IL266053A (https=) |
| MX (1) | MX2019004950A (https=) |
| SG (2) | SG10202104386UA (https=) |
| WO (1) | WO2018081530A1 (https=) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102667413B1 (ko) * | 2016-10-27 | 2024-05-21 | 삼성전자주식회사 | 음성 명령에 기초하여 애플리케이션을 실행하는 방법 및 장치 |
| EP3532464A4 (en) | 2016-10-28 | 2020-07-08 | Icahn School of Medicine at Mount Sinai | COMPOSITIONS AND METHODS FOR THE TREATMENT OF EZH2 MEDIATION CANCER |
| JP2020514252A (ja) | 2016-12-08 | 2020-05-21 | アイカーン スクール オブ メディスン アット マウント シナイ | Cdk4/6媒介性がんを治療するための組成物および方法 |
| US11191741B2 (en) | 2016-12-24 | 2021-12-07 | Arvinas Operations, Inc. | Compounds and methods for the targeted degradation of enhancer of zeste homolog 2 polypeptide |
| CA3092677A1 (en) | 2018-03-06 | 2019-09-12 | Icahn School Of Medicine At Mount Sinai | Serine threonine kinase (akt) degradation / disruption compounds and methods of use |
| CN118344338A (zh) | 2018-04-23 | 2024-07-16 | 细胞基因公司 | 取代的4-氨基异吲哚啉-1,3-二酮化合物以及它们用于治疗淋巴瘤的用途 |
| CA3104298A1 (en) | 2018-06-21 | 2019-12-26 | Icahn School Of Medicine At Mount Sinai | Wd40 repeat domain protein 5 (wdr5) degradation / disruption compounds and methods of use |
| JP7712867B2 (ja) * | 2018-11-02 | 2025-07-24 | ダナ-ファーバー キャンサー インスティテュート,インコーポレイテッド | アセチル化ライター阻害剤の開発およびその使用 |
| CN118908962A (zh) | 2019-05-06 | 2024-11-08 | 西奈山伊坎医学院 | 作为hpk1的降解剂的异双功能化合物 |
| CN112457365B (zh) * | 2019-09-09 | 2023-06-09 | 中国医学科学院药物研究所 | 一类靶向蛋白质水解通路的功能分子及其制备和应用 |
| DK4034535T3 (da) | 2019-09-26 | 2026-04-07 | Novartis Ag | Aza-quinolinforbindelser og anvendelser deraf |
| CN110862434B (zh) * | 2019-10-28 | 2021-07-06 | 中山大学 | 一种可促进TGF-β1蛋白靶向降解的化合物及其制备方法与应用 |
| KR102505664B1 (ko) * | 2019-10-31 | 2023-03-03 | 재단법인 대구경북첨단의료산업진흥재단 | Ezh2 저해제 및 e3 리가제 바인더를 포함하는 화합물 및 이를 유효성분으로 함유하는 ezh2 관련 질환의 예방 또는 치료용 약학적 조성물 |
| WO2023205701A1 (en) | 2022-04-20 | 2023-10-26 | Kumquat Biosciences Inc. | Macrocyclic heterocycles and uses thereof |
| CN111303133A (zh) * | 2020-03-25 | 2020-06-19 | 清华大学 | 降解ezh2蛋白的小分子化合物 |
| CN112920176B (zh) * | 2020-05-25 | 2022-11-04 | 四川大学华西医院 | 可诱导prc2蛋白复合物核心亚基降解的双功能化合物和药物组合物及应用 |
| US12103924B2 (en) | 2020-06-01 | 2024-10-01 | Icahn School Of Medicine At Mount Sinai | Mitogen-activated protein kinase kinase (MEK) degradation compounds and methods of use |
| MX2023001603A (es) * | 2020-08-13 | 2023-03-07 | Hanmi Pharmaceutical Co Ltd | Derivados de dioxoloisoquinolinona novedosos y uso de los mismos. |
| CN113214203A (zh) * | 2020-12-16 | 2021-08-06 | 中山大学肿瘤防治中心(中山大学附属肿瘤医院、中山大学肿瘤研究所) | 基于ezh2蛋白降解的小分子化合物及其应用 |
| WO2022159650A1 (en) * | 2021-01-22 | 2022-07-28 | Icahn School Of Medicine At Mount Sinai | HETEROBIFUNCTIONAL COMPOUNDS AS DEGRADERS OF eEF1A2 |
| US12042543B2 (en) * | 2021-04-30 | 2024-07-23 | Northwestern University | Substituted 3-amino-5-phenylbenzamide compounds as covalent inhibitors of enhancer zeste homolog 2 (EZH2) and proteolysis-targeting chimeric derivatives thereof (PROTACs) that induce degradation of EZH2 |
| CN120981456A (zh) | 2023-05-24 | 2025-11-18 | 金橘生物科技公司 | 杂环化合物及其用途 |
| AU2024307234A1 (en) | 2023-06-30 | 2026-01-29 | Kumquat Biosciences Inc. | Substituted condensed tricyclic amine compounds and uses thereof as ras inhibitors |
