MRK-740

Protein target name:

PRDM9

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 3 uM

Probe Availability

TOCRIS

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Histone methyltransferase

HUGO symbol:

HGNC:13994

Entrez gene ID:

56979

Target alias:

PFM6; KMT8B; MSBP3; ZNF899; MEISETZ

Probe Details

Chemical Probes Portal ID:

CPP1836

Probe alias:

MRK740

PubChem CID:

137331596

SMILES string:

Cc1cc(ccn1)N1CCC2(CC1)CN(CCN2C)c1nc(c2cc(cc(c2)OC)OC)no1

InChi Key:

NZYTZRHHBAJPKN-UHFFFAOYSA-N

Control compound:

MRK-740-NC

Physico-chemical properties

Solubility - preferred solvent:

DMSO

NMR:

1H NMR (400MHz, CD3OD) δ 7.98 (d, J = 6.2 Hz, 1H), 7.08 (d, J = 2.3 Hz, 2H), 6.68 (d, J = 2.6 Hz, 1H), 6.64 (dd, J = 6.3, 2.6 Hz, 1H), 6.61 (t, J = 2.3 Hz, 1H), 3.26 (ddd, J = 13.6, 10.7, 3.3 Hz, 2H), 2.87 – 2.83 (m, 2H), 2.38 (s, 3H), 2.38 (s, 3H), 1.98 (ddd, J = 14.8, 10.8, 4.6 Hz, 2H), 1.66 (dd, J = 13.9, 3.9 Hz, 2H)

Storage Recommendations

Storage (dry powder):

- 20C

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

80 ± 16 nM

PDB ID for probe-target interaction (3D structure):

6NM4

Structure-activity relationship:

yes

Off target activity

Potency assay (off target):

Enzyme Activity Assay

Selectivity against non-family targets:

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

In cell validation

On target activity in cells

Potency in cells:

IC50

0.8 uM

Potency assay (cells):

H3K4 methylation assay

Target engagement assay (cells):

NanoLuciferase thermal shift assay (NALTSA)

Off target activity in cells

Potency assay, off target (cells):

Eurofins Panlabs

Selectivity against nonfamily targets (cells):

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.

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

10 uM after 4 days.

Primary Reference

Reference (doi):

10.1038/s41467-019-13652-x

Reference (PMID):

31848333

MRK-740

Probe Availability

Probe Information

Target Details

PFM6; KMT8B; MSBP3; ZNF899; MEISETZ

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

Supporting Organizations

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MRK-740

Probe Availability

Probe Information

Target Details

PFM6; KMT8B; MSBP3; ZNF899; MEISETZ

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

Primary Reference

Supporting Organizations

Interested in supporting the portal?