CAY-10603

A highly potent and selective HDAC6 inhibitor with IC50 of 2 pM; 200-fold less potent for HDAC3 (IC50=0.42 nM) and no inhibition on HDAC1/2/8/10 (IC50> 100 nM) ; downregulates the levels of EGFR protein and synergizes with gefitinib to induce apoptosis of the lung adenocarcinoma cell lines. (In Vitro) :CAY10603 (Compound 7) shows potent inhibitory activities against pancreatic cancer cell lines, with IC50s of 1, 0.3, 0.1, 0.1, 0.6, <1, 0.5 μM for BxPC-3, HupT3, Mia Paca-2, Panc 04.03, SU.86.86, HMEC, HPDE6c7, respectively. CAY10603 (100 nM, 200-300 nM) is active against both the Mia Paca-2 and Panc04.03 cell lines. CAY10603 inhibits HDAC6 deacetylase activity, and supresses the proliferation of lung adenocarcinoma cells. CAY10603 also induces apoptosis of lung adenocarcinoma cells. Furthermore, CAY10603 synergizes with gefitinib to induce apoptosis in lung adenocarcinoma cell lines, partly through the destabilization of EGFR and inactivation of the EGFR pathway.