iPHF8 (inhibitor of PHF8) is a specific inhibitor of protein demethylase PHF8 with IC50 of 2.01 uM in Succinate-Glo JmjC demethylase assays, and SPR KD value of 240 nM.
iPHF8 displays 100-fold selectivity over a panel of demethylases including JMJD6, JARID2, KDM3A, KDM4C, KDM5C, and KDM6B, as well as JmjC domains from KDM7A and PHF2.
PHF8 mutants with I191 and F250 replaced by alanine (F250A and I191A) exhibits no binding with iPHF8.
iPHF8 treatment (1 uM, 24 h) led to a significant increase of cellular H3K9me1/2 and H4K20me1 levels, but not H3K4me2, H3K36me3, and H3K79me2 levels, also significantly increases YY1K258me2/3 levels, but decreases YY1K258me1.
iPHF8 exhibits EC50 of 2 µM in HeLa cells in cell proliferation assay.
iPHF8 regulates PY-ETC gene transcription, mitochondrial ROS, and tumor growth, exhibits EC50 values of 3 to 56 µM against different colon and lung cancer cell lines, with minimal toxicity in normal cells, exhibits potency and safety in suppressing tumor growth in cell-line- and patient-derived xenografts in vivo.