FAAH

FAAH/cPLA2α-IN-1 is a compound that simultaneously inhibits both FAAH and cPLA2α, demonstrating potent activity with half-maximal inhibitory concentrations (

CAY10435, a β-ketooxazapyridine and selective FAAH inhibitor, exhibits antimicrobial properties. It binds non-competitively to the FAAH of Dictyostelium discoideum, demonstrating a Kd value of 0.57 nM [1] [2].

Fatty acid amide hydrolase (FAAH), an enzyme responsible for the hydrolysis and inactivation of fatty acid amides like anandamide and oleamide, has been identified as a target by the potent FAAH inhibitor PHOP. PHOP demonstrates remarkable inhibitory activity with K_i values as low as 0.094 nM for human FAAH and 0.2 nM for rat FAAH. Additionally, through a proteomics assay focusing on the serine hydrolase enzyme family, to which FAAH belongs, PHOP's selectivity was evaluated, presenting IC_50 values of 1.1 nM against FAAH, 1.4 nM against triacylglycerol hydrolase (TGH), and greater than 100 µM against an uncharacterized hydrolase (KIAA1363). This specificity profile of PHOP underscores its potential for yielding precise outcomes in studies involving complex biological systems.

OMDM-5 is a potent vanilloid receptor type 1 (TRPV1, EC50 = 75 nM) agonist, showing weak ligand activity at cannabinoid type 1 receptor (CB1, Ki=4.9 μM).

Irafamdastat (BMS-986368) [Example 74] is an inhibitor of FAAH and MAGL, with IC50 values of ≤ 100 nM for human FAAH and 100 nM-1 μM for human MAGL. It exhibits anticonvulsant properties.

FAAH/MAGL-IN-1 (SIH 3) inhibits FAAH & MAGL with IC50 of 31 & 29 nM, useful in neuropathic pain research.

NRMA-8 is a small-molecule nuclear receptor modulator capable of penetrating the brain. It holds potential for research into central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease, demyelinating diseases, and glioblastoma.

FAAH/MAGL-IN-3 irreversibly inhibits FAAH (IC50: 179 nM) & MAGL (IC50: 759 nM) with low PAMPA permeability.

MK-3168 (12C) functions as a FAAH inhibitor, exhibiting IC50 values of 1.0 nM, 5.5 nM, and 1.7 nM for human, rhesus, and rat respectively. It demonstrates effective brain uptake and FAAH-specific signaling. Additionally, 11 C MK-3168 is applicable as a FAAH PET tracer.

Sob-AM2 is an effective substrate targeting the fatty acid amide hydrolase (FAAH) expressed in the brain, with a Km of 1.3 μM. It delivers higher concentrations of Sobetirome to the central nervous system at minimal peripheral systemic doses, thereby activating the central thyroid hormone receptor β (TRβ).

AZ513 is a reversible FAAH inhibitor, exhibiting an IC50 of 551 nM for human FAAH and 27 nM for rat FAAH. It inhibits the hydrolysis of arachidonoyl ethanolamide in HEK293 cells transfected with human FAAH, with an IC50 of 360 nM.

FAAH/MAGL-IN-2: potent, reversible, oral FAAH & MAGL inhibitor, IC50: 11/36 nM, may research neuropathic pain, no locomotion issue.