公开(公告)号：WO2022087433A8

公开(公告)日：2022-04-28

申请号：PCT/US2021/056280

申请日：2021-10-22

申请人： DANA-FARBER CANCER INSTITUTE, INC. ,  GRAY, Nathanael, S. ,  CHOUCHANI, Edward ,  ZHANG, Tinghu ,  DARABEDIAN, Narek ,  JI, Wenzhi ,  CHE, Jianwei

发明人： GRAY, Nathanael, S. ,  CHOUCHANI, Edward ,  ZHANG, Tinghu ,  DARABEDIAN, Narek ,  JI, Wenzhi ,  CHE, Jianwei

IPC分类号： A61P35/00 ,  C07D265/36 ,  C07D413/04 ,  A61K31/538

摘要： The present disclosure relates to compounds of formula I that are capable of inhibiting creatine kinase. The present disclosure also relates to methods of treating cancer, such as hematological malignancies.

公开(公告)号：WO2021173677A1

公开(公告)日：2021-09-02

申请号：PCT/US2021/019424

申请日：2021-02-24

申请人： DANA-FARBER CANCER INSTITUTE, INC. ,  HATCHER, John M. ,  GRAY, Nathanael S. ,  JIANG, Baishan ,  ZHANG, Tinghu ,  CHE, Jianwei ,  GAO, Yang ,  JONES, Lyn Howard

发明人： HATCHER, John M. ,  GRAY, Nathanael S. ,  JIANG, Baishan ,  ZHANG, Tinghu ,  CHE, Jianwei ,  GAO, Yang ,  JONES, Lyn Howard

IPC分类号： A61K31/505 ,  A61K31/506 ,  A61K31/445 ,  A61K47/55 ,  A61P35/00 ,  A61K31/5025 ,  C07D487/04

摘要： Disclosed are bispecific compounds (degraders) that target ALK or ALK and FAK for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the bispecific compounds to treat diseases and disorders characterized or mediated by aberrant ALK or ALK and FAK activity.

公开(公告)号：WO2022081478A1

公开(公告)日：2022-04-21

申请号：PCT/US2021/054419

申请日：2021-10-11

申请人： DANA-FARBER CANCER INSTITUTE, INC. ,  GRAY, Nathanael S. ,  LI, Zhengnian ,  CHE, Jianwei ,  ZHANG, Tinghu

发明人： GRAY, Nathanael S. ,  LI, Zhengnian ,  CHE, Jianwei ,  ZHANG, Tinghu

IPC分类号： A61K31/435 ,  A61K31/517 ,  A61K31/5377

摘要： The disclosure relates to compounds that act as covalent inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.

公开(公告)号：WO2022197993A1

公开(公告)日：2022-09-22

申请号：PCT/US2022/020857

申请日：2022-03-18

申请人： DANA-FARBER CANCER INSTITUTE, INC. ,  YEDA RESEARCH AND DEVELOPMENT CO. LTD. ,  YOU, Inchul ,  GRAY, Nathanael S. ,  ZHANG, Tinghu ,  DHE-PAGANON, Sirano ,  LONDON, Nir ,  DUBIELLA, Christian

发明人： YOU, Inchul ,  GRAY, Nathanael S. ,  ZHANG, Tinghu ,  DHE-PAGANON, Sirano ,  LONDON, Nir ,  DUBIELLA, Christian

IPC分类号： A61K31/381 ,  A61K45/06 ,  A61P35/00 ,  C07D333/48

摘要： Disclosed are compounds which inhibit Pin1 activity, methods of making the compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat diseases or disorders characterized or mediated by dysregulated Pin1 activity.