| WO2025096855A1 (en) | 2023-11-02 | 2025-05-08 | Kumquat Biosciences Inc. | Degraders and uses thereof |
| KR20250088371A (ko) * | 2023-12-08 | 2025-06-17 | 인제대학교 산학협력단 | Ezh2 저해제 및 jak3 억제제를 포함하는 암의 예방 또는 치료용 약학적 조성물 |
| KR20250088374A (ko) * | 2023-12-08 | 2025-06-17 | 인제대학교 산학협력단 | Ezh2 저해제 및 mettl3 억제제를 포함하는 암의 예방 또는 치료용 약제학적 조성물 |
| CN118420604A (zh) * | 2024-03-29 | 2024-08-02 | 中国药科大学 | 一种以降冰片烯为疏水基团修饰的ezh2蛋白降解剂及其制备方法和应用 |
Family Cites Families (78)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5691147A (en) | 1994-06-02 | 1997-11-25 | Mitotix, Inc. | CDK4 binding assay |
| US6486214B1 (en) | 1997-09-10 | 2002-11-26 | Rutgers, The State University Of New Jersey | Polyanhydride linkers for production of drug polymers and drug polymer compositions produced thereby |
| SI1255752T1 (sl) | 2000-02-15 | 2007-12-31 | Pharmacia & Upjohn Co Llc | S pirolom substituirani zaviralci 2-indolinon protein kinaza |
| CA2546754A1 (en) | 2003-11-21 | 2005-06-09 | Array Biopharma Inc. | Akt protein kinase inhibitors |
| CA2590961C (en) | 2004-12-28 | 2013-11-26 | Exelixis, Inc. | [1h-pyrazolo[3,4-d]pyrimidin-4-yl]-piperidine or -piperazine compounds as serine-threonine kinase modulators (p70s6k, atk1 and atk2) for the treatment of immunological, inflammatory and proliferative diseases |
| UA95641C2 (xx) | 2006-07-06 | 2011-08-25 | Эррей Биофарма Инк. | Гідроксильовані піримідильні циклопентани як інгібітори акт протеїнкінази$гидроксилированные пиримидильные циклопентаны как ингибиторы акт протеинкиназы |
| EP2049500B1 (en) | 2006-07-06 | 2011-09-07 | Array Biopharma, Inc. | Cyclopenta [d] pyrimidines as akt protein kinase inhibitors |
| PL2076260T3 (pl) | 2006-09-15 | 2011-08-31 | Celgene Corp | Związki N-metyloaminometylo-izoindolu, kompozycje zawierające te związki, oraz metody ich stosowania |
| WO2008109104A1 (en) | 2007-03-07 | 2008-09-12 | The Regents Of The University Of California | Bivalent inhibitors of akt protein kinase |
| CN103396409B (zh) | 2007-07-05 | 2015-03-11 | 阵列生物制药公司 | 作为akt蛋白激酶抑制剂的嘧啶基环戊烷 |
| CN101918373B (zh) | 2007-07-05 | 2013-06-05 | 阵列生物制药公司 | 作为akt蛋白激酶抑制剂的嘧啶基环戊烷 |
| WO2009134418A2 (en) | 2008-04-30 | 2009-11-05 | Fox Chase Cancer Center | Assay for identifying agents that modulate epigenetic silencing, and agents identified thereby |
| EP2473054B1 (en) | 2009-09-04 | 2017-06-14 | The Regents of the University of Michigan | Compositions and methods for treatment of leukemia |
| EP2536706B1 (en) | 2010-02-11 | 2017-06-14 | Celgene Corporation | Arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same |
| CN103189067A (zh) | 2010-06-16 | 2013-07-03 | 密执安大学评议会 | Wdr5与其结合配偶体的相互作用的抑制及治疗方法 |
| WO2012078492A1 (en) | 2010-12-06 | 2012-06-14 | Celgene Corporation | A combination therapy with lenalidomide and a cdk inhibitor for treating multiple myeloma |
| CA2861066C (en) | 2012-01-12 | 2024-01-02 | Yale University | Compounds and methods for the enhanced degradation of targeted proteins and other polypeptides by an e3 ubiquitin ligase |
| US20150119435A1 (en) | 2012-05-11 | 2015-04-30 | Yale University | Compounds useful for promoting protein degradation and methods using same |
