| Identification | Back Directory | [Name]
7H-Pyrrolo[2,3-d]pyrimidine-5-carboxamide, 4-amino-N-[4-(methoxymethyl)phenyl]-7-(1-methylcyclopropyl)-6-[3-(4-morpholinyl)-1-propyn-1-yl]- | [CAS]
2129515-96-2 | [Synonyms]
Vepafestinib
7H-Pyrrolo[2,3-d]pyrimidine-5-carboxamide, 4-amino-N-[4-(methoxymethyl)phenyl]-7-(1-methylcyclopropyl)-6-[3-(4-morpholinyl)-1-propyn-1-yl]- | [Molecular Formula]
C26H30N6O3 | [MOL File]
2129515-96-2.mol | [Molecular Weight]
474.55 |
| Chemical Properties | Back Directory | [Boiling point ]
637.3±55.0 °C(Predicted) | [density ]
1.33±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 50 mg/mL (105.36 mM; Need ultrasonic) | [form ]
Solid | [pka]
11.35±0.70(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
Vepafestinib (TAS0953/HM06) is a next-generation brain-penetrant, selective and orally active RET inhibitor with an IC50 value of 0.33 nM. Vepafestinib inhibits the phosphorylation of RET and its downstream signaling pathways, thus blocking the growth and signal transduction of tumor cells and inducing cell cycle arrest and apoptosis. Vepafestinib can be used in the research of various RET-driven cancers, such as non-small cell lung cancer, thyroid cancer and other disease areas[1]. | [in vivo]
Vepafestinib (12.5-100 mg/kg; oral administration) significantly inhibits tumor growth and has no significant effect on animal body weight in mouse models implanted with NIH-3T3-RET, ECLC5B, LC-2/ad, LUAD-0057AS1, LUAD-0087AS2, LUAD-0077AS1 cells or tumors[1].
Vepafestinib (10-50 mg/kg; oral administration; twice daily; continuous administration) effectively inhibits tumor growth without affecting animal body weight in mouse models of Ba/F3 KIF5B-RETWT or Ba/F3 KIF5B-RETG810R allograft tumors[1]. | Animal Model: | Female athymic nude mice (6-8 weeks old), implanted subcutaneously with NIH-3T3 cells expressing CCDC6-RET fusion complementary DNA[1]. | | Dosage: | 12.5 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg | | Administration: | Oral gavage, once or twice daily, for 7 days | | Result: | Resulted in a dose-dependent decrease in the growth of NIH-3T3-RET xenograft tumors. All dosages tested significantly reduced tumor volume, and there was no statistically significant reduction in animal weight. |
| Animal Model: | Female NOD-SCID gamma (NSG) mice (6-8 weeks old), implanted subcutaneously with ECLC5B xenograft tumors[1] | | Dosage: | 25 mg/kg, 50 mg/kg, 100 mg/kg | | Administration: | Oral gavage, once or twice daily, for 35 days | | Result: | Significantly reduced ECLC5B xenograft tumor growth, and there was no significant reduction in animal weight. |
| Animal Model: | Female NSG mice (6-8 weeks old), implanted subcutaneously with LUAD-0057AS1 patient-derived xenograft (PDX) tumors[1] | | Dosage: | 50 mg/kg, 100 mg/kg | | Administration: | Oral gavage, once or twice daily, for 21 days | | Result: | Significantly reduced the volume of LUAD-0057AS1 PDX tumors, and there was no significant reduction in animal weight. |
| [References]
[1] Miyazaki I, et al. Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations. Nat Cancer. 2023 Sep;4(9):1345-1361. doi: 10.1038/s43018-023-00630-y. Epub 2023 Sep 21. Erratum in: Nat Cancer. 2023 Oct;4(10):1526. DOI:10.1038/s43018-023-00630-y
[2] Vepafestinib: a RET-selective inhibitor with enhanced CNS penetrance targets therapy-resistant mutants. Nat Cancer. 2023 Sep;4(9):1220-1221. DOI:10.1038/s43018-023-00631-x |
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