MRK-740

MRK-740 for PRDM9

This probe is available from Sigma.

The negative control is available from Sigma.

  • overview
  • properties
  • co-crystal structures
overview
Probe Negative control

 

MRK-740

 

MRK-740-NC

A collaboration between MSD and the SGC has resulted in the discovery of MRK-740, a potent inhibitor of PRDM9 with a peptide competitive MOA. MRK-740 inhibits in vitro methylation of H3K4 with IC50 = 85 nM and shows more than 100-fold selectivity over other histone methyltransferases and other non-epigenetic targets. MRK-740 inhibits the methylation of H3K4 in cells with IC50 = 0.8 µM.  A control compound, MRK-740-NC, has also been developed which inhibits the in vitro methylation of H3K4 with IC50 > 100 µM. The use of this compound at 3 µM is recommended in cells.

Data relating to the discovery of this probe is being prepared for publication. In the meantime, in order to facilitate research by the community we are making this compound available through this website.

properties
Probe Negative control

 

MRK-740

 

MRK-740-NC

Physical and chemical properties for MRK-740
Molecular weight464.3
Molecular formulaC25H32N6O3
IUPAC name4-(3-(3,5-dimethoxy-phenyl)-1,2,4-oxadiazol-5-yl)-1-methyl-9-(2-methyl-pyridin-4-yl)-1,4,9-triaza-spiro[5.5]undecane
MollogP2.851
PSA65.67
No. of chiral centres0
No. of rotatable bonds7
No. of hydrogen bond acceptors5
No. of hydrogen bond donors0
Physical and chemical properties for MRK-740-NC (Negative Control)
Molecular weight449.2
Molecular formulaC25H31N5O3
IUPAC name4-(3-(3,5-dimethoxy-phenyl)-1,2,4-oxadiazol-5-yl)-1-methyl-9-phenyl-1,4,9-triaza-spiro[5.5]undecane
MollogP3.519
PSA56.81
No. of chiral centres0
No. of rotatable bonds5
No. of hydrogen bond acceptors6
No. of hydrogen bond donors0

SMILES:
MRK-740: CC1=CC(N2CCC3(CN(C4=NC(C5=CC(OC)=CC(OC)=C5)=NO4)CCN3C)CC2)=CC=N1
MRK-740-NC: CN1CCN(C2=NC(C3=CC(OC)=CC(OC)=C3)=NO2)CC14CCN(C5=CC=CC=C5)CC4

InChI:
MRK-740: 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

MRK-740-NC: InChI=1S/C25H31N5O3/c1-28-13-14-30(18-25(28)9-11-29(12-10-25)20-7-5-4-6-8-20)24-26-23(27-33-24)19-15-21(31-2)17-22(16-19)32-3/h4-8,15-17H,9-14,18H2,1-3H3

InChIKey:
MRK-740: NZYTZRHHBAJPKN-UHFFFAOYSA-N
MRK-740-NC: OACWMVMQWRVMAF-UHFFFAOYSA-N

selectivity profile
in vitro potency
cell based assay data
references
pk properties
co-crystal structures

Main features

  • Active form of mPRDM9 showing H3 peptide stabilized by C-terminus of SET domain (orange).
  • Overlay with inactive form of hPRDM9 which does not contain SAM or H3 peptide. Note the displacement of the helix (blue) which is stabilized in the active form (orange).
  • Binding of MRK-740 destabilizes the helix in similar manner to that of the apo-form (blue).
  • Overview of MRK-740 bound to mPRDM9 with SAM.
  • Detailed view of MRK-740 binding.
synthetic schemes
materials and methods
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