Preclinical and first-in-human of Purinostat Mesylate, a novel selective HDAC I/IIb inhibitor, in relapsed or refractory multiple myeloma and lymphoma
Purinostat Mesylate (PM), a highly selective HDAC I/IIb inhibitor, exhibits excellent antitumor activity in multiple MM and lymphoma cell lines and multiple mouse models, outperforming the pan-HDAC inhibitor panobinostat or first-line/second-line multi-drug combinations. Different from panobinostat, bulk RNA-seq analysis results revealed that PM targeted essential tumor survival factors, and triggered inflammation and interferon responses. ScRNA-seq of 5TMM models further indicated that PM enhanced antitumor immunity by boosting monocyte- and T cell-mediated immune responses. Overall design: To investigate the effect of the I/IIb HDAC inhibitor Purostatin Mesylate (PM) on Multiple Myeloma (MM) gene expression, we treated MM.1S CDX model mice with Vehicle or PM (10 mg/kg) for 24 hours. Tumor tissues were then collected and total RNA was extracted using Trizol. Gene expression profile changes were analyzed using RNA-seq.