PF-04457845 (CAS 1020315-31-4), also known as Redafamdastat, is a highly potent and selective irreversible inhibitor of fatty acid amide hydrolase (FAAH), developed as a non-opioid approach to pain management and CNS disorder research. The compound combines sub-nanomolar target potency with oral bioavailability and a long duration of action, making it a clinically relevant tool for endocannabinoid system studies. Enamine offers PF-04457845 as a high-purity research sample for pharmacological and translational investigations.
PF-04457845 redafamdastat is a urea-based small molecule with molecular formula C₂₃H₂₀F₃N₅O₂ and a molecular weight of 471.43 g/mol. Its architecture features a piperidine-linked phenyl urea core paired with a trifluoromethyl-substituted pyridazine group, engineered to engage the catalytic serine of FAAH covalently. The PF-04457845 SMILES notation — as well as the PF 04457845 SMILES and PF-04457845 redafamdastat SMILES strings — are widely referenced in computational serine hydrolase inhibitor design and virtual selectivity profiling. The compound is registered under CAS 1020315-31-4 and progressed to Phase 2 clinical evaluation for pain and cannabis use disorder.
Application of PF-04457845
As a validated PF-04457845 FAAH inhibitor, Redafamdastat PF-04457845 is applied across pain research, CNS pharmacology, and endocannabinoid biology. Scientists use it to study anandamide elevation and cannabinoid receptor–mediated signaling without the side effects associated with direct CB1 agonists — motor impairment, hypothermia, and catalepsy. PF 04457845 is also employed in cannabis withdrawal models, neuroinflammation studies, and activity-based protein profiling workflows for serine hydrolase selectivity mapping. Its well-defined irreversible mechanism makes it a reference compound in covalent enzyme inhibitor research.
Biochemical and Physiological Actions
Redafamdastat PF-04457845 inactivates FAAH through carbamylation of the catalytic serine residue, producing irreversible enzyme blockade with kinact/Ki of 40,300 M⁻¹s⁻¹ and IC₅₀ values of 7.2 nM and 7.4 nM for human and rat FAAH, respectively. This covalent mechanism confers exceptional selectivity across the broader serine hydrolase superfamily, confirmed by competitive ABPP profiling in vivo. Enzyme inhibition raises tissue levels of anandamide and other fatty acid amides, amplifying endogenous cannabinoid tone without direct receptor activation. A single oral dose of 1 mg/kg in mice achieves near-complete FAAH inhibition sustained over 24 hours, with no measurable effects on motility, body temperature, or catalepsy at 10 mg/kg.
Features and Benefits of PF-04457845
PF-04457845 (Redafamdastat, CAS 1020315-31-4) offers a well-validated pharmacological profile for endocannabinoid and pain research:
- sub-nanomolar FAAH inhibition (IC₅₀ 7.2 nM) via irreversible covalent carbamylation;
- exceptional serine hydrolase selectivity confirmed by competitive ABPP in vivo;
- oral bioavailability with 24-hour duration of action at 1 mg/kg;
- Phase 2 clinical data available across pain and cannabis use disorder indications.
When sourced as EBC-420074, the compound is supplied with analytical quality control data for reproducible use in biochemical and cellular assay workflows.
Powered by Bioz