Identification | Back Directory | [Name]
CFI-402257 HCl | [CAS]
1610677-37-6 | [Synonyms]
CFI-402257 HCl CFI-402257 hydrochloride N-cyclopropyl-4-(7-((((1s,3s)-3-hydroxy-3-methylcyclobutyl)methyl)amino)-5-(pyridin-3-yloxy)pyrazolo[1,5-a]pyrimidin-3-yl)-2-methylbenzamide hydrochloride | [Molecular Formula]
C28H31ClN6O3 | [MOL File]
1610677-37-6.mol | [Molecular Weight]
535.05 |
Hazard Information | Back Directory | [Uses]
CFI-402257 hydrochloride is a highly selective and orally bioavailable TTK/Mps1 inhibitor with an IC50 of 1.7 nM for TTK in vitro. CFI-402257 hydrochloride has anti-cancer activity[1]. | [in vivo]
CFI-402257 given orally QD shows dose-dependent activity in mice with established tumors from xenografted MDA-MB-231 human TNBC cells and MDA-MB-468 human TNBC cells in mice. CFI-402257 demonstrates antitumor activity in a platinum-resistant PDX model of high-grade serous ovarian cancer[2].
Animal Model: | Xenografted MDA-MB-231 human TNBC cells and MDA-MB-468 human TNBC cells in mice[2]. | Dosage: | 5, 6 mg/kg. | Administration: | Oral gavage, daily. | Result: | Xenografted MDA-MB-231 human TNBC cells: 5 mg/kg, tumor growth inhibition (TGI) = 74%; 6 mg/kg, TGI = 89%.
Xenografted MDA-MB-468 human TNBC cells: 5 mg/kg, tumor growth inhibition (TGI) = 75%; 6 mg/kg, TGI = 94%.
|
Animal Model: | PDX model of high-grade serous ovarian cancer[2]. | Dosage: | 6.5, 7.5 mg/kg. | Administration: | Oral gavage, daily. | Result: | 6.5 mg/kg, tumor growth inhibition (TGI) = 61%; 7.5 mg/kg, TGI = 97%.
|
| [References]
[1] Liu Y, et al. Discovery of Pyrazolo[1,5-a]pyrimidine TTK Inhibitors: CFI-402257 is a Potent, Selective, Bioavailable Anticancer Agent. ACS Med Chem Lett. 2016 May 6;7(7):671-5. DOI:10.1021/acsmedchemlett.5b00485 [2] Mason JM, et al. Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3127-3132. DOI:10.1073/pnas.1700234114 |
|
|