PF-3845

Covalent Inhibitor of FAAH

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe PF-3845 is in the process of SERP review.

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Information

FAAH

Covalent Inhibitor

up to 1 uM

DOI - 10.1016/j.chembiol.2009.02.013

Probe Availability:

In Vitro Validations

Uniprot ID: O00519

Target Class: Lipid metabolism

Target SubClass: Serine Hydrolase

Potency: Kinact, Ki

Potency Value: Kinact 3.3 nM

Potency Assay: enzyme-coupled assay with oleamide as a substrate

PDB ID for probe-target interaction (3D structure): 2WAP, 3LJ6

Structure-activity relationship: yes

Target aliases:

Fatty-acid amide hydrolase 1, FAAH1, FAAH, FAAH1_H ...

DOI Reference: 10.1016/j.chembiol.2009.02.013

Uniprot ID: O00519

Target Class: Lipid metabolism

Target SubClass: Serine Hydrolase

Potency: Ki

Potency Value: 230 nM

Potency Assay: enzyme-coupled assay with oleamide as a substrate

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Fatty-acid amide hydrolase 1, FAAH1, FAAH, FAAH1_H ...

DOI Reference: 10.1016/j.chembiol.2009.02.013

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Cell:

Negligible activity against FAAH-2 (IC50>10 mM) in COS-7 cells. Profiled in vivo for FP-rhodamine-labeled brain serine hydrolase activities from mice, no observer inhibition

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

There are two human FAAH enzymes (FAAH-1 and FAAH-2) that may collaborate to control Fatty Acid Amide catabolism. There is only a 20% sequence homology between the two enzymes and PF-3845 suffers from an apparent loss of activity against FAAH-2 (IC₅₀>10 μM) in COS-7 cells. Because FAAH-2 can be found in rabbits, this animal may be a more appropriate species to conduct the animal studies. In addition, the development of a probe that has activity against both enzymes would be more relevant as a chemical probe to model the potential therapy in humans. An example would be URB597 which inhibits FAAH-2.

(last updated: 4 Jun 2021 )