PF-06372865 是一种具有口服活性的，α2/α3/α5 亚型选择性的 GABA_A 正向变构调节剂 (PAM)。PF-06372865 是 α1/α2/α3/α5 亚基的高亲和力配体，对 α2，α1 PAM，α2 PAM 的 K_i 值分别为 2.9 nM，21 nM，134 nM，对 α4/α6 亚基的亲和力低。PF-06372865 可以透过血脑屏障 (BBB)。PF-06372865 具有抗焦虑活性，并且有用于癫痫研究的潜力。

PF-06372865 is an orally active, α2/α3/α5 subtype-selective GABA A positive allosteric modulator (PAM). PF-06372865 is a high affinity ligand at GABA A receptors containing α1/α2/α3/α5 subunits (K i s of 2.9 nM, 21 nM, 134 nM for α2, α1 PAM, α2 PAM, respectively), with low affinity for α4/α6 subunits. PF-06372865 can across the blood-brain barrier (BBB). PF-06372865 has anxiolytic activity and has the potential for epilepsy.

Solid

Ki: 2.9 nM (α2), 21 nM (α1 PAM) and 134 nM (α2 PAM)

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.
has not independently confirmed the accuracy of these methods. They are for reference only.

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 T 1/2 of 1.1 hours, a Cl p of 22 mL/min/kg, and a V ss of 2.1 L/kg for rats.
PF-06372865 has a T 1/2 of 0.9 hours, a Cl p of 29 mL/min/kg, and a V ss of 3.4 L/kg for dogs.
has not independently confirmed the accuracy of these methods.

Room temperature in continental US; may vary elsewhere.

4°C, protect from light In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

[1]. Owen RM, et al. Design and Identification of a Novel, Functionally Subtype Selective GABAA Positive Allosteric Modulator (PF-06372865). J Med Chem. 2019 Jun 27;62(12):5773-5796.

In Vitro: DMSO : 50 mg/mL (113.51 mM; Need ultrasonic)配制储备液