PF-04136309

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.

1341224-83-6

INCB8761 | PF-4136309 | PF4136309

>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

C29H31F3N6O3

568.59

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.