| Identification | Back Directory | [Name]
Pyrazolo[1,5-a]pyrimidin-7(4H)-one, 3-(1-cyclohexen-1-yl)-6-(4-methoxyphenyl)-2-phenyl-5-(2-pyridinylamino)- | [CAS]
2201056-66-6 | [Synonyms]
Pyrazolo[1,5-a]pyrimidin-7(4H)-one, 3-(1-cyclohexen-1-yl)-6-(4-methoxyphenyl)-2-phenyl-5-(2-pyridinylamino)- | [Molecular Formula]
C30H27N5O2 | [MDL Number]
MFCD34368529 | [MOL File]
2201056-66-6.mol | [Molecular Weight]
489.57 |
| Chemical Properties | Back Directory | [Boiling point ]
709.3±70.0 °C(Predicted) | [density ]
1.30±0.1 g/cm3(Predicted) | [solubility ]
DMSO: Slightly soluble | [form ]
A solid | [pka]
7.30±0.10(Predicted) | [color ]
White to off-white | [InChIKey]
HSVRUECLQUGTDS-UHFFFAOYSA-N | [SMILES]
C12=C(C3CCCCC=3)C(C3=CC=CC=C3)=NN1C(=O)C(C1=CC=C(OC)C=C1)=C(NC1=NC=CC=C1)N2 |
| Hazard Information | Back Directory | [Uses]
AG-270 is an allosteric, noncompetitive, first-in-class, reversible and orally active MAT2A inhibitor, with an IC50 of 14 nM[1]. | [in vivo]
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].
| Animal Model: | Pancreatic KP4 MTAP-null xenograft mouse model[1].
| | 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). |
| [References]
[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. DOI:10.1021/acs.jmedchem.0c01895
[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. |
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