公开(公告)号：US20240140999A1

公开(公告)日：2024-05-02

申请号：US18113539

申请日：2023-02-23

申请人： Dana-Farber Cancer Institute, Inc.

发明人： Loren D. Walensky ,  Gregory H. Bird ,  Ann Morgan Cathcart ,  Rida Mourtada ,  Henry D. Herce ,  James E. Bradner

IPC分类号： C07K14/435 ,  A61K47/54

CPC分类号： C07K14/435 ,  A61K47/545 ,  C07K2319/00

摘要： The present application describes stapled peptide degron chimeras, which act as protein degradation inducing moieties, either by combining a stapled peptide that binds a disease-related protein with a small molecule degron, such as a cereblon- or VHL-binding small molecule as the degron, or a polypeptide sequence degron, such as a Cop1-binding Trib peptide as the degron; or by combining a stapled peptide degron with a peptide, such as a stapled peptide, or a small molecule that binds a disease-related protein. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of stapled peptide degron chimeras which can be utilized in the treatment of proliferative disorders or other conditions whereby elimination of a disease-causing or disease-related protein would have a therapeutic benefit. The present application also provides methods for making compounds of the application and intermediates thereof.

公开(公告)号：US20220169688A1

公开(公告)日：2022-06-02

申请号：US17600468

申请日：2020-04-17

申请人： Dana-Farber Cancer Institute, Inc.

发明人： Loren D. Walensky ,  Ann Morgan Cathcart ,  Gregory H. Bird

IPC分类号： C07K14/47

摘要： This disclosure features structurally-stabilized and/or warhead-bearing structurally stabilized peptide inhibitors for targeting ubiquitin activating enzymes (E1). Also disclosed are methods of using such structurally-stabilized and warhead-bearing structurally stabilized peptides in the treatment of E1-expressing or -dependent cancers or diseases. Also provided are combination therapies N comprising such structurally-stabilized and/or warhead-bearing structurally stabilized peptide for the treatment of E1-expressing or -dependent diseases.

公开(公告)号：US20240075099A1

公开(公告)日：2024-03-07

申请号：US18315725

申请日：2023-05-11

申请人： Dana-Farber Cancer Institute, Inc.

发明人： Loren D. Walensky ,  Kimberly Stegmaier ,  Ann Morgan Cathcart ,  Björn Stolte

IPC分类号： A61K38/17 ,  A61K31/496 ,  A61K45/06 ,  A61P35/02 ,  C07K4/12 ,  C07K14/47 ,  G01N33/574

CPC分类号： A61K38/1758 ,  A61K31/496 ,  A61K45/06 ,  A61P35/02 ,  C07K4/12 ,  C07K14/47 ,  C07K14/4746 ,  G01N33/574 ,  G01N33/57426 ,  G01N2800/52

摘要： Methods for assessing the efficacy of internally cross-linked p53 transactivation domain-based inhibitor peptides in the treatment of pediatric cancer and methods of using such peptides to treat pediatric cancer are provided.