AG-270 是非竞争性的、首创的、可逆的、具有口服活性的 MAT2A 变构抑制剂，其 IC₅₀ 值为 14 nM。

AG-270 is an allosteric, noncompetitive, first-in-class, reversible and orally active MAT2A inhibitor, with an IC 50 of 14 nM.

Solid

IC50: 14 nM (MAT2A).

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 .
AG-270 exhibits an IC50 of 20 nM in HCT116 MTAP-null cell SAM at 72 h.
MAT2A is a key enzyme in the methionine salvage pathway, responsible for generating the universal methyl donor, S-adenosylmethionine (SAM).
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.
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%.
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.
has not independently confirmed the accuracy of these methods.

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[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.
[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.

In Vitro: DMSO : 4 mg/mL (8.17 mM; ultrasonic and warming and heat to 60°C)配制储备液