Patents by Inventor Tinghu Zhang

Tinghu Zhang has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 11505560
    Abstract: Disclosed are heterobifunctional compounds that effectuate selective degradation of a target protein, and which include a targeting ligand that binds a target protein and at least one other protein, a ligand that binds an E3 ubiquitin ligase or a component of E3 ubiquitin ligase, and a specificity modulating linker that links the first ligand and the second ligand. Pharmaceutical compositions containing the compounds, and methods of using and making the compounds are also disclosed.
    Type: Grant
    Filed: October 19, 2018
    Date of Patent: November 22, 2022
    Assignee: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Radoslaw P. Nowak, Eric S. Fischer, Nathanael S. Gray, Tinghu Zhang, Zhixiang He, Brian Groendyke
  • Publication number: 20220281874
    Abstract: The present disclosure provides compounds of Formula (I), (II-1), (II-2), (II-3), or (II-4). The compounds of the present disclosure may be inhibitors of kinases (e.g., a cyclin-dependent kinase (CDK) (e.g., CDK7)). In some embodiments, the compounds disclosed herein are selective for inhibiting the activity of a kinase (e.g., CDK7) over certain other kinases (e.g., CDK2, CDK9, CDK12). In certain embodiments, the compounds do not bind or inhibit a 5-hydroxytryptamine (5-HT) receptor. Also provided are pharmaceutical compositions, kits, methods of use, and uses that involve the compounds disclosed herein. In some embodiments, the compounds are useful in inhibiting the activity of a kinase, inhibiting the growth of a cell, inducing apoptosis of a cell, treating a disease, and/or preventing a disease (e.g., proliferative disease, cystic fibrosis).
    Type: Application
    Filed: July 22, 2020
    Publication date: September 8, 2022
    Applicant: Dana-Farber Cancer Institure, Inc.
    Inventors: Tinghu Zhang, Nicholas Paul Kwiatkowski, Nathanael S. Gray, Zhixiang He, Yanke Liang
  • Publication number: 20220280649
    Abstract: Disclosed are bispecific compounds (degraders) that target CDK7 for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.
    Type: Application
    Filed: August 4, 2020
    Publication date: September 8, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Guangyan Du, Tinghu Zhang, Zhixiang He, Nicholas Kwiatkowski, Jie Jiang
  • Publication number: 20220267294
    Abstract: 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).
    Type: Application
    Filed: June 18, 2020
    Publication date: August 25, 2022
    Inventors: Nathanael S. Gray, Guangyan Du, Tinghu Zhang, Nathaniel Henning, Suman Rao, Kenneth Westover, Deepak Gurbani
  • Publication number: 20220242865
    Abstract: The present invention provides novel compounds of Formula (I), (II), or (III), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with 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.
    Type: Application
    Filed: April 7, 2022
    Publication date: August 4, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Nicholas Paul Kwiatkowski
  • Publication number: 20220226481
    Abstract: Disclosed are bifunctional compounds comprising a GDC-0068 analog that binds AKT isoforms AKT1, 2 and 3, pharmaceutical compositions, and methods for treating diseases or conditions mediated by dysfunctional AKT activity.
    Type: Application
    Filed: April 8, 2020
    Publication date: July 21, 2022
    Applicants: DANA-FARBER CANCER INSTITUTE, INC., BETH ISRAEL DEACONESS MEDICAL CENTER, INC.
    Inventors: Nathanael Gray, Inchul You, Tinghu Zhang, Eric Fischer, Katherine Donovan, Emily Erickson, Alex Toker
  • Publication number: 20220227734
    Abstract: Provided herein are bifunctional compounds with a moiety (e.g., lenalidomide, thalidomide) that is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and another moiety that is a binder of a target protein (e.g., kinase (e.g., CDK (e.g., CDK9 and/or CDK12))) to induce degradation of the target protein CDK9 and/or CDK12. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, such as cancers (e.g., ovarian cancer, breast cancer, or prostate cancer))). Provided also are methods of inducing the degradation of the target protein (e.g., kinase (e.g., CDK (e.g., CDK9 and/or CDK12))), and methods of inducing apoptosis in a cell in a biological sample or subject by administering the bifunctional compound or composition described herein.
    Type: Application
    Filed: April 23, 2020
    Publication date: July 21, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Jianwei Che, Nathanael S. Gray, Tinghu Zhang, Baishan Jiang, Yang Gao, Nicholas Paul Kwiatkowski
  • Publication number: 20220213067
    Abstract: The present invention provides novel compounds of Formulae (I?) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with 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.
    Type: Application
    Filed: March 7, 2022
    Publication date: July 7, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Baishan Jiang, Nicholas Paul Kwiatkowski
  • Publication number: 20220177466
    Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by Kelch-like ECH-associated protein 1 (KEAP1). In some aspects, the present invention is directed to methods of treating diseases or disorders involving dysfunctional (e.g., dysregulated) KEAP1 activity, that entails administration of a therapeutically effective amount of a bifunctional compound of formula I or a pharmaceutically acceptable salt or stereoisomer thereof, to a subject in need thereof.
    Type: Application
    Filed: April 7, 2020
    Publication date: June 9, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael Gray, Tinghu Zhang, Guangyan Du, Nathaniel Henning, Jie Jiang, Eric Fischer, Katherine Donovan
  • Publication number: 20220177443
    Abstract: Disclosed are compounds and pharmaceutically acceptable salts and stereoisomers thereof that may cause degradation of various proteins e.g., IKZF2 (Helios). Also disclosed are pharmaceutical compositions containing same, and methods of making and using the compounds to treat diseases and disorders characterized or mediated by aberrant protein activity.
    Type: Application
    Filed: December 3, 2019
    Publication date: June 9, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Alyssa Verano, Eric Wang, Radoslaw Nowak, Jing Ting Christine Yuan, Nathanael Gray, Eric Fischer, Tinghu Zhang, Hu Liu
  • Publication number: 20220175722
    Abstract: The present invention relates to bispecific compounds, compositions, and methods for treating diseases or conditions characterized or mediated by aberrant fibroblast growth factor receptor 2 (FGFR2) activity.
    Type: Application
    Filed: April 9, 2020
    Publication date: June 9, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael Gray, Tinghu Zhang, Guangyan Du, Nathaniel Henning, Jie Jiang
  • Publication number: 20220153730
    Abstract: The present invention provides novel compounds according to Formula (I): where Ring A, Ring B, X, L1, L2, RA, RC, RD, RE, m, n, and p are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of human diseases associated with kinase activity, for example, proliferative diseases, neurodegenerative diseases, metabolic disorders, inflammatory diseases, and cardiovascular diseases.
    Type: Application
    Filed: February 26, 2021
    Publication date: May 19, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang
  • Publication number: 20220153722
    Abstract: The present invention relates to bifunctional compounds, compositions, and methods for treating diseases or conditions mediated by dysfunctional cyclin-dependent kinase 2 (CDK2) and CDK5 activity.
    Type: Application
    Filed: April 2, 2020
    Publication date: May 19, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael Gray, Nicholas Kwiatkowski, Eric Fischer, Katherine Donovan, Tinghu Zhang, Mingxing Teng, Jie Jiang
  • Patent number: 11325910
    Abstract: The present invention provides novel compounds of Formula (I), (II), or (III), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with 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.
    Type: Grant
    Filed: February 3, 2020
    Date of Patent: May 10, 2022
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Nicholas Paul Kwiatkowski
  • Publication number: 20220127246
    Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).
    Type: Application
    Filed: November 7, 2019
    Publication date: April 28, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Yao Liu, David Weinstock, Loretta Sze-Mun Li
  • Publication number: 20220127284
    Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).
    Type: Application
    Filed: November 7, 2019
    Publication date: April 28, 2022
    Inventors: Nathanael S. Gray, Tinghu Zhang, Yao Liu Brookline, Mingfeng Flao, David Weinstock, Loretta Sze-Mun
  • Publication number: 20220127260
    Abstract: The present disclosure provides compounds of Formula (I?) (e.g., compounds of Formula (I)), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, cocrystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).
    Type: Application
    Filed: November 7, 2019
    Publication date: April 28, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Yao Liu, Zhixiang He, Mingfeng Hao, David Weinstock, Loretta Sze-Mun Li
  • Patent number: 11306070
    Abstract: The present invention provides novel compounds of Formulae (I?) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with 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.
    Type: Grant
    Filed: November 22, 2017
    Date of Patent: April 19, 2022
    Assignee: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Baishan Jiang, Nicholas Paul Kwiatkowski
  • Publication number: 20220112191
    Abstract: The present application provides bifunctional compounds of Formula (Ia) or (Ib): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 8 (CDK8). The present application also relates to methods for the targeted degradation of CDK8 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 which can be utilized in the treatment of disorders modulated by CDK8.
    Type: Application
    Filed: December 23, 2021
    Publication date: April 14, 2022
    Applicant: DANA-FARBER CANCER INSTITUTE, INC.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Calla M. Olson, Yanke Liang, Nicholas Kwiatkowski
  • Publication number: 20220089611
    Abstract: The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The compounds of the present disclosure are inhibitors of kinases (e.g., a cyclin-dependent kinase (CDK) (e.g., CDK7)). The compounds may be selective for inhibiting the activity of a kinase (e.g., CDK7) over certain other kinases (e.g., CDK2, CDK9, CDK12). Also provided are pharmaceutical compositions, kits, methods of use, and uses that involve the compounds. The compounds may be useful in inhibiting the activity of a kinase, down-regulating the transcription of MYC or MCL-1, inhibiting the growth of a cell, inducing apoptosis of a cell, treating a disease, and/or preventing a disease (e.g., proliferative disease, cystic fibrosis).
    Type: Application
    Filed: December 27, 2019
    Publication date: March 24, 2022
    Applicant: Dana-Farber Cancer Institute, Inc.
    Inventors: Nathanael S. Gray, Tinghu Zhang, Nicholas Paul Kwiatkowski, Jie Jiang, Mingfeng Hao, Zhixiang He