TAS-116 (pimitespib), a heat shock protein 90 inhibitor, shows efficacy in preclinical models of adult T-cell leukemia.

ABSTRACT: Adult T-cell leukemia/lymphoma (ATL) is a highly chemoresistant malignancy of peripheral T lymphocytes caused by human T-cell leukemia virus type 1 infection, for which there is an urgent need for more effective therapeutic options. The molecular chaperone heat shock protein 90 (HSP90) plays a crucial role in nuclear factor-κB (NF-κB)-mediated antiapoptosis in ATL cells, and HSP90 inhibitors are new candidate therapeutics for ATL. Accordingly, we investigated the anti-ATL effects of a novel oral HSP90 inhibitor, TAS-116 (pimitespib), and the mechanisms involved in ex vivo and in vivo preclinical models. TAS-116 achieved IC₅₀ values of less than 0.5 μmol/L in 10 ATL-related cell lines and less than 1 μmol/L in primary peripheral blood cells of nine ATL patients; no toxicity was o

SUBMITTER: Ikebe E 

PROVIDER: S-EPMC8819293 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature