FRC-303

FRC-303 is a CHD1 inhibitor with a K d of 0.14 μM and an IC₅₀ of 0.18 μM. FRC-303 binds to the H3K4me3 binding site of CHD1 tandem chromodomain, forms aromatic cage interactions and extended ligand contacts, acts as a methyl-lysine mimic, and occupies natural peptide ligand-binding regions. FRC-303 can be used for the research of prostate cancer ^[1].

In Vitro, FRC-303 (Compound 2s) binds to purified recombinant CHD1 tandem chromodomain with a Kd of 0.14 μM^[1]. FRC-303 inhibits the interaction between purified recombinant CHD1 tandem chromodomain and H3K4me3 peptide in a TR-FRET assay with an IC₅₀ of 0.18 μM^[1]. FRC-303 engages exogenous CHD1 tandem chromodomain in transfected HEK293T cells with an EC50 of 15 μM in a NanoBRET assay^[1]. FRC-303 (25-100 μM) dose-dependently inhibits binding of endogenous CHD1 to LSD1-K114me3 peptide in HEK293T cell lysates^[1]. FRC-303 (10 μM) does not inhibit the catalytic activity of purified LSD1, KMT9, METTL21A, EHMT2 (G9a), SET8, or NSD2 enzymes^[1]. FRC-303 (16 μM) does not inhibit H3K4me3 peptide binding to purified TAF3, SPIN1, or PHF8 reader domains^[1]. FRC-303 (0.8-6 μM; 48 h) impairs viability of PC-3M-Luc prostate cancer cells, with viability reduced to ~5% at 6 μM^[1]. FRC-303 (0.8-6 μM; 48 h) potently impairs viability of 22Rv1 prostate cancer cells, with viability reduced to ~5% or lower at concentrations ≥2.7 μM^[1].

References:
[1]. Greschik H, et al. Development of High-Affinity CHD1 Chromodomain Inhibitors. J Med Chem. Published online May 5, 2026.