公开(公告)号：WO2022140554A1

公开(公告)日：2022-06-30

申请号：PCT/US2021/064880

申请日：2021-12-22

申请人： DANA-FARBER CANCER INSTITUTE, INC. ,  CORNELL UNIVERSITY ,  GRAY, Nathanael S. ,  ZHANG, Tinghu ,  CANTLEY, Lewis C. ,  SIVAKUMAREN, Carmen ,  MANZ, Theresa ,  WANG, Eric ,  JI, Wenzhi ,  FISCHER, Eric S. ,  DONOVAN, Katherine

发明人： GRAY, Nathanael S. ,  ZHANG, Tinghu ,  CANTLEY, Lewis C. ,  SIVAKUMAREN, Carmen ,  MANZ, Theresa ,  WANG, Eric ,  JI, Wenzhi ,  FISCHER, Eric S. ,  DONOVAN, Katherine

IPC分类号： A61K31/495 ,  A61K31/4965 ,  A61K31/497 ,  C07D239/42 ,  C07D403/02 ,  C07D403/04

摘要： The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions by modulating (e.g., reducing) the level or activity of at least one of PIP4K2A, PIP4K2B, and PIP4K2C.

公开(公告)号：WO2020257385A1

公开(公告)日：2020-12-24

申请号：PCT/US2020/038325

申请日：2020-06-18

申请人： DANA-FARBER CANCER INSTITUTE, INC. ,  GRAY, Nathanael, S. ,  DU, Guangyan ,  ZHANG, Tinghu ,  WESTOVER, Kenneth ,  GURBANI, Deepak

发明人： GRAY, Nathanael, S. ,  DU, Guangyan ,  ZHANG, Tinghu ,  WESTOVER, Kenneth ,  GURBANI, Deepak ,  HENNING, Nathaniel ,  RAO, Suman

IPC分类号： A61K31/519 ,  A61K31/5377 ,  A61K31/541

摘要： Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof. Also disclosed herein are methods of using the compounds of Formula (I) in the treatment of certain diseases (e.g., cancer).

公开(公告)号：WO2021257660A1

公开(公告)日：2021-12-23

申请号：PCT/US2021/037566

申请日：2021-06-16

申请人： DANA-FARBER CANCER INSTITUTE, INC. ,  GRAY, Nathanael, S. ,  FAN, Mengyang ,  ORDONEZ, Martha ,  CHOUCHANI, Edward ,  ZHANG, Tinghu ,  LI, Zhengnian ,  CHE, Jianwei

发明人： GRAY, Nathanael, S. ,  FAN, Mengyang ,  ORDONEZ, Martha ,  CHOUCHANI, Edward ,  ZHANG, Tinghu ,  LI, Zhengnian ,  CHE, Jianwei

IPC分类号： A61K31/713 ,  C12N15/113

摘要： Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof. The compounds of Formula (I) are useful for activating uncoupling protein 1 (UCP1) dependent thermogenesis. Also disclosed herein are methods of treating obesity or metabolic disorders such as diabetes using a compound of Formula (I).

公开(公告)号：WO2015058126A1

公开(公告)日：2015-04-23

申请号：PCT/US2014/061206

申请日：2014-10-17

申请人： SYROS PHARMACEUTICALS, INC. ,  DANA-FARBER CANCER INSTITUTE, INC. ,  PARAZA PHARMA, INC. ,  CIBLAT, Stephane ,  DEROY, Patrick ,  GRAY, Nathanael ,  LEBLANC, Melissa ,  MARINEAU, Jason, J. ,  MOORE, Joel ,  SPROTT, Kevin ,  ZHANG, Tinghu ,  SIDIQUI, M., Arshad ,  KABRO, Anzhelika ,  LEGER, Serge ,  MILLER, Tom ,  ROY, Stephanie ,  SCHMIDT, Darby ,  WINTER, Dana, K. ,  BRADLEY, Michael

发明人： CIBLAT, Stephane ,  DEROY, Patrick ,  GRAY, Nathanael ,  LEBLANC, Melissa ,  MARINEAU, Jason, J. ,  MOORE, Joel ,  SPROTT, Kevin ,  ZHANG, Tinghu ,  SIDIQUI, M., Arshad ,  KABRO, Anzhelika ,  LEGER, Serge ,  MILLER, Tom ,  ROY, Stephanie ,  SCHMIDT, Darby ,  WINTER, Dana, K. ,  BRADLEY, Michael

