公开(公告)号：US20240132463A1

公开(公告)日：2024-04-25

申请号：US18368497

申请日：2023-09-14

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.

Inventor： Marcus FISHER ,  Fatemeh KERAMATNIA ,  Kevin MCGOWAN ,  Jaeki MIN ,  Gisele A. NISHIGUCHI ,  Jeanine PRICE ,  Zoran RANKOVIC ,  Sourav Das ,  Charles G. MULLIGHAN ,  Yunchao CHANG

IPC: C07D401/04 ,  A61K31/45 ,  A61K45/06 ,  A61P35/00 ,  A61P35/02 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

CPC classification number: C07D401/04 ,  A61K31/45 ,  A61K45/06 ,  A61P35/00 ,  A61P35/02 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

Abstract: In one aspect, the disclosure relates to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindolin-5-yl)arylsulfonamide analogs that useful as modulators of cereblon (CRBN) activity, methods of making same, pharmaceutical compositions comprising same, and methods of treating various clinical conditions and disorders using same, e.g., a disorder of uncontrolled cellular proliferation, such as a cancer, which may be associated with cereblon protein dysfunction and/or a GSPT1 dysfunction. In various further aspects, the disclosed compounds can selectively modulate the degradation of GSPT1 protein, i.e., the disclosed compounds can act as GSPT1 degraders. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

公开(公告)号：US20250122185A1

公开(公告)日：2025-04-17

申请号：US18712987

申请日：2022-11-23

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.

Inventor： Jun J. YANG ,  Zoran RANKOVIC ,  Jianzhong HU ,  Jamie JARUSIEWICZ ,  Gisele A. NISHIGUCHI

IPC: C07D417/14 ,  A61K31/506 ,  A61K31/55 ,  A61K45/06 ,  C07D471/08 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10

Abstract: In one aspect, the disclosure relates to proteolysis-targeting chimeric molecules (PROTACs) that induce degradation of LCK tyrosine kinase, i.e., the disclosed substituted N-(2-chloro-6-methylphenyl)-2-((6-(6-membered heterocycloalkyl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide analogues. The disclosed compounds are useful for modulating LCK tyrosine kinase activity through targeted degradation. In further aspects, the present disclosure relates to methods of making the disclosed compounds, pharmaceutical compositions comprising the disclosed compounds, and methods of treating various clinical conditions and disorders using same, e.g., a disorder of uncontrolled cellular proliferation, such as a cancer, which may be associated with a LCK tyrosine kinase dysfunction. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

公开(公告)号：US20220274948A1

公开(公告)日：2022-09-01

申请号：US17740148

申请日：2022-05-09

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.

Inventor： Marcus FISHER ,  Fatemeh KERAMATNIA ,  Kevin MCGOWAN ,  Jaeki MIN ,  Gisele A. NISHIGUCHI ,  Jeanine PRICE ,  Zoran RANKOVIC ,  Das SOURAV ,  Charles G. MULLIGHAN ,  Yunchao CHANG

IPC: C07D401/04 ,  A61K31/45 ,  A61K45/06 ,  C07D405/14 ,  C07D413/14 ,  C07D409/14 ,  A61P35/00 ,  A61P35/02

Abstract: In one aspect, the disclosure relates to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindolin-5-ypaiylsulfo namide analogs that useful as modulators of cereblon (CRBN) activity, methods of making same, pharmaceutical compositions comprising same, and methods of treating various clinical conditions and disorders using same, e.g., a disorder of uncontrolled cellular proliferation, such as a cancer, which may be associated with cereblon protein dysfunction and/or a GSPT1 dysfunction. In various further aspects, the disclosed compounds can selectively modulate the degradation of GSPT1 protein, i.e., the disclosed compounds can act as GSPT1 degraders. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

公开(公告)号：US20250122166A1

公开(公告)日：2025-04-17

申请号：US18707401

申请日：2022-11-02

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.

Inventor： Gisele A. NISHIGUCHI ,  Zoran RANKOVIC ,  Jeffery KLCO ,  Kevin MCGOWAN

IPC: C07D401/04 ,  A61K31/454 ,  A61P35/00

Abstract: In one aspect, the disclosure relates to substituted N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)benzamide analogs that useful as modulators of cereblon (CRBN) activity, methods of making same, pharmaceutical compositions comprising same, and methods of treating various clinical conditions and disorders using same, e.g., a disorder of uncontrolled cellular proliferation, such as a cancer, which may be associated with cereblon protein dysfunction. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

公开(公告)号：US20250034107A1

公开(公告)日：2025-01-30

申请号：US18712960

申请日：2022-11-17

Applicant: St. Jude Children's Research Hospital, Inc.

Inventor： Gisele A. NISHIGUCHI ,  Zoran RANKOVIC ,  Fatemeh KERAMATNIA

IPC: C07D401/04 ,  A61K31/454 ,  A61K31/5377

Abstract: In one aspect, the disclosure relates to substituted 2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)acetamide analogs that useful as modulators of GSPT1 and/or IKZF1 activity, methods of making same, pharmaceutical compositions comprising same, and methods of treating various clinical conditions and disorders using same, e.g., a disorder of uncontrolled cellular proliferation, such as a cancer, which may be associated with GSPT1 and/or IKZF1 protein dysfunction. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

公开(公告)号：US20240246941A1

公开(公告)日：2024-07-25

申请号：US18015657

申请日：2021-07-15

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.

Inventor： Ryan POTTS ,  Taosheng CHEN ,  Zoran RANKOVIC ,  Jaeki MIN ,  Wenwei LIN ,  Seung Wook YANG ,  Anand MAYASUNDARI

IPC: C07D405/12 ,  A61K31/4706 ,  A61K31/4709 ,  A61K45/06 ,  A61P35/00 ,  C07D215/46 ,  C07D401/12 ,  C07K7/08

CPC classification number: C07D405/12 ,  A61K31/4706 ,  A61K31/4709 ,  A61K45/06 ,  A61P35/00 ,  C07D215/46 ,  C07D401/12 ,  C07K7/08

Abstract: Testis-restricted melanoma antigen (MAGE) proteins are frequently hijacked in cancer and play a critical role in tumorigenesis. These proteins assemble with E3 ubiquitin ligases and function as substrate adaptors that direct the ubiquitination of novel targets, including key tumor suppressors. However, the development of MAGE-directed therapeutics heretofore has been extremely limited. In one aspect, the disclosure relates to compounds and peptides useful as inhibitors of MAGE-All: substrate interaction, methods of making same, pharmaceutical compositions comprising same, and methods of treating a disorder associated with a MAGE-All dysfunction. e.g., a cancer, using same. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.