WT-161

WT-161 is a potent and selective HDAC6 inhibitor with an IC₅₀ of 0.40 nM^[1]. WT-161 also inhibits metallo-β-lactamase domain-containing protein 2 (MBLAC2)^[2]. IC50 & Target: IC50: 0.40 nM (HDAC6), 51.61 nM (HDAC3)^[1] In Vitro: WT161 selectively inhibits HDAC6 and dramatically increases levels of acetylated α-tubulin (Ac-α-tubulin) with little effect on global lysine acetylation. WT161 induces significant toxicity in all multiple myeloma cell lines tested, with IC₅₀s between 1.5 and 4.7 µM . WT161 in combination with bortezomib triggers significant accumulation of polyubiquitinated proteins and cell stress, followed by caspase activation and apoptosis. More importantly, this combination treatment is effective in bortezomib-resistant cells and in the presence of bone marrow stromal cells, which have been shown to mediate multiple myeloma cell drug resistance^[1]. In Vivo: WT161 shows toxicity at 100 mg/kg i.p., but WT161 is well tolerated at 50 mg/kg i.p.. Bortezomib combined with WT161 demonstrates a significant antitumor effect^[1].