sklb-23bb

Description: SKLB-23bb (23bb) is a novel, potent, orally bioavailable and selective inhibitor for HDAC6 with an IC50 of 17 nM and shows 25-fold and 200-fold selectivity relative to HDAC1 (IC50=422 nM) and HDAC8 (IC50=3398 nM), respectively. SKLB-23bb also has microtubule-disrupting ability. In vitro, 23bb presented low nanomolar antiproliferative effects against panel of cancer cell lines. Western blot analysis further confirmed that 23bb increased acetylation level of alpha-tubulin in vitro. 23bb 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, 23bb more effectively inhibited the tumor growth than SAHA even at a 4-fold reduced dose or ACY-1215 at the same dose.

References: J Med Chem. 2016 Feb 25; 59(4):1455-70.