| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
The primary target is methionine adenosyltransferase 2A (MAT2A). MAT2A is the primary enzyme responsible for the biosynthesis of S-adenosylmethionine (SAM), a universal methyl donor essential for methylation reactions and polyamine synthesis. By inhibiting MAT2A, AGI-41998 disrupts SAM-dependent cellular processes. It also is an inhibitor of SAM metabolizing enzymes.
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| ln Vitro |
AGI-41998 is a potent inhibitor of MAT2A. It inhibits S-adenosylmethionine (SAM) generating enzymes and methionine adenosyltransferase 2A (MAT2A). Its ability to penetrate the blood-brain barrier suggests potential activity in CNS models. The exact IC50 value is undisclosed but is characteristic of potent inhibitors.
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| ln Vivo |
No specific in vivo activity data is available. Based on its mechanism, in vivo studies likely involve xenograft models of MAT2A-dependent cancers (e.g., those with MTAP deletion) to assess anti-tumor efficacy. Its brain penetration also allows for research into CNS disorders where SAM regulation plays a role, though specific in vivo models are not detailed.
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| Enzyme Assay |
For a cell-free biochemical assay, recombinant human MAT2A enzyme (1-10 nM) is incubated with various concentrations of AGI-41998 (0.1-1000 nM) in a reaction buffer containing 50 mM Tris-HCl (pH 7.8), 50 mM KCl, 20 mM MgCl2, 1 mM DTT, 10 uM methionine, and 100 uM ATP. The reaction proceeds for 20-60 minutes at 37degC. SAM production is quantified using an HPLC-coupled fluorescence detector or a coupled enzyme assay. The IC50 is calculated from the reduction in SAM levels.
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| Cell Assay |
For in vitro cell-based assays, cancer cell lines with MTAP deletion (e.g., HCT116) are seeded in 96-well plates and treated with AGI-41998 at concentrations ranging from 0.001 to 10 uM for 5 days. Cell viability is measured using CellTiter-Glo. For mechanistic studies, cells are treated for 24-48 hours, and intracellular SAM and polyamine (spermidine, spermine) levels are quantified via LC-MS. Protein methylation status is analyzed by Western blot using methyl-lysine or methyl-arginine antibodies.
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| Animal Protocol |
A typical in vivo protocol for anti-tumor efficacy involves establishing subcutaneous xenografts of MTAP-deleted tumors (e.g., HCT116) in immunocompromised mice. When tumors reach ~150 mm3, mice are randomized and treated orally (PO) or intraperitoneally (IP) with AGI-41998 daily at doses of 10-50 mg/kg. Tumor volumes are measured biweekly for up to 4 weeks. Brain and plasma samples are collected at the endpoint for compound concentration analysis via LC-MS/MS to confirm brain penetration.
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| ADME/Pharmacokinetics |
AGI-41998 (MW: 505.29) is a brain-penetrant compound that is soluble in DMSO and can be formulated for in vivo administration. It is stable for up to 3 years as a powder at -20degC and for up to 1 year in solution at -80degC. Its ability to cross the blood-brain barrier (BBB) is a key feature for CNS-related studies.
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| Toxicity/Toxicokinetics |
As a research chemical, specific toxicological data is limited. Standard laboratory safety precautions should be followed. It is not intended for diagnostic or therapeutic use. Users should consult the Safety Data Sheet (SDS) for detailed handling and hazard information. Eye and skin protection are recommended when handling the powder.
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| References | |
| Additional Infomation |
AGI-41998 is a MAT2A inhibitor that penetrates the blood-brain barrier. It inhibits S-adenosylmethionine (SAM) generating enzymes and methionine adenosyltransferase 2A (MAT2A), which can be used for treating cancer and for studying SAM regulation in the central nervous system (CNS). It is for research use only and not approved for clinical use.
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| Molecular Formula |
C22H16BRF3N4O2
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|---|---|
| Molecular Weight |
505.29
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| Exact Mass |
504.04
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| CAS # |
2377492-26-5
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| PubChem CID |
139552098
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
852
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(NCC(F)(F)F)N=CC2=CN(C3=CC=C(OC)C=C3)C(=O)C(C3=CC=C(Br)C=C3)=C2N=1
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| InChi Key |
QHXQQFITXAUNPR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H16BrF3N4O2/c1-32-17-8-6-16(7-9-17)30-11-14-10-27-21(28-12-22(24,25)26)29-19(14)18(20(30)31)13-2-4-15(23)5-3-13/h2-11H,12H2,1H3,(H,28,29)
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| Chemical Name |
8-(4-bromophenyl)-6-(4-methoxyphenyl)-2-(2,2,2-trifluoroethylamino)pyrido[4,3-d]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 : ~83.33 mg/mL (~164.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.12 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9791 mL | 9.8953 mL | 19.7906 mL | |
| 5 mM | 0.3958 mL | 1.9791 mL | 3.9581 mL | |
| 10 mM | 0.1979 mL | 0.9895 mL | 1.9791 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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