Quisinostat

875320-29-9

C21H26N6O2

DMSO : 50 mg/mL (126.75 mM; Need ultrasonic)

Epigenetics; Cell Cycle/DNA Damage

Quisinostat (JNJ-26481585) is an orally available, potent HDAC inhibitor with IC₅₀ values of 0.11 nM for HDAC1. IC50 & Target: IC50: 0.11 nM (HDAC1), 0.33 nM (HDAC2), 0.64 nM (HDAC4), 0.46 nM (HDAC10), 0.37 nM (HDAC11)^[1] In Vitro: 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]. In Vivo: JNJ-26481585 induces continuous H3 acetylation in tumor tissue in vivo. JNJ-26481585, a "second-generation" HDAC inhibitor with prolonged pharmacodynamic response in vivo. In agreement with the hypothesis, JNJ-26481585 showed superior efficacy compared with both standard of care agents and first-generation HDAC inhibitors in preclinical tumor models. These studies suggest that an HDAC inhibitor with continuous pharmacodynamic activity may show activity in solid tumor malignancies^[1].