AG-270 |
Catalog No.GC62413
One-Click Copy Product Info
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AG-270 is a potent, orally active, allosteric inhibitor of methionine adenosyltransferase 2A (MAT2A) with an IC50 of 14nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2201056-66-6
Sample solution is provided at 25 µL, 10mM.
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AG-270 is a potent, orally active, allosteric inhibitor of methionine adenosyltransferase 2A (MAT2A) with an IC50 of 14nM [1,2]. MAT2A is a cytoplasmic enzyme. The enzyme has been identified as a synthetic lethal target in cancers that the methylthioadenosine phosphorylase (MTAP) gene was deleted [3]. AG-270 can induce synthetic lethality and prevent proliferation of MTAP-deleted cancer cells. AG-270 is also applied in the fields of immune system diseases, hematologic and lymphatic system diseases.
In vitro, AG-270 not only reduces intracellular S-adenosylmethionine (SAM) levels in a concentration-dependent manner (IC50 = 20nM), but also selectively inhibits the proliferation of MTAP-deficient HCT116 cells following a 72‑hour treatment [1]. Treatment of AG-270 alone (0.5–4μM, for 48–72 hours) can slightly induce apoptosis of non-small cell lung cancer cells and inhibit their colony formation. AG 270 combined with the methyltransferase like 3 (METTL3) inhibitor STM2457 exhibited a marked synergistic anti tumor effect [4].
In KP4 MTAP-null pancreatic xenografts, oral AG-270 dose-dependently lowered tumor SAM and yielded 67% tumor growth inhibition (TGI) with <5% weight loss, which indicated good tolerability [1].
References:
[1]. Konteatis, Z., et al., Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous MTAP Deletion. Journal of Medicinal Chemistry, 2021. 64(8): p. 4430-4449.
[2]. Hyer, M.L., et al., The MAT2A inhibitor, AG-270, combines with both taxanes and gemcitabine to yield enhanced anti-tumor activity in patient-derived xenograft models. Cancer Research, 2020. 80(16_Supplement): p. 3090-3090.
[3]. Kalev, P., et al., MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage. Cancer Cell, 2021. 39(2): p. 209-224.e11.
[4]. Xuan, Y.F., et al., The combination of methionine adenosyltransferase 2A inhibitor and methyltransferase like 3 inhibitor promotes apoptosis of non-small cell lung cancer cells and produces synergistic anti-tumor activity. Biochem Biophys Res Commun, 2024. 716: p. 150011.
| Cell experiment [1,2]: | |
Cell lines | HCT-116 and HCT-116 MTAP null cell |
Preparation Method | HCT116 WT and MTAP-/- cells were plated in 96 well tissue culture plates at 20,000 cells per well and allowed to attach overnight at 37°C in 5% CO2. Cells were incubated with AG-270 for 72 hours. After this treatment period, medium was removed and cells were extracted for SAM metabolite measurement by LC-MS/MS. In parallel, both cells were plated at 2,000 cells/well and treated as described above for 96 hours in a cell growth assay. Readout of cell proliferation was obtained by measuring total cellular adenosine triphosphate levels. |
Reaction Conditions | 20, 6.67, 2.22, 0.74, 0.247, 0.082, 0.027, 0.009, 0.003μM; 72 and 96h |
Applications | The SAM levels in HCT116 MTAP-/- cells decreased with increasing concentration after treatment with AG-270 for 72 hours. The growth of MTAP-deficient cells was significantly inhibited (growth percentage dropped from about 100% to about 40%), while WT cells still grew close to 100% at high concentrations after 96 hours of treatment. |
| Animal experiment [1]: | |
Animal models | KP4 MTAP-null xenograft mouse |
Preparation Method | To evaluate the dose-dependent effect of AG-270 in the KP4 xenograft mouse model, KP4 (MTAP‑null human pancreatic cancer cells) were subcutaneously implanted into immunodeficient mice. 60 total animals were randomized into five dose groups (including a control group). AG-270 was administered orally once daily at doses ranging from 10 to 200mg/kg from days 24 to 38. Within 24 hours after the final 200mg/kg dose, tumor samples were collected for pharmacokinetic analysis and SAM level measurement. Tumor volume was monitored regularly to calculate TGI, and body weight was recorded to assess tolerability. |
Dosage form | 10、30、100、200mg/kg; Orally, q.d. for 24-38 days. |
Applications | Treatment with AG-270 resulted in dose-dependent reductions in both tumor SAM levels and tumor growth in KP4 MTAP-null xenografts, with TGI values of 36% at 10mg/kg, 48% at 30mg/kg, 66% at 100mg/kg, and 67% at 200 mg/kg. |
References: | |
| Cas No. | 2201056-66-6 | SDF | |
| Formula | C30H27N5O2 | M.Wt | 489.57 |
| Solubility | DMSO : 170 mg/mL (347.24 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0426 mL | 10.213 mL | 20.4261 mL |
| 5 mM | 408.5 μL | 2.0426 mL | 4.0852 mL |
| 10 mM | 204.3 μL | 1.0213 mL | 2.0426 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 13 reference(s) in Google Scholar.)