| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
Methionine adenosyltransferase 2A (MAT2A), the enzyme that catalyzes the synthesis of S-adenosylmethionine (SAM) from methionine and ATP.
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|---|---|
| ln Vitro |
MAT2A inhibitor 1 (compound 196) is a safe and efficient drug that can prevent and control cancer without having the toxicity and/or adverse effects of traditional medicines. Among these tumors are those that do not respond to conventional therapies such hormone therapy, radiation therapy, chemotherapy, or surgery [1].
MAT2A inhibitor 1 inhibits MAT2A enzymatic activity with an IC50 of less than 100 nM. It shows selective killing of MTAP-deficient cancer cells, which are dependent on MAT2A activity for survival. The compound demonstrates improved selectivity over conventional therapies. |
| ln Vivo |
MAT2A inhibitor 1 has shown in vivo anticancer activity in MTAP-deficient tumor models. It prevents and manages cancers while reducing or avoiding the toxicities associated with conventional therapies. The compound has demonstrated clinical activity in phase I trials.
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| Enzyme Assay |
MAT2A enzymatic activity is measured using radiometric or coupled enzyme assays. Recombinant MAT2A is incubated with methionine, ATP, and varying concentrations of the inhibitor. The production of S-adenosylmethionine (SAM) is quantified by HPLC or LC-MS to determine IC50 values.
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| Cell Assay |
MTAP-deficient cancer cell lines are treated with MAT2A inhibitor at various concentrations. Cell viability is assessed by MTT or CellTiter-Glo assays. SAM levels and methylation markers are measured by LC-MS. Apoptosis is evaluated by Annexin V/PI staining. Selectivity for MTAP-deficient over MTAP-proficient cells is assessed.
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| Animal Protocol |
MAT2A inhibitor is evaluated in mouse xenograft models of MTAP-deficient tumors. Tumor-bearing mice are treated with the inhibitor via oral administration. Tumor growth inhibition, SAM levels in tumor tissues, and survival are monitored. Pharmacokinetic and pharmacodynamic studies assess target engagement.
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| ADME/Pharmacokinetics |
MAT2A inhibitor 1 has molecular weight 526.61 and formula C30H22N6OS. In preclinical studies, the compound shows favorable pharmacokinetic properties. In phase I clinical trials, plasma concentrations increased with dose. The compound is suitable for oral administration.
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| Toxicity/Toxicokinetics |
In phase I clinical trials, MAT2A inhibitor AG-270/S095033 has demonstrated a manageable safety profile. The compound is reported to be a safe and effective agent that reduces or avoids the toxicities and side effects associated with conventional therapies.
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| References | |
| Additional Infomation |
MAT2A inhibitors refer to any drug that can inhibit methionine adenosine transferase II α (MAT2A).
MAT2A inhibitor is a novel therapeutic agent targeting cancer metabolism. Its mechanism involves inhibition of MAT2A, reducing SAM production and affecting methylation-dependent pathways in MTAP-deficient cancers. The compound has entered phase I clinical trials for advanced malignancies. Partial responses and stable disease have been observed in patients. |
| Molecular Formula |
C31H22N6OS
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|---|---|
| Molecular Weight |
526.610984325409
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| Exact Mass |
526.157
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| CAS # |
2201057-10-3
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| PubChem CID |
137296045
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
7.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
39
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| Complexity |
917
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(C)=NC2=CC=C(C=C12)C1C(N2C(=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=N2)NC=1NC1C=CC=CN=1)=O
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| InChi Key |
ZTNQNZDNHUAVEI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H22N6OS/c1-19-33-23-16-15-22(18-24(23)39-19)27-29(34-25-14-8-9-17-32-25)35-30-26(20-10-4-2-5-11-20)28(36-37(30)31(27)38)21-12-6-3-7-13-21/h2-18,35H,1H3,(H,32,34)
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| Chemical Name |
6-(2-methyl-1,3-benzothiazol-6-yl)-2,3-diphenyl-5-(pyridin-2-ylamino)-4H-pyrazolo[1,5-a]pyrimidin-7-one
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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 : ~5 mg/mL (~9.49 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8989 mL | 9.4947 mL | 18.9894 mL | |
| 5 mM | 0.3798 mL | 1.8989 mL | 3.7979 mL | |
| 10 mM | 0.1899 mL | 0.9495 mL | 1.8989 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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