1084-12-4Relevant articles and documents
Prospective evaluation and success of a machine learning hit-to-lead drug development program against phosphatidylinositol 3-kinase α
Kaiser, Thomas M.,Dentmon, Zackery W.,Burger, Pieter B.,Shi, Qi,Snyder, James P.,Du, Yuhong,Fu, Haian,Liotta, Dennis C.
supporting information, p. 25 - 43 (2021/05/28)
As a result of the rapidly increasing cost of drug development, efficient methods for early identification of compounds with a high probability of clinical success are needed. Herein, we describe a cheminformatics protocol which dramatically increases quality candidate identification and should reduce the attrition rate of compounds entering the clinic, increasing the cost-effectiveness of drug development. Against the oncology target phosphatidylinositol 3-kinase α, all five compounds synthesized from the protocol were found to have low nanomolar activity. We therefore propose that our protocol can be used as a tool for reducing the synthetic burden required for hit-to-lead optimization.
Discovery of a Novel Series of 7-Azaindole Scaffold Derivatives as PI3K Inhibitors with Potent Activity
Yang, Chengbin,Zhang, Xi,Wang, Yi,Yang, Yongtai,Liu, Xiaofeng,Deng, Mingli,Jia, Yu,Ling, Yun,Meng, Ling-Hua,Zhou, Yaming
supporting information, p. 875 - 880 (2017/08/16)
The phosphoinositide 3-kinase (PI3K) inhibitors potently inhibit the signaling pathway of PI3K/AKT/mTOR, which provides a promising new approach for the molecularly targeted cancer therapy. In this work, a novel series of 7-azaindole scaffold derivatives was discovered by the fragment-based growing strategy. The structure-activity relationship profiles identified that the 7-azaindole scaffold derivatives exhibit potent activity against PI3K at molecular and cellular levels as well as cell proliferation in a panel of human tumor cells.
NOVEL PYRIDOPYRIMIDINE DERIVATIVES AND USE THEREOF
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Page/Page column 16-17, (2012/09/25)
The invention provides novel substituted pyridopyrimidines represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof, and a composition comprising these compounds. The compounds provided can be used as inhibitors of the phosphoinositide 3′ OH kinase family (PI3K) for the treatment of inflammatory diseases, cancer, cardiovascular diseases, allergy, asthma and autoimmune disorders.