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：US20220290251A1

公开(公告)日：2022-09-15

申请号：US17637510

申请日：2020-08-24

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

Inventor： Jun J. YANG ,  Jiyang YU

IPC: C12Q1/6886 ,  G01N33/574 ,  A61K31/506 ,  A61K31/5025 ,  A61P35/02

Abstract: Nucleic acid- and protein-based methods for identifying a patient sensitive to treatment with a tyrosine kinase inhibitor are provided, as is a method for treating a subject with a T-lineage hematological malignancy. Specifically, the method comprising determining activity levels of LCK nucleic acid or protein in a biological sample from a patient with a T-lineage hematological malignancy, wherein an increase in the activity levels of the LCK nucleic acid or protein in the biological sampled compared to a reference level indicates that the patient is sensitive to treatment with a tyrosine kinase inhibitor.