AC-340 

AC-340 is a potent hybrid VDR agonist/HDAC inhibitor. AC-340 superinduces VDR target genes (e.g., CYP24A1) and inhibits HDAC6 (IC₅₀ = 0.37 μM) with ~10-fold selectivity over HDAC2. AC-340 induces VDR hyperagonism by causing widespread protein hyperacetylation (e.g., tubulin and H3K9/K27), which leads to elevated H3K27 acetylation on VDR target genes. AC-340 can be used for melanoma cancer research^[1].

AC-340 (10 μM, 6 h) induces robust protein hyperacetylation in B16-F10 cells, such as tubulin acetylation (targeted by HDAC6) and acetylation of histone H3 lysines 9 and 27^[1].
AC-340 (10 μM, 24 h) upregulates both VDR gene and protein expression in mouse B16-F10 cells, but in human A375 and SK-MEL-28 cells, it enhances VDR protein without affecting its gene expression^[1].
AC-340 (2 h) induces VDR recruitment to the Spp1 VDRE to a level similar to Calcitriol (1,25D) (HY-10002), but it uniquely leads to a significant induction of H3K27 acetylation at this locus in B16-F10 cells^[1].
AC-340 binds the VDR by forming more extensive interactions with the coactivator binding surface than the natural ligand 1,25D^[1].

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

476.67

C₂₆H₄₀N₂O₄S

CCC(CC)(C1=CC=C(C=C1)OCCCC(NO)=O)C2=NC(C)=C(S2)CCC(C(C)(C)C)O

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• [1]. Sarmadi F, et al. Hyperagonism of a Vitamin D Receptor Agonist/Histone Deacetylase Inhibitor Hybrid Molecule. J Med Chem. 2025 Oct 9;68(19):20675-20688.