HDAC6 degrader-3 is a potent and selective HDAC6 degrader via ternary complex formation and the ubiquitin-proteasome pathway with a DC50 value of 19.4 nM. HDAC6 degrader-3 has IC50s of 4.54 nM and 0.647 μM for HDAC6 and HDAC1, respectively. HDAC6 degrader-3 causes strong peracetylation of α-tubulin.
HDAC6 degrader-3 (compound B4; 100-1000 nM; 24 h) demonstrates potent HDAC6 degradation as well as peracetylation of α-tubulin[1]. HDAC6 degrader-3 (0.5-50 μM; 72 h) does not display any inhibitory effects on the cellular viability of leukemic cell lines (697, HL-60, KASUMI-1, MV4-11, REH, THP-1, SKNO-1, MOLM-13)[1].
References:
[1]. Laura Sinatra, et al. Solid-Phase Synthesis of Cereblon-Recruiting Selective Histone Deacetylase 6 Degraders (HDAC6 PROTACs) with Antileukemic Activity. J Med Chem. 2022 Dec 22;65(24):16860-16878.