10.1021/acs.jmedchem.5b01342.s002 Zhuang Yang Zhuang Yang Taijin Wang Taijin Wang Fang Wang Fang Wang Ting Niu Ting Niu Zhuowei Liu Zhuowei Liu Xiaoxin Chen Xiaoxin Chen Chaofeng Long Chaofeng Long Minghai Tang Minghai Tang Dong Cao Dong Cao Xiaoyan Wang Xiaoyan Wang Wei Xiang Wei Xiang Yuyao Yi Yuyao Yi Liang Ma Liang Ma Jingsong You Jingsong You Lijuan Chen Lijuan Chen Discovery of Selective Histone Deacetylase 6 Inhibitors Using the Quinazoline as the Cap for the Treatment of Cancer American Chemical Society 2015 SAHA HDAC 6 inhibitor nanomolar antiproliferative effects Western blot analysis HCT vivo efficacy evaluations MV B cell lymphoma Romas xenografts ACY histone deacetylase 6 cancer cell lines 23 bb Selective Histone Deacetylase 6 Inhibitors IC 2015-10-06 00:00:00 Dataset https://acs.figshare.com/articles/dataset/Discovery_of_Selective_Histone_Deacetylase_6_Inhibitors_Using_the_Quinazoline_as_the_Cap_for_the_Treatment_of_Cancer/2124883 Novel selective histone deacetylase 6 (HDAC6) inhibitors using the quinazoline as the cap were designed, synthesized, and evaluated for HDAC enzymatic assays. <i>N</i>-Hydroxy-4-(2-methoxy-5-(methyl­(2-methylquinazolin-4-yl)­amino)­phenoxy)­butanamide, <b>23bb</b>, was the most potent selective inhibitor for HDAC6 with an IC<sub>50</sub> of 17 nM and showed 25-fold and 200-fold selectivity relative to HDAC1 and HDAC8, respectively. In vitro, <b>23bb</b> presented low nanomolar antiproliferative effects against panel of cancer cell lines. Western blot analysis further confirmed that <b>23bb</b> increased acetylation level of α-tubulin in vitro. <b>23bb</b> has a good pharmacokinetic profile with oral bioavailability of 47.0% in rats. In in vivo efficacy evaluations of colorectal HCT116, acute myelocytic leukemia MV4-11, and B cell lymphoma Romas xenografts, <b>23bb</b> more effectively inhibited the tumor growth than SAHA even at a 4-fold reduced dose or ACY-1215 at the same dose. Our results indicated that <b>23bb</b> is a potent oral anticancer candidate for selective HDAC6 inhibitor and deserves further investigation.