Identification of New Shikonin Derivatives as Antitumor Agents Targeting STAT3 SH2 Domain.

ABSTRACT: Signal transducer and activator of transcription 3 (STAT3) is hyper-activated in diversiform human tumors and has been validated as an attractive therapeutic target. Current research showed that a natural product, shikonin, along with its synthetic analogues, is able to inhibit the activity of STAT3 potently. The potential space of shikonin in developing novel anti-cancer agents encouraged us to carry out the investigation of the probable binding mode with STAT3. From this foundation, we have designed new types of STAT3 SH2 inhibitors. Combined simulations were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. Among the entities, PMM-172 exhibited the best anti-proliferative activity against MDA-MB-231 cells with IC<

SUBMITTER: Qiu HY 

PROVIDER: S-EPMC5460289 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature