Development of the phenylpyrazolo[3,4-d]pyrimidine-based, insulin-like growth factor receptor/Src/AXL-targeting small molecule kinase inhibitor.

ABSTRACT: Rationale: The type I insulin-like growth factor receptor (IGF-1R) signaling pathway plays key roles in the development and progression of numerous types of human cancers, and Src and AXL have been found to confer resistance to anti-IGF-1R therapies. Hence, co-targeting Src and AXL may be an effective strategy to overcome resistance to anti-IGF-1R therapies. However, pharmacologic targeting of these three kinases may result in enhanced toxicity. Therefore, the development of novel multitarget anticancer drugs that block IGF-1R, Src, and AXL is urgently needed. Methods: We synthesized a series of phenylpyrazolo[3,4-d]pyrimidine (PP)-based compounds, wherein the PP module was conjugated with 2,4-bis-arylamino-1,3-pyrimidines (I2) via a copper(I)-catalyzed alkyne-azide cy

SUBMITTER: Lee HJ 

PROVIDER: S-EPMC7778606 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature