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| Targets |
MRK-740 targets PRDM9, a histone methyltransferase that catalyzes the trimethylation of histone H3 at lysine 4 (H3K4). PRDM9 plays a critical role in meiotic recombination by determining the locations of recombination hotspots. MRK-740 acts as a substrate-competitive inhibitor, binding to the enzyme's substrate-binding site. The compound is more selective for PRDM9 than other histone methyltransferases and other non-epigenetic targets.
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| ln Vitro |
MRK-740 (3 μM) did not impact HEK293T cell growth at IC90 after a 24-hour treatment period; however, at 10 μM, some toxicity was noted. The matching reagent for H3K4 methylation in MCF7 cells is MRK-740. The PRDM9 target's H3K4 methylation is directly inhibited by MRK-740 buffer in cells [1].
In vitro, MRK-740 inhibits PRDM9-mediated H3K4 methylation with an IC50 of 80-85 nM in cell-free enzyme assays. It displays >100-fold selectivity over other histone methyltransferases. In cellular assays, MRK-740 reduces PRDM9-dependent H3K4 trimethylation with an IC50 of 0.8 µM. At 3 µM, the compound does not impact HEK293T cell growth at IC90 after 24 hours, but at 10 µM, some toxicity is noted. |
| ln Vivo |
In vivo activity data for MRK-740 are not extensively detailed in the available sources. As a chemical probe supplied by the Structural Genomics Consortium, it is primarily intended for research use to study PRDM9 function in meiosis and recombination. The compound's high selectivity and potency make it a valuable tool for investigating the role of PRDM9 in genomic stability and disease, though specific in vivo efficacy data have not been reported.
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| Enzyme Assay |
The in vitro enzyme assay for MRK-740 involves measuring the inhibition of PRDM9-mediated H3K4 methylation. Recombinant PRDM9 enzyme is incubated with a histone H3 peptide substrate and SAM in the presence of varying concentrations of the compound. Methylation is quantified using scintillation proximity or fluorescence-based detection methods. The IC50 value (80-85 nM) is determined by fitting dose-response curves to the inhibition data.
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| Cell Assay |
Cellular assays are performed using cells treated with MRK-740 at varying concentrations. H3K4 trimethylation is assessed by Western blotting using H3K4me3-specific antibodies. The compound's cellular potency (IC50 = 0.8 µM) is calculated from dose-response curves. Cell viability assays may be performed to assess compound toxicity at concentrations above 3 µM.
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| Animal Protocol |
In vivo animal studies for MRK-740 are not detailed in the available sources. The compound is provided as a chemical probe by the Structural Genomics Consortium for research purposes. A reference publication describing its discovery is available (Allali-Hassani et al, 2019, Nat. Commun. 10 5759; PMID: 31848333). Specific animal models and dosing regimens have not been described.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for MRK-740 are not available in the provided sources. The compound has a molecular weight of 464.56 g/mol, a formula of C25H32N6O3, and a calculated logP of 3.5. It is typically stored at -20°C. Specific PK parameters such as half-life, bioavailability, volume of distribution, and clearance have not been reported in the available literature or supplier documentation.
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| Toxicity/Toxicokinetics |
Toxicity data for MRK-740 are limited. At 3 µM, the compound does not impact HEK293T cell growth, but at 10 µM, some toxicity is noted. As a research compound used as a chemical probe, it is not intended for therapeutic use. Specific toxicological profiles, including genotoxicity, cardiotoxicity, or organ-specific toxicity, have not been characterized.
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| References | |
| Additional Infomation |
MRK-740 is a chemical probe supplied by the Structural Genomics Consortium (SGC) for research purposes. A reference publication describing its discovery is available (Allali-Hassani et al, 2019, Nat. Commun. 10 5759; PMID: 31848333). The compound is available from commercial suppliers for research use only and is not approved for human therapeutic use. It serves as a valuable tool for studying PRDM9 function in meiosis, recombination, and genomic stability.
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| Molecular Formula |
C25H32N6O3
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|---|---|
| Molecular Weight |
464.5600
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| Exact Mass |
464.253
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| CAS # |
2387510-80-5
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| Related CAS # |
2387510-80-5;MRK-740 HCl;
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| PubChem CID |
137331596
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| Appearance |
White to yellow solid powder
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| LogP |
3.5
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
651
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(=NC(C2C([H])=C(C([H])=C(C=2[H])OC([H])([H])[H])OC([H])([H])[H])=N1)N1C([H])([H])C([H])([H])N(C([H])([H])[H])C2(C1([H])[H])C([H])([H])C([H])([H])N(C1C([H])=C([H])N=C(C([H])([H])[H])C=1[H])C([H])([H])C2([H])[H]
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| InChi Key |
NZYTZRHHBAJPKN-UHFFFAOYSA-N
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| InChi Code |
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
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| Chemical Name |
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
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~40 mg/mL (~86.10 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.38 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.38 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1526 mL | 10.7629 mL | 21.5257 mL | |
| 5 mM | 0.4305 mL | 2.1526 mL | 4.3051 mL | |
| 10 mM | 0.2153 mL | 1.0763 mL | 2.1526 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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