PF-05105679

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-05105679 是一种有效的选择性 TRPM8 通道抑制剂，IC50 为 103 nM（人 TRPM8 电流抑制）。

PF-05105679 is a potent, selective TRPM8 channel inhibitor with IC50 of 103 nM (human TRPM8 currents inhibition); displays >100-fold selectivity against a broad panel of 90 receptors, ion channels, and enzymes; demonstrates moderately potency against agonist (WS-12) and cold modalities of activation of TRPM8 in plate-based assay formats with IC50 of 181 and 480 nM, respectively, shows increased potency on voltage activation in HEK-293 cells at 12°C with IC50 of 13.8 nM; demonstrates activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduces core body temperature in the rats, and reduces pain in the cold pressor test in humans.Pain Phase 1 Clinical.

PF-05105679 demonstrates >100-fold selectivity across a range of different receptors, ion channels, and enzymes including the closely related TRPV1 and TRPA1 channels. TRPM8, also known as the cold and menthol receptor 1 (CMR1), is a member of the melastatin subfamily.

PF-05105679 (0.2 mg/kg for iv and 20mg/kg for oral gavage) has a T1/2 of 3.9 hours, a CL of 31 mL/min/kg, and a Vss of 7.4 L/kg for dogs. PF-05105679 (2, 20 mg/kg) has a T1/2 of 3.6 hours, a CL of 19.8 mL/min/kg, and a Vss of 6.2 L/kg for rats. Animal Model:Male beagle dogs (weight 10 to 15kg) Dosage:0.2 mg/kg (iv) or 20 mg/kg (oral gavage)(Pharmacokinetic Analysis) Administration:Iv or oral gavageResult:Had a T1/2 of 3.9 hours, a CL of 31 mL/min/kg, and a Vss of 7.4 L/kg for dogs.

PF 05105679 | PF05105679

Membrane Transporter/Ion Channel

TRP/TRPV Channel

TRP/TRPV Channel

Neurological Disease

Pain

1398583-31-7

428.463

C26H21FN2O3

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (291.75 mM)

O=C(O)C1=CC=CC(CN([C@@H](C2=CC=C(F)C=C2)C)C(C3=CC4=CC=CC=C4N=C3)=O)=C1

(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid

(-20℃)

With Ice Pack

≥ 2 years