Antitumor activity of a novel oral signal transducer and activator of transcription 3 inhibitor YHO-1701.

ABSTRACT: The signal transducer and activator of transcription 3 (STAT3) signaling pathway is a key mediator of cancer cell proliferation, survival and invasion. Aberrant STAT3 has been demonstrated in various malignant cancers. YHO-1701 is a novel quinolinecarboxamide derivative generated from STX-0119. Here, we examined the effect of YHO-1701 on STAT3 and evaluated antitumor activity of YHO-1701 as a single agent and in combination. YHO-1701 inhibited STAT3-SH2 binding to phospho-Tyr peptide selectively and more potently than STX-0119 in biochemical assays. Molecular docking studies with STAT3 suggested more stable interaction of YHO-1701 with the SH2 domain. YHO-1701 exhibited approximately 10-fold stronger activity than STX-0119 in abrogating the STAT3 signaling pathway of human oral cancer cell

SUBMITTER: Nishisaka F 

PROVIDER: S-EPMC7226286 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature