1341224-83-6
![1341224-83-6 结构式](/CAS/20200611/GIF/1341224-83-6.gif)
基本信息
EOS-61910
NCB8761(PF-4136309)
INCB8761(PF-4136309)
PF-04136309(INCB-8761)
ZNSVOHSYDRPBGI-LXWOLXCRSA-N
N-(2-((S)-3-(((1R,4S)-4-HYDROXY-4-(5-(PYRIMIDIN-2-YL)
INCB8761
PF-4136309
PF4136309
PF 4136309
INCB-8761
N-(2-((S)-3-(((1r,4S)-4-hydroxy-4-(5-(pyrimidin-2-yl) yridine-2-yl)cyclohexyl)amino)pyrrolidin-1-yl)-2-oxoethyl)-3-(trifluoromethyl)benzamide
Benzamide, N-[2-[(3S)-3-[[trans-4-hydroxy-4-[5-(2-pyrimidinyl)-2-pyridinyl]cyclohexyl]amino]-1-pyrrolidinyl]-2-oxoethyl]-3-(trifluoromethyl)-
物理化学性质
常见问题列表
Human CCR2 5.2 nM (IC 50 ) |
Mouse CCR2 13 nM (IC 50 ) |
Rat CCR2 17 nM (IC 50 ) |
PF-4136309 is potent in human chemotaxis activity (IC 50 =3.9 nM) and in the whole blood assay (IC 50 =19 nM), with IC 50 of 16 and 2.8 nM in mouse and rat chemotaxis assays. PF-4136309 is potent in inhibiting CCR2 mediated signaling events such as intracellular calcium mobilization and ERK (extracellular signal-regulated kinase) phosphorylation with IC 50 values of 3.3 and 0.5 nM, respectively. In hERG patch clamp assay, PF-4136309 inhibits hERG potassium current with an IC 50 of 20 μM. PF-4136309 is not a cytochrome P450 (CYP) inhibitor, with IC 50 values of >30 μM against five major CYP isozymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Moreover, PF-4136309 is not a CYP inducer at concentrations up to 30 μM.
PF-4136309 (2 mg/kg) exhibits a moderate half-life in both species after iv administration (2.5 and 2.4 h). When administered orally, PF-4136309 (10 mg/kg) is absorbed rapidly, with peak concentration time (T max ) at 1.2 h for rats and 0.25 h for dogs. A similar half-life is observed in both species between iv dosing and po dosing. PF-4136309 is well absorbed, with an oral bioavailability of 78% in both species.