IPC分类号： C07D401/14 ,  A61K31/506 ,  A61P35/02

CPC分类号： C07D401/14 ,  A61K31/506 ,  A61K45/06

摘要： The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

摘要翻译： 本发明提供新的式（I）化合物及其药学上可接受的盐，溶剂合物，水合物，互变异构体，立体异构体，同位素标记的衍生物及其组合物。 还提供了涉及用于治疗或预防受试者的增殖性疾病（例如，癌症（例如白血病，黑素瘤，多发性骨髓瘤），良性肿瘤，血管生成，炎性疾病，自身炎性疾病和自身免疫性疾病）的化合物或组合物的方法和试剂盒 。 使用本发明的化合物或组合物治疗具有增殖性疾病的受试者可以抑制激酶例如细胞周期蛋白依赖性激酶（CDK）（例如细胞周期蛋白依赖性激酶7（CDK7））的异常活性，因此 ，诱导受试者的细胞凋亡和/或抑制转录。

公开(公告)号：WO2010044924A1

公开(公告)日：2010-04-22

申请号：PCT/US2009/047854

申请日：2009-06-18

申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  LEE, Benhur ,  JUNG, Michael, E. ,  WOLF, Michael, C. ,  ZHANG, Tinghu

发明人： LEE, Benhur ,  JUNG, Michael, E. ,  WOLF, Michael, C. ,  ZHANG, Tinghu

IPC分类号： A61K31/381 ,  A61K31/00

CPC分类号： A61K31/00 ,  A61K31/381 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/393 ,  Y02A50/397

摘要： Provided herein are a series of arylmethylidene rhodanine derivatives having broad- spectrum antiviral activity against enveloped viruses, including but not limited to fϊloviruses, poxviruses, arenaviruses, bunyaviruses, paramyxoviruses, flaviviruses, influenza A, and HIV- 1. The compounds act via a novel mechanism to disrupt viral membranes and inhibit viral attachment, fusion, and/or entry into host cells. The membrane disrupting activity of the compounds is selective for viral membranes relative to other biological membranes, making the compounds non-toxic to cells and host subjects.

摘要翻译： 本文提供了一系列具有针对包膜病毒的广谱抗病毒活性的芳基亚甲基绕丹宁衍生物，其包括但不限于环状病毒，痘病毒，氨基葡萄病毒，布尼瓦病毒，副粘病毒，黄病毒，甲型流感和HIV-1。 一种破坏病毒膜并抑制病毒附着，融合和/或进入宿主细胞的新机制。 化合物的膜破坏活性相对于其他生物膜对病毒膜是选择性的，使得化合物对细胞和宿主受试者无毒。

公开(公告)号：WO2022232088A1

公开(公告)日：2022-11-03

申请号：PCT/US2022/026268

申请日：2022-04-26

申请人： DANA-FARBER CANCER INSTITUTE, INC. ,  GRAY, Nathanael, S. ,  ZHANG, Tinghu ,  FAN, Mengyang ,  CHE, Jianwei ,  LU, Wenchao ,  DHE-PAGANON, Sirano ,  KWIATKOWSKI, Nicholas, Paul

发明人： GRAY, Nathanael, S. ,  ZHANG, Tinghu ,  FAN, Mengyang ,  CHE, Jianwei ,  LU, Wenchao ,  DHE-PAGANON, Sirano ,  KWIATKOWSKI, Nicholas, Paul

IPC分类号： C07D403/12 ,  C07D207/14 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D413/12 ,  A61P35/00 ,  A61K31/506

摘要： Provided herein are compounds of Formula (I'), Formula (II), Formula (III), Formula (IV), Formula (V), Formula (VI), Formula (VII), or Formula (VIII) and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, or prodrugs thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing diseases (e.g., proliferative diseases (e.g., cancers, such as carcinoma, sarcoma, lung cancer, thyroid cancer, skin cancer, ovarian cancer, colorectal cancer, prostate cancer, pancreatic cancer, esophageal cancer, liver cancer, breast cancer)) in a subject. Provided are methods of inhibiting a TEAD transcription factors (e.g., TEAD1, TEAD2, TEAD3, TEAD4) in a subject.