INCB8761(PF-4136309)
Names
Biological Activity
[Description]:
PF-4136309 is a potent, selective, and orally bioavailable CCR2 antagonist, with IC50 of 5.2 nM, 17 nM and 13 nM for human, mouse and rat CCR2.
[Related Catalog]:
[Target]
Human CCR2:5.2 nM (IC50)
Mouse CCR2:13 nM (IC50)
Rat CCR2:17 nM (IC50)
[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[1].
[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[1].
[References]
[Related Small Molecules]
INCB3344
|
Cenicriviroc
|
RS504393
|
RS-102895 hydrochloride
|
BX 471
|
TAK-779
|
Vercirnon
|
MK-0812 Succinate
|
AZD 2098
|
CCX140
|
INCB 3284
|
ZK 756326
|
CCR2-RA-[R]
|
BMS-813160
|
(D-Ala1)-Peptide T amide
Chemical & Physical Properties
[ Molecular Formula ]:
C29H31F3N6O3
[ Molecular Weight ]:
568.59000
[ Exact Mass ]:
568.24100
[ PSA ]:
120.34000
[ LogP ]:
4.02780
[ Storage condition ]:
2-8℃