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.
Probe | Negative control | |
![]() |
| ![]() |
MRK-740 |
| MRK-740-NC |
Physical and chemical properties for MRK-740 | |
Molecular weight | 464.3 |
Molecular formula | C25H32N6O3 |
IUPAC name | 4-(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 |
MollogP | 2.851 |
PSA | 65.67 |
No. of chiral centres | 0 |
No. of rotatable bonds | 7 |
No. of hydrogen bond acceptors | 5 |
No. of hydrogen bond donors | 0 |
Physical and chemical properties for MRK-740-NC (Negative Control) | |
Molecular weight | 449.2 |
Molecular formula | C25H31N5O3 |
IUPAC name | 4-(3-(3,5-dimethoxy-phenyl)-1,2,4-oxadiazol-5-yl)-1-methyl-9-phenyl-1,4,9-triaza-spiro[5.5]undecane |
MollogP | 3.519 |
PSA | 56.81 |
No. of chiral centres | 0 |
No. of rotatable bonds | 5 |
No. of hydrogen bond acceptors | 6 |
No. of hydrogen bond donors | 0 |
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
Main features