PROTAC HDAC degrader-2 

PROTAC HDAC degrader-2 is a selective IIb HDACs PROTAC degrader, with DC₅₀s of 13 nM for HDAC6, 29 nM for HDAC10, respectively. PROTAC HDAC degrader-2 exhibits low cytotoxicity against hematological and solid cancer cell lines. PROTAC HDAC degrader-2 can be used for the chemical knockdown of class IIb HDACs. ( Pink: HDAC ligand : (HY-174471), Blue: E3 ligase CRBN Ligand (HY-131717), E3 ligase ligand-linker conjugate (HY-174473))^[1].

PROTAC HDAC degrader-2 (Compound AP1) (90 min) demonstrates inhibitory activity against HDAC6 and HDAC10, with IC₅₀ values of 0.04 μM and 0.022 μM in fluorogenic enzyme inhibition assays using Z-Lys(Ac)-AMC or Ac-spermidine-AMC as substrates^[1].

PROTAC HDAC degrader-2 (50-1000 nM, 0-1440 min) shows stability comparable to Tubastatin A (HY-13271A) in human plasma^[1].

PROTAC HDAC degrader-2 (1-5 μM, 24 h) shows proteasome-dependent and long-lasting degradation effect of the HDAC6 and HDAC10 in MM.1S cells and degrades HDAC6 and HDAC10 in MCF-7 cells^[1].

PROTAC HDAC degrader-2 (1 μM, 24 h) causes no relevant HDAC1, HDAC4, HDAC7 or HDAC8 degradation in MM.1S cells^[1].

PROTAC HDAC degrader-2 (1 μM, 24 h) induces upregulation of Ac-α-tubulin, a known substrate of HDAC6, comparable to Vorinostat (HY-10221)^[1].

PROTAC HDAC degrader-2 (1-5 μM, 6-24 h) induces neosubstrate degradation occurs via CRBN and not HDAC engagement in MM.1S cells^[1].

PROTAC HDAC degrader-2 (10 μM, 48 h) induces a significant prolongation of the G1-phase in MM.1S cells^[1].

PROTAC HDAC degrader-2 (1-5 μM, 24 h) does not affect the LC3-I and LC3-II levels in MM.1S cells^[1].

PROTAC HDAC degrader-2 (10 μM, 24 h) attenuates cell migration significantly in MDA-MB-231 cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

733.81

C₄₀H₄₃N₇O₇

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Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Zhai S, et al. Development and Characterization of the First Selective Class IIb Histone Deacetylase Degraders. J Med Chem. 2025 Jul 10;68(13):13793-13821.  [Content Brief]