Biological Activity
Quisinostat (JNJ-26481585) is an orally available, potent HDAC inhibitor with an IC50 of 0.11 nM for HDAC1.
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].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.
