HDAC6 degrader-3

• CAT Number: I042283
• CAS Number: 2785404-83-1
• Molecular Formula: C41H41F4N7O11
• Molecular Weight: 883.80
• Purity: ≥95%
• Synonyms: 4-[[5-[8-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]octanoylamino]-2-methylbenzimidazol-1-yl]methyl]-3-fluoro-N-hydroxybenzamide;2,2,2-trifluoroacetic acid
• InChI: InChI=1S/C39H40FN7O9.C2HF3O2/c1-22-42-28-19-25(13-14-29(28)46(22)20-24-12-11-23(18-27(24)40)36(51)45-55)43-32(48)10-5-3-2-4-6-17-41-34(50)21-56-31-9-7-8-26-35(31)39(54)47(38(26)53)30-15-16-33(49)44-37(30)52;3-2(4,5)1(6)7/h7-9,11-14,18-19,30,55H,2-6,10,15-17,20-21H2,1H3,(H,41,50)(H,43,48)(H,45,51)(H,44,49,52);(H,6,7)
• InChIKey: YHRIRNOBNMKZIJ-UHFFFAOYSA-N
• SMILES: CC1=NC2=C(N1CC3=C(C=C(C=C3)C(=O)NO)F)C=CC(=C2)NC(=O)CCCCCCCNC(=O)COC4=CC=CC5=C4C(=O)N(C5=O)C6CCC(=O)NC6=O.C(=O)(C(F)(F)F)O

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 hyperacetylation of α-tubulin[1].
HDAC6 degrader-3 (compound B4; 100-1000 nM; 24 h) demonstrates potent HDAC6 degradation as well as hyperacetylation 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].

Reference

[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.
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