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    InvivoChem Cat #: V4443
    CAS #: 1020315-31-4 Purity ≥98%

    Description: PF-04457845 is a novel, highly potent and selective FAAH (fatty acid amide hydrolase) inhibitor with IC50 values of 7.2±0.63 nM and 7.4±0.62 nM for hFAAH and rFAAH, respectively. Pharmacological blockade of FAAH has emerged as a potentially attractive strategy for augmenting endocannabinoid signaling and retaining the beneficial effects of cannabinoid receptor activation, while avoiding the undesirable side effects, such as weight gain and impairments in cognition and motor control, observed with direct cannabinoid receptor 1 agonists. PF-04457845 inhibits human FAAH with high potency (k(inact)/K(i) = 40,300 M(-1)s(-1); IC(50) = 7.2 nM) and is exquisitely selective in vivo as determined by activity-based protein profiling. Oral administration of PF-04457845 produced potent antinociceptive effects in both inflammatory [complete Freund's adjuvant (CFA)] and noninflammatory (monosodium iodoacetate) pain models in rats, with a minimum effective dose of 0.1 mg/kg (CFA model). PF-04457845 displayed a long duration of action as a single oral administration at 1 mg/kg showed in vivo efficacy for 24 h with a concomitant near-complete inhibition of FAAH activity and maximal sustained elevation of anandamide in brain. Significantly, PF-04457845-treated mice at 10 mg/kg elicited no effect in motility, catalepsy, and body temperature. Based on its exceptional selectivity and in vivo efficacy, combined with long duration of action and optimal pharmacokinetic properties, PF-04457845 is a clinical candidate for the treatment of pain and other nervous system disorders.

    References:  2011 Jul;338(1):114-24; J Med Chem. 2018 May 24;61(10):4476-4504.

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    Name: PF-04457845
    CAS#: 1020315-31-4
    Chemical Formula: C23H20F3N5O2
    Exact Mass: 455.15691
    Molecular Weight: 455.44121
    Elemental Analysis: C, 60.66; H, 4.43; F, 12.51; N, 15.38; O, 7.03
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Technical InformationSynonym: PF-04457845; PF 04457845; PF04457845; PF-4457845; PF 4457845; PF4457845.
    Chemical Name: N-pyridazin-3-yl-4-[(3-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl)methylidene]piperidine-1-carboxamide
    InChi Code: InChI=1S/C23H20F3N5O2/c24-23(25,26)18-6-7-21(27-15-18)33-19-4-1-3-17(14-19)13-16-8-11-31(12-9-16)22(32)29-20-5-2-10-28-30-20/h1-7,10,13-15H,8-9,11-12H2,(H,29,30,32)
    SMILES Code: O=C(N1CC/C(CC1)=C\C2=CC=CC(OC3=NC=C(C(F)(F)F)C=C3)=C2)NC4=NN=CC=C4

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    Selectivity profiling of PF-04457845 and URB597 by competitive ABPP.   2011 Jul;338(1):114-24.


    Assessment of in vivo protein targets of alkyne analogs of PF-04457845 and URB597 by CC-ABPP.   2011 Jul;338(1):114-24.


    Antihyperalgesic effects of PF-04457845 in the CFA model of inflammatory pain in rats.  2011 Jul;338(1):114-24.


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