PF-05198007

Names

[ Name ]:
PF-05198007

Biological Activity

[Description]:

PF-05198007 is a potent, state-dependent, subtype selective Nav1.7 inhibitor with IC50 of 9 nM, no significant activity against Nav1.5 (IC50>10 uM); increases action potential rheobase in small diameter mDRG neurons, demonstrates in vivo efficacy in a mouse capsaicin-induced neurogenic flare model.

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Neurological Disease

[Target]

Nav1.7[1].

[In Vitro]

PF-05198007 (30 nM) blocks on average 83.0 ± 2.7% of the total TTX-S current indicating that the major TTX-S conductance is carried through Nav1.7 channels in small-diameter mouse DRG neurons (n = 35)[1].

[In Vivo]

PF-05198007 (1 or 10 mg/kg, orally) reduces the capsaicin flare response in WT, but not Nav1.7Nav1.8Cre mice[1]. Animal Model: Adult Male C57Bl/6J Wild type (WT) and Nav1.7Nav1.8Cre mice[1]. Dosage: 1 or 10 mg/kg. Administration: Orally once. Result: Reduced the flare response to capsaicin for the duration of the observation period (55 mins; Vehicle; 4930 ± 751 versus 1 and 10 mg/kg 1967 ± 472 and 2265 ± 382, respectively (n = 7), AUC, p < 0.05).

[References]

[1]. Alexandrou AJ, et al. Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release. PLoS One. 2016 Apr 6;11(4):e0152405.

[2]. Kushnarev M, et al. Neuropathic pain: preclinical and early clinical progress with voltage-gated sodium channel blockers. Expert Opin Investig Drugs. 2020 Mar;29(3):259-271.

Chemical & Physical Properties

[ Molecular Formula ]:
C₁₉H₁₂ClF₄N₅O₃S₂

[ Molecular Weight ]:
533.901

Related Compounds

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