Quisinostat (JNJ-26481585) (JNJ-26481585) is a novel second-generation HDAC inhibitor with highest potency for HDAC1 with IC50 of 0.11 nM, modest potent to HDACs 2, 4, 10, and 11; greater than 30-fold selectivity against HDACs 3, 5, 8, and 9 and lowest potency to HDACs 6 and 7.

HDAC1:0.11 nM

Quisinostat exerts broad-spectrum antiproliferative activity against a wide panel of cancer cell lines including lung, colon, breast, prostate, and ovarian cell lines at nanomolar concentrations. JNJ-26481585 shows activity toward all HDAC enzymes tested with highest potency in vitro observed toward recombinant HDAC1 (IC50, 0.11±0.03 nM), which is comparable with the potency observed toward HDAC1-immunoprecipitated complexes from tumor cells (IC50, 0.16±0.02 nM). Lowest in vitro potency is observed toward HDAC6, 7 and 9 (IC50, 32.1-119 nM) [1].

Quisinostat induces continuous H3 acetylation in tumor tissue in vivo. Quisinostat, a "second-generation" HDAC inhibitor with prolonged pharmacodynamic response in vivo. In agreement with the hypothesis, Quisinostat showed superior efficacy compared with both standard of care agents and first-generation HDAC inhibitors in preClinicalal tumor models. These studies suggest that an HDAC inhibitor with continuous pharmacodynamic activity may show activity in solid tumor malignancies[1].