PF-04136309

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

PF-4136309 (INCB8761) 是一种有效、选择性、竞争性、可逆的完全 CCR2 拮抗剂，IC50 为 2-5 nM。

PF-4136309 (INCB8761) is a potent, selective, competitive, reversible full CCR2 antagonist with IC50 of 2-5 nM; depletes inflammatory monocytes and macrophages from the primary tumor and premetastatic liver resulting in enhanced antitumor immunity, decreased tumor growth, and reduced metastasis.Pancreatic Cancer Phase 2 Clinical(In Vitro):PF-4136309 is potent in human chemotaxis activity (IC50=3.9 nM) and in the whole blood assay (IC50=19 nM), with IC50 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 IC50 values of 3.3 and 0.5 nM, respectively. In hERG patch clamp assay, PF-4136309 inhibits hERG potassium current with an IC50 of 20 μM. PF-4136309 is not a cytochrome P450 (CYP) inhibitor, with IC50 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.(In Vivo):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 (Tmax) 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.

PF-4136309 is potent in human chemotaxis activity (IC50=3.9 nM) and in the whole blood assay (IC50=19 nM), with IC50 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 IC50 values of 3.3 and 0.5 nM, respectively. In hERG patch clamp assay, PF-4136309 inhibits hERG potassium current with an IC50 of 20 μM. PF-4136309 is not a cytochrome P450 (CYP) inhibitor, with IC50 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 (Tmax) 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.

INCB8761 | PF-4136309 | PF4136309

GPCR/G Protein

Chemokine Receptor

CCR2

Cancer

Pancreatic Cancer

1341224-83-6

568.59

C29H31F3N6O3

>98% (HPLC)

DMSO: ≥32 mg/mL （ < 1 mg/ml refers to the product slightly soluble or insoluble )

O=C(NCC(N1C[C@@H](NC2CCC(C3=NC=C(C4=NC=CC=N4)C=C3)(O)CC2)CC1)=O)C5=CC=CC(C(F)(F)F)=C5

(S)-N-(2-(3-((4-hydroxy-4-(5-(pyrimidin-2-yl)pyridin-2-yl)cyclohexyl)amino)pyrrolidin-1-yl)-2-oxoethyl)-3-(trifluoromethyl)benzamide

(-20℃)

With Ice Pack

≥ 2 years