MRK-740

• CAT Number: I015050
• CAS Number: 2387510-80-5
• Molecular Formula: C25H32N6O3
• Molecular Weight: 464.56
• Purity: ≥95%
• Synonyms: 3-(3,5-dimethoxyphenyl)-5-[1-methyl-9-(2-methylpyridin-4-yl)-1,4,9-triazaspiro[5.5]undecan-4-yl]-1,2,4-oxadiazole
• InChI: InChI=1S/C25H32N6O3/c1-18-13-20(5-8-26-18)30-9-6-25(7-10-30)17-31(12-11-29(25)2)24-27-23(28-34-24)19-14-21(32-3)16-22(15-19)33-4/h5,8,13-16H,6-7,9-12,17H2,1-4H3
• InChIKey: NZYTZRHHBAJPKN-UHFFFAOYSA-N
• SMILES: CC1=NC=CC(=C1)N2CCC3(CC2)CN(CCN3C)C4=NC(=NO4)C5=CC(=CC(=C5)OC)OC

MRK-740 is a potent, selective and substrate-competitive PRDM9 histone methyltransferase inhibitor with an IC50 of 80 nM. MRK-740 is more selective for PRDM9 than other histone methyltransferases and other non-epigenetic targets. MRK-740 reduces PRDM9-dependent trimethylation of H3K4 (IC50 = 0.8 µM)[1].
After 24?h of treatment, MRK-740 (3?μM) does not affect HEK293T cell growth at the IC90, but some toxicity is observed at 10?μM. MRK-740 is an equipotent inhibitor of H3K4 methylation in MCF7 cells. In cells, MRK-740 specifically and directly inhibits H3K4 methylation at endogenous PRDM9 target loci[1].

Reference

[1]. Abdellah Allali-Hassani, et al. Discovery of a Chemical Probe for PRDM9. Nat Commun. 2019 Dec 17;10(1):5759.
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