| US9758522B2 (en) | 2012-10-19 | 2017-09-12 | Dana-Farber Cancer Institute, Inc. | Hydrophobically tagged small molecules as inducers of protein degradation |
| UA118548C2 (uk) | 2012-12-21 | 2019-02-11 | Епізайм, Інк. | Тетрагідро- та дигідроізохіноліни як інгібітори prmt5 та їх застосування |
| US20170305857A1 (en) | 2013-12-20 | 2017-10-26 | Pfizer Limited | N-acylpiperidine ether tropomyosin-related kinase inhibitors |
| US9796701B2 (en) | 2013-12-31 | 2017-10-24 | Xuanzhu Pharma Co., Ltd. | Kinase inhibitor and use thereof |
| WO2015104677A1 (en) * | 2014-01-10 | 2015-07-16 | Piramal Enterprises Limited | Heterocyclic compounds as ezh2 inhibitors |
| AU2015247817C1 (en) | 2014-04-14 | 2022-02-10 | Arvinas Operations, Inc. | Imide-based modulators of proteolysis and associated methods of use |
| JP6744826B2 (ja) | 2014-06-13 | 2020-08-19 | バック バイオサイエンシーズ, エルエルシーBach BioSciences, LLC | Fap活性化治療剤及びそれに関連する使用 |
| EP3177288A4 (en) | 2014-08-04 | 2018-04-04 | Epizyme, Inc. | Prmt5 inhibitors and uses thereof |
| EP3885343A1 (en) * | 2014-11-06 | 2021-09-29 | Dana-Farber Cancer Institute, Inc. | Indole compounds as ezh2 inhibitors and uses thereof |
| EP3227446A1 (en) | 2014-12-01 | 2017-10-11 | Novartis AG | Compositions and methods for diagnosis and treatment of prostate cancer |
| JP6815318B2 (ja) | 2014-12-23 | 2021-01-20 | ダナ−ファーバー キャンサー インスティテュート,インコーポレイテッド | 二官能性分子によって標的化タンパク質分解を誘導する方法 |
| WO2016106518A1 (zh) * | 2014-12-29 | 2016-07-07 | 深圳市日上光电股份有限公司 | 导线集成式照明灯箱 |
| AR103297A1 (es) | 2014-12-30 | 2017-05-03 | Forma Therapeutics Inc | Pirrolo y pirazolopirimidinas como inhibidores de la proteasa 7 específica de ubiquitina |
| WO2016115480A1 (en) | 2015-01-16 | 2016-07-21 | Vedantra Pharmaceuticals, Inc. | Multilamellar lipid vesicle compositions including a conjugated anaplastic lymphoma kinase (alk) variant and uses thereof |
| US10730870B2 (en) * | 2015-03-18 | 2020-08-04 | Arvinas Operations, Inc. | Compounds and methods for the enhanced degradation of targeted proteins |
| US10364247B2 (en) | 2015-04-21 | 2019-07-30 | Ruijin Hospital Affiliated To Shanghai Jiao Tong University School Of Medicine | Preparation and use of novel protein kinase inhibitors |
| EP3289074B1 (en) | 2015-04-28 | 2023-10-04 | Université de Strasbourg | Clinical gene signature-based human cell culture model and uses thereof |
| HUE054149T2 (hu) | 2015-06-04 | 2021-08-30 | Arvinas Operations Inc | Proteolízis imid-alapú modulátorai és ezekkel kapcsolatos felhasználási eljárások |
| RU2719477C2 (ru) | 2015-06-22 | 2020-04-17 | Оно Фармасьютикал Ко., Лтд. | Соединение, ингибирующее brk |
| CN105085620B (zh) | 2015-06-25 | 2018-05-08 | 中山大学附属第一医院 | 一种靶向泛素化降解Smad3的化合物 |
| WO2017007612A1 (en) | 2015-07-07 | 2017-01-12 | Dana-Farber Cancer Institute, Inc. | Methods to induce targeted protein degradation through bifunctional molecules |
| WO2017011371A1 (en) * | 2015-07-10 | 2017-01-19 | Arvinas, Inc | Mdm2-based modulators of proteolysis and associated methods of use |
| CA2988436A1 (en) * | 2015-07-13 | 2017-01-19 | Arvinas, Inc. | Alanine-based modulators of proteolysis and associated methods of use |
| CN105175284B (zh) | 2015-07-21 | 2017-06-16 | 中国药科大学 | 酰胺类化合物、制备方法及其医药用途 |
