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• W4361959728 abstract "<div>AbstractPurpose:<p>This study was to perform preclinical evaluation of a novel class I and IIb HDAC-selective inhibitor, purinostat mesylate, for the treatment of Ph⁺ B-cell acute lymphoblastic leukemia (B-ALL).</p>Experimental Design:<p>Biochemical assays were used to test enzymatic activity inhibition of purinostat mesylate. Ph⁺ leukemic cell lines and patient cells were used to evaluate purinostat mesylate activity <i>in vitro</i>. BL-2 secondary transplantation Ph⁺ B-ALL mouse model was used to validate its efficacy, mechanism, and pharmacokinetics properties <i>in vivo</i>. <i>BCR-ABL(T315I)</i>–induced primary B-ALL mouse model and PDX mouse model derived from relapsed Ph⁺ B-ALL patient post TKI treatment were used to determine the antitumor effect of purinostat mesylate for refractory or relapsed Ph⁺ B-ALL. Long-term toxicity and hERG blockade assays were used to safety evaluation of purinostat mesylate.</p>Results:<p>Purinostat mesylate, a class I and IIb HDAC highly selective inhibitor, exhibited robust antitumor activity in hematologic cancers. Purinostat mesylate at low nanomolar concentration induced apoptosis, and downregulated BCR-ABL and c-MYC expression in Ph⁺ leukemia cell lines and primary Ph⁺ B-ALL cells from relapsed patients. Purinostat mesylate efficiently attenuated Ph⁺ B-ALL progression and significantly prolonged the survival both in BL-2 secondary transplantation model with clinical patient symptoms of Ph⁺ B-ALL, <i>BCR-ABL(T315I)</i>–induced primary B-ALL mouse model, and PDX model derived from patients with relapsed Ph⁺ B-ALL post TKI treatment. In addition, purinostat mesylate possesses favorable pharmacokinetics and low toxicity properties.</p>Conclusions:<p>Purinostat mesylate provides a new therapeutic strategy for patients with Ph⁺ B-ALL, including those who relapse after TKI treatment.</p></div>" @default.
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• W4361959728 date "2023-03-31" @default.
• W4361959728 modified "2023-10-06" @default.
• W4361959728 title "Data from Purinostat Mesylate Is a Uniquely Potent and Selective Inhibitor of HDACs for the Treatment of <i>BCR-ABL</i>–Induced B-Cell Acute Lymphoblastic Leukemia" @default.
• W4361959728 doi "https://doi.org/10.1158/1078-0432.c.6528252" @default.
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