PF-3845

Protein target name:

FAAH

Mechanism of action:

Covalent Inhibitor

Recommended Concentration for use in cells:

up to 1 uM

Probe Availability

Probe Information

Target and Probe Information

Target Details

Target class:

Lipid metabolism

Subclass:

Serine Hydrolase

HUGO ID:

HGNC:3553

Entrez gene ID:

2166

UNIPROT ID:

O00519

Target alias:

FAAH-1, PSAB

Probe Details

Chemical Probes Portal ID:

CPP735

Probe alias:

PF3845, PF 3845, cpd 10, PIX

PubChem CID:

25154867

ChEMBL ID:

CHEMBL1651524

SMILES string:

C1CN(CCC1CC2=CC(=CC=C2)OC3=NC=C(C=C3)C(F)(F)F)C(=O)NC4=CN=CC=C4

InChi Key:

NBOJHRYUGLRASX-UHFFFAOYSA-N

Orthogonal probe:

PF-04457845

Physico-chemical properties

NMR:

1H NMR (400 MHz, CDCl3) δ ppm 1.19 - 1.37, (m, 2 H), 1.70 - 1.86 (m, 3 H), 2.60 (d, J=6.68 Hz, 2 H), 2.86 (td, J=12.92, 2.30 Hz, 2 H), 4.09 (ddd, J=13.40, 2.14, 2.02 Hz, 2 H), 6.63 (br. s., 1 H), 6.94 (t, J=1.91 Hz, 1 H), 6.97 - 7.02 (m, 2 H), 7.02 - 7.07 (m, 1 H), 7.24 (dd, J=8.36, 4.65 Hz, 1 H), 7.35 (t, J=7.82 Hz, 1 H), 7.89 (ddd, 1 H), 8.05 (ddd, J=8.40, 2.53, 1.43 Hz, 1 H), 8.24 (dd, J=4.68, 1.12 Hz, 1 H), 8.44 (td, J=1.67, 0.83 Hz, 1 