| WO2017024318A1 (en) | 2015-08-06 | 2017-02-09 | Dana-Farber Cancer Institute, Inc. | Targeted protein degradation to attenuate adoptive t-cell therapy associated adverse inflammatory responses |
| WO2017024317A2 (en) | 2015-08-06 | 2017-02-09 | Dana-Farber Cancer Institute, Inc. | Methods to induce targeted protein degradation through bifunctional molecules |
| US9809603B1 (en) | 2015-08-18 | 2017-11-07 | Deuterx, Llc | Deuterium-enriched isoindolinonyl-piperidinonyl conjugates and oxoquinazolin-3(4H)-yl-piperidinonyl conjugates and methods of treating medical disorders using same |
| WO2017040990A1 (en) | 2015-09-03 | 2017-03-09 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof |
| AU2016349781A1 (en) | 2015-11-02 | 2018-05-10 | Yale University | Proteolysis targeting chimera compounds and methods of preparing and using same |
| CA3015417A1 (en) | 2016-03-01 | 2017-09-08 | Propellon Therapeutics Inc. | Inhibitors of wdr5 protein-protein binding |
| JP7624690B2 (ja) | 2016-03-01 | 2025-01-31 | プロペロン セラピューティクス インコーポレイテッド | Wdr5タンパク質-タンパク質結合の阻害剤 |
| WO2017185031A1 (en) * | 2016-04-22 | 2017-10-26 | Dana-Farber Cancer Institute, Inc. | Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use |
| CN109790143A (zh) | 2016-05-10 | 2019-05-21 | C4医药公司 | 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体 |
| EP4491236A3 (en) | 2016-05-10 | 2025-04-02 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
| TW201811799A (zh) | 2016-09-09 | 2018-04-01 | 美商英塞特公司 | 吡唑并嘧啶化合物及其用途 |
| UA125650C2 (uk) | 2016-09-09 | 2022-05-11 | Інсайт Корпорейшн | Регулятори нрk1 на основі похідних піразолопіридину та їх застосування для лікування раку |
| US10160763B2 (en) | 2016-09-13 | 2018-12-25 | Vanderbilt University | WDR5 inhibitors and modulators |
| EP3532464A4 (en) | 2016-10-28 | 2020-07-08 | Icahn School of Medicine at Mount Sinai | COMPOSITIONS AND METHODS FOR THE TREATMENT OF EZH2 MEDIATION CANCER |
| CA3042301A1 (en) | 2016-11-22 | 2018-05-31 | Dana-Farber Cancer Institute, Inc. | Degradation of protein kinases by conjugation of protein kinase inhibitors with e3 ligase ligand and methods of use |
| JP2020514252A (ja) | 2016-12-08 | 2020-05-21 | アイカーン スクール オブ メディスン アット マウント シナイ | Cdk4/6媒介性がんを治療するための組成物および方法 |
| US11052091B2 (en) | 2016-12-21 | 2021-07-06 | Ono Pharmaceutical Co., Ltd. | BRK inhibitory compound |
| MX2019007646A (es) | 2016-12-23 | 2019-09-06 | Arvinas Operations Inc | Moleculas quimericas dirigidas a la proteolisis del egfr y metodos asociados de uso. |
| BR112019015484A2 (pt) | 2017-01-31 | 2020-04-28 | Arvinas Operations Inc | ligantes de cereblon e compostos bifuncionais compreendendo os mesmos |
| WO2019084030A1 (en) | 2017-10-24 | 2019-05-02 | Genentech, Inc. | (4-HYDROXYPYRROLIDIN-2-YL) -HYDROXAMATE COMPOUNDS AND METHODS OF USE |
| WO2019113071A1 (en) | 2017-12-05 | 2019-06-13 | Icahn School Of Medicine At Mount Sinai | Compositions and methods for treating alk-mediated cancer |
| EP3743069B1 (en) | 2018-01-22 | 2025-08-06 | BioVentures, LLC | Bcl-2 proteins degraders for cancer treatment |
| WO2019165189A1 (en) | 2018-02-22 | 2019-08-29 | Icahn School Of Medicine At Mount Sinai | Protein arginine methyltransferase 5 (prmt5) degradation / disruption compounds and methods of use |
