AG-270 

AG-270 is an allosteric, noncompetitive, first-in-class, reversible and orally active MAT2A inhibitor, with an IC₅₀ of 14 nM^[1].

IC50: 14 nM (MAT2A)^[1].

AG-270 demonstrates potent reduction in levels of intracellular SAM, as well as MTAP-null–selective antiproliferative activity in the HCT116 MTAP isogenic cell model in vitro^[1].
AG-270 exhibits an IC₅₀ of 20 nM in HCT116 MTAP-null cell SAM at 72 h^[1].
MAT2A is a key enzyme in the methionine salvage pathway, responsible for generating the universal methyl donor, S-adenosylmethionine (SAM)^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

AG-270 shows excellent microsomal, hepatocyte, and in vivo metabolic stability across species (human, mouse, rat, dog, and monkey). AG-270 exhibits T1/2 values of 5.9 h, 4.2 h, 4.8 h and 21.3 h in mouse, rat, monkey and dog, respectively^[1].
AG-270 (200 mg/kg, orally, q.d. for 38 days) results in dose-dependent reduction in tumor SAM levels and tumor growth of KP4 MTAP-null xenografts and is well tolerated, with mean body weight loss <5%^[1].
Combining AG-270 with taxanes and gemcitabine yielded additive-tosynergistic antitumor activity, with the docetaxel combination yielding 50% complete tumor regressions in select models; combination benefits are observed in PDX models derived from esophageal, NSCLC, and pancreatic cancers^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

489.57

C₃₀H₂₇N₅O₂

2201056-66-6

Solid

White to off-white

O=C1C(C2=CC=C(OC)C=C2)=C(NC3=NC=CC=C3)NC4=C(C5=CCCCC5)C(C6=CC=CC=C6)=NN14

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

• [1]. Zenon Konteatis, et al. Discovery of AG-270, a First-in-Class Oral MAT2A Inhibitor for the Treatment of Tumors with Homozygous MTAP Deletion. J Med Chem. 2021 Apr 8.  [Content Brief]

  [2]. Marc L Hyer, et al. The MAT2A inhibitor AG-270 combines with both taxanes and gemcitabine to yield enhanced antitumor activity in patient-derived xenograft models.