FRC-222 is a CHD1 tandem chromodomain inhibitor with a K d of 0.15 μM and an IC50 of 0.18 μM. FRC-222 binds to the H3K4me3 binding site of CHD1 tandem chromodomain via aromatic cage interactions and extended ligand contacts. FRC-222 can be used for the research of prostate cancer [1].
In Vitro, FRC-222 (Compound 2n) binds to purified recombinant CHD1 tandem chromodomain with a Kd of 0.15 μM[1]. FRC-222 inhibits the interaction between purified recombinant CHD1 tandem chromodomain and H3K4me3 peptide with an IC50 of 0.49 μM[1]. FRC-222 (25-100 μM) engages endogenous full-length CHD1 in HEK293T cell lysate, competitively inhibiting its binding to LSD1-K114me3 peptide in a concentration-dependent manner[1]. FRC-222 (10 μM) shows high selectivity against purified LSD1, KMT9, METTL21A, EHMT2 (G9a), SET8, and NSD2 enzymes, with minimal inhibition of DNMT1[1]. FRC-222 (16 μM) shows high selectivity against purified TAF3, SPIN1, and PHF8 methyl-lysine reader domains, with no significant inhibition of H3K4me3 peptide binding[1]. FRC-222 (0.8-6 μM; 48 h) impairs the viability of PC-3M-Luc prostate cancer cells in a concentration-dependent manner, with significant inhibition observed at concentrations ≥1.8 μM[1]. FRC-222 (0.8-6 μM; 48 h) potently impairs the viability of 22Rv1 prostate cancer cells in a concentration-dependent manner, with significant inhibition observed at concentrations ≥1.8 μM[1].
References:
[1]. Greschik H, et al. Development of High-Affinity CHD1 Chromodomain Inhibitors. J Med Chem. Published online May 5, 2026.
In Vitro, FRC-222 (Compound 2n) binds to purified recombinant CHD1 tandem chromodomain with a Kd of 0.15 μM[1]. FRC-222 inhibits the interaction between purified recombinant CHD1 tandem chromodomain and H3K4me3 peptide with an IC50 of 0.49 μM[1]. FRC-222 (25-100 μM) engages endogenous full-length CHD1 in HEK293T cell lysate, competitively inhibiting its binding to LSD1-K114me3 peptide in a concentration-dependent manner[1]. FRC-222 (10 μM) shows high selectivity against purified LSD1, KMT9, METTL21A, EHMT2 (G9a), SET8, and NSD2 enzymes, with minimal inhibition of DNMT1[1]. FRC-222 (16 μM) shows high selectivity against purified TAF3, SPIN1, and PHF8 methyl-lysine reader domains, with no significant inhibition of H3K4me3 peptide binding[1]. FRC-222 (0.8-6 μM; 48 h) impairs the viability of PC-3M-Luc prostate cancer cells in a concentration-dependent manner, with significant inhibition observed at concentrations ≥1.8 μM[1]. FRC-222 (0.8-6 μM; 48 h) potently impairs the viability of 22Rv1 prostate cancer cells in a concentration-dependent manner, with significant inhibition observed at concentrations ≥1.8 μM[1].
References:
[1]. Greschik H, et al. Development of High-Affinity CHD1 Chromodomain Inhibitors. J Med Chem. Published online May 5, 2026.