HDAC6-IN-1

SKLB-23bb is an orally bioavailable and selective HDAC6 inhibitor with IC50 of less than 100 nM in most cell lines tested; it can be used to disrupt microtubule activity.

SKLB-23bb has toxic effects at low submolar levels in a range of solid and hematological tumor cell lines. Unlike reported selective HDAC6 inhibition, SKLB-23bb is more potent against solid tumors. SKLB-23bb selectively inhibits intracellular HDAC6, but its antitumor activity is independent of HDAC6. It can bind to the colchicine site of β-tubulin and is a microtubule polymerization inhibitor. SKLB-23bb also can arrest tumor cells in the G2-M phase and induce apoptosis.

In a solid tumor model, oral administration of SKLB-23bb can effectively inhibit tumor growth. It has favorable pharmacokinetic properties and is orally active.