CAY10603 is a potent and selective inhibitor of HDAC6 (IC50 = 2 pM, as compared with 271, 252, 0.42, 6851, and 90.7 nM for HDAC1, 2, 3, 8, and 10, respectively)[1].

CAY10603 inhibits the proliferation and induces apoptosis of lung adenocarcinoma cells. In addition, CAY10603 works in concert with gefitinib to induce apoptosis in lung adenocarcinoma cell lines, in part due to EGFR instability and EGFR pathway inactivation[2].

In C57BL/6 mice model of endotoxemia, CAY10603 (intraperitoneal injection, 5 mg/kg, 2h) pretreatment significantly inhibits endotoxin-induced caspase-3 activation and reduces endotoxin-induced pulmonary edema form[3].

References:

[1]. Kozikowski A P, Tapadar S, Luchini D N, et al. Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: A new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6. Journal of Medicinal Chemistry, 2008, 51(15): 4370-4373.

[2]. Wang Z, et al. HDAC6 promotes cell proliferation and confers resistance to gefitinib in lung adenocarcinoma. Oncol Rep, 2016, 36(1): 589-97.

[3]. Yu J, Ma M, Ma Z, et al. HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions. Oncotarget, 2016,  7(34): 54714-54722.