PF-06372865

Research use only, not for human use.

PF-06372865 is a novel potent, α2/3 functionally selective GABAA receptor positive allosteric modulator.

PF-06372865 is a novel potent, α2/3 functionally selective GABAA receptor positive allosteric modulator; exhibits functional selectivity for receptors containing α2/3/5 subunits, with significant positive allosteric modulation (90-140%) but negligible activity (<20%) at GABAA receptors containing α1 subunits; demonstrates a robust increase in saccadic peak velocity, increases in beta frequency qEEG and a slight saturating increase in body sway in clinical trials.Epilepsy Phase 1 Clinical.

PF-06372865 (compound 34) has Ki values of 0.18 nM, 2.9 nM, 1.1 nM, 18 nM for human GABAA α1β3γ2, α2β2γ2, α3β3γ2, α5β2γ2 and 0.34 nM, 4.58 nM for rat GABAA α1β3γ2, α2β2γ2.

PF-06372865 (compound 34; 3, 10 mg/kg; orally; single dose) significantly increases the paw withdrawal threshold (PWT) in chronic constriction injury (CCI) animals. PF-06372865 (0.3, 3, 10 mg/kg for mouse and 1, 3, 10 mg/kg for rat; orally) exhibits efficacy in two models of epilepsy, PTZ induced seizures (mouse), and amygdala kindling (rat). PF-06372865 (0.1, 0.32, 1, 3.2 and 10 mg/kg; orally) has anxiolytic activity at 3.2 and 10 mg/kg in elevated plus maze (male C57Bl/6 mice). PF-06372865 has a T1/2 of 1.1 hours, a Clp of 22 mL/min/kg, and a Vss of 2.1 L/kg for rats. PF-06372865 has a T1/2 of 0.9 hours, a Clp of 29 mL/min/kg, and a Vss of 3.4 L/kg for dogs. Animal Model:Chronic constriction injury (CCI) model (male Wistar rats)Dosage:3, 10 mg/kg Administration:Orally Result:Significantly increased paw withdrawal latency.

PF06372865

Membrane Transporter/Ion Channel

GAT

GAT

Neurological Disease

Epilepsy

1614245-70-3

440.493

C22H21FN4O3S

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (113.51 mM)

COC1=CC(S(=O)(CC)=O)=CC=C1C2=C(F)C=CC(C3=C4C(N(CC)C=N4)=NN=C3)=C2

7-ethyl-4-(4'-(ethylsulfonyl)-6-fluoro-2'-methoxybiphenyl-3-yl)-7H-imidazo[4,5-c]pyridazine

(-20℃)

With Ice Pack

≥ 2 years