Inhibitor of PRDM9



  • PRDM9
  • Inhibitor
  • up to 3 uM

In Vitro Validations

Uniprot ID: Q9NQV7
Target Class: Epigenetic
Target SubClass: Histone methyltransferase
Potency: IC50
Potency Value: 80 ± 16 nM
PDB ID for probe-target interaction (3D structure): 6NM4
Structure-activity relationship: yes
Target aliases:
Histone-lysine N-methyltransferase PRDM9, PFM6, PR ...

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Enzyme Activity Assay
Probe Selectivity in Vitro:
Selectivity against 32 methyltransferases (MTs) were tested at 1 µM and 10 µM of compounds. PRDM9 was the only methyltransferase in a panel of MTs that was inhibited by MRK-740
Potency assay, off target (cells): Eurofins Panlabs
Probe Selectivity in Cell:
MRK-740 was profiled in a customized panel of 108 enzymes and receptors at Eurofins Panlabs Discovery Services, Taiwan. MRK-740 demonstrated significant (>50% at 10 µM) binding only to Adrenergic α2B, Histamine H3, Muscarinic M2 and Opiate µ receptors. Functional assessment for these four GPCRs in agonist and antagonist mode revealed no functional activity on Adrenergic α2B, Histamine H3 & Muscarinic M2 receptors, and some potential agonistic activity at the Opiate µ receptor.
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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

MRK-740 is a probe that shows good biochemical target-based potency (80 nM), selectivity against other methyltransferases as well as against a customized panel of 108 enzymes and receptors at Eurofins Panlabs Discovery Services.  Moreover, it has also been shown to be sufficiently potent (0.8 uM) to be a useful probe to study the biology of PRMD9 in whole cells. The fact that a crystal structure of MRK-740 bound to PRMT9 is available that shows the mode of target engagement is a strong positive. On the other hand, because it shows cytotoxicity in HEK293 cells at 10 uM, as noted above this probe should not be used at concentrations above ~5 uM. It is unclear what the mechanism of cytotoxicity (both it and its inactive counterpart MRK-740-NC show similar off-target cytotoxicity). While the probe has a good drug-like structure, the methylpyridine structure suggests that it may inhibit kinase targets at higher concentrations, and since no broad kinase data has been published, this possibility has not been definitively ruled out. In addition, no pharmacokinetic data is available which should be generated independently if this probe is to be used in vivo.

(last updated: 4 Nov 2020 )

SERP+ Ratings

In Cell Rating

SERP+ Comments:

MRK-740 is a highly selective probe without any significant off-targets in vitro or in cells with IC50 = 80 nM of cellular potency. We would recommend repeating the cytotoxicity assay in your relevant cell lines when you perform the experiment. It is important to also test the negative control in parallel as its observed cytotoxicity might be related to chemical structure, and not a target effect.

(last updated: 22 Mar 2023 )

Portal Comments

In a 2023 study, Hu et al. evaluated MRK-740 in live-cell assays for Phospholipidosis induction, cautioning about adverse effects at concentrations equal or exceeding 1 uM. (DOI: 10.1016/j.chembiol.2023.09.003)

(last updated: 7 Nov 2023)