AG-270

Research use only, not for human use.

AG-270 is an allosteric and orally active inhibitor of MAT2A.

AG-270 is an allosteric and orally active inhibitor of MAT2A.(In Vitro):AG-270 exhibits an IC50 of 20 nM in HCT116 MTAP-null cell SAM at 72 h.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 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).

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. Animal Model:Pancreatic KP4 MTAP-null xenograft mouse model.Dosage:10-200 mg/kg.Administration:Orally, q.d. for 38 days.Result:Led to dose-dependent reductions in tumor SAM levels and tumor growth of KP4 MTAP-null xenografts (TGI = 36% (10 mg/kg), 48% (30 mg/kg), 66% (100 mg/kg), 67% (200 mg/kg).

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Others

Other Targets

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2201056-66-6

489.57

C30H27N5O2

>98% (HPLC)

In Vitro:?DMSO : 4 mg/mL (8.17 mM)

COc(cc1)ccc1C(C(n1nc2-c3ccccc3)=O)=C(Nc3ncccc3)Nc1c2C1=CCCCC1

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(-20℃)

With Ice Pack

≥ 2 years