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ABSTRACT:
SUBMITTER: Thakur A
PROVIDER: S-EPMC7238858 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Thakur Ashish A Tawa Gregory J GJ Henderson Mark J MJ Danchik Carina C Liu Suiyang S Shah Pranav P Wang Amy Q AQ Dunn Garrett G Kabir Md M Padilha Elias C EC Xu Xin X Simeonov Anton A Kharbanda Surender S Stone Richard R Grewal Gurmit G
Journal of medicinal chemistry 20200408 8
A series of quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC<sub>50</sub> < 10 nM) and selective against PI3Kγ, δ and HDAC6 enzymes and exhibited good antiproliferative activity against multiple cancer cell lines. The lead compound <b>48c</b>, induced necrosis in several mutant ...[more]