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。
货号:ajcx33674
CAS:2201056-66-6
分子式:C30H27N5O2
分子量：489.57
溶解度:DMSO : 170 mg/mL (347.24 mM; Need ultrasonic)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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

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].

[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.