SCR-6920 is a potent and selective, oral PRMT5 inhibitor with IC50 of 1.48 nM.
SCR-6920 binds to substrate pocket, adjacent to the binding site of the cofactor SAM, does not affect the binding of MEP50 to PRMT5.
SCR-6920 shows no inhibitory activity against other TRPM family members such as PRMT1, PRMT3, PRMT6, and PRMT8 (IC50>50 uM).
SCR-6920 demonstrates broad antitumor activities on a range of tumors with IC50 of <600 nM for 15 out of 25 for lung cancer, 5 out of 6 for ovarian cancer, 9 out of 14 for breast cancer, 3 out of 3 for head and neck cancer, 3 out of 4 for bladder cancer, and 4 out of 4 for lymphoma.
SCR-6920 has IC50 values of 17.5 nmol/L (A375), 7.4 nmol/L (A549), 10.4 nmol/L (MDA-MB-468), 8.4 nmol/L (5637), 3.42 nmol/L (Z138), and 15.6 nmol/L (Raji), with minimal cytotoxicity to nonmalignant cell lines.
SCR-6920 regulates transcription profiles associated with DNA damage and angiogenesis in ovarian cancer.
SCR-6920 downregulates hypoxia-inducible factor-1α (HIF-1α) through the ubiquitin–proteasome degradation pathway, thereby reducing downstream VEGF expression and secretion.
SCR-6920 demonstrates a synergistic effect for SCR-6920 combined with bevacizumab against ovarian cancer.