| CA3092677A1 (en) | 2018-03-06 | 2019-09-12 | Icahn School Of Medicine At Mount Sinai | Serine threonine kinase (akt) degradation / disruption compounds and methods of use |
| JP7421499B2 (ja) | 2018-05-15 | 2024-01-24 | アメリカ合衆国 | 腫瘍転移および腫瘍発生の予防および治療のための製剤および方法 |
| CA3104298A1 (en) | 2018-06-21 | 2019-12-26 | Icahn School Of Medicine At Mount Sinai | Wd40 repeat domain protein 5 (wdr5) degradation / disruption compounds and methods of use |
| EP3817745A4 (en) | 2018-07-05 | 2022-04-06 | Icahn School of Medicine at Mount Sinai | PROTEIN TYROSINE KINASE 6 (PTK6) DEGRADATION/DISPUTED COMPOUNDS AND METHODS OF USE |
| CN118908962A (zh) | 2019-05-06 | 2024-11-08 | 西奈山伊坎医学院 | 作为hpk1的降解剂的异双功能化合物 |
| CN114269749B (zh) | 2019-06-10 | 2024-10-01 | 苏特罗生物制药公司 | 5H-吡咯并[3,2-d]嘧啶-2,4-二氨基化合物及其抗体偶联物 |
| WO2021021904A1 (en) | 2019-07-30 | 2021-02-04 | The Scripps Research Institute | Pharmacological inhibitors of the enl yeats domain |
| CN112552293A (zh) | 2019-09-25 | 2021-03-26 | 珠海宇繁生物科技有限责任公司 | 一种protac小分子化合物及其应用 |
| US11739101B2 (en) | 2020-05-06 | 2023-08-29 | Nurix Therapeutics, Inc. | Bifunctional degraders of hematopoietic progenitor kinase and therapeutic uses thereof |
| US12103924B2 (en) | 2020-06-01 | 2024-10-01 | Icahn School Of Medicine At Mount Sinai | Mitogen-activated protein kinase kinase (MEK) degradation compounds and methods of use |
| WO2022086937A1 (en) | 2020-10-21 | 2022-04-28 | Icahn School Of Medicine At Mount Sinai | Heterobifunctional compounds as degraders of enl |
| CN112778303A (zh) | 2020-12-31 | 2021-05-11 | 武汉九州钰民医药科技有限公司 | Cdk4/6激酶抑制剂shr6390的制备方法 |
| WO2023006063A1 (en) | 2021-07-30 | 2023-02-02 | Beigene, Ltd. | PYRROLO [2, 3-b] PYRAZINE-BASED BIFUNCTIONAL COMPOUNDS AS HPK1 DEGRADERS AND THE USE THEREOF |
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2017
- 2017-10-27 EP EP17863645.2A patent/EP3532464A4/en not_active Withdrawn
- 2017-10-27 SG SG10202104386UA patent/SG10202104386UA/en unknown
- 2017-10-27 SG SG11201903483VA patent/SG11201903483VA/en unknown
- 2017-10-27 US US16/345,591 patent/US20190255041A1/en not_active Abandoned
- 2017-10-27 JP JP2019522841A patent/JP2019537585A/ja active Pending
- 2017-10-27 CA CA3041840A patent/CA3041840A1/en not_active Abandoned
- 2017-10-27 EA EA201991071A patent/EA201991071A1/ru unknown
- 2017-10-27 KR KR1020197015152A patent/KR20190084063A/ko not_active Withdrawn
- 2017-10-27 WO PCT/US2017/058718 patent/WO2018081530A1/en not_active Ceased
- 2017-10-27 AU AU2017348322A patent/AU2017348322B8/en not_active Ceased
- 2017-10-27 CN CN201780081246.8A patent/CN110167924A/zh active Pending
- 2017-10-27 MX MX2019004950A patent/MX2019004950A/es unknown
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2019
- 2019-04-15 IL IL266053A patent/IL266053A/en unknown
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2020
- 2020-07-10 US US16/926,418 patent/US11510920B2/en active Active
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2022
- 2022-03-03 AU AU2022201488A patent/AU2022201488A1/en not_active Abandoned
- 2022-11-01 US US17/978,696 patent/US12274697B2/en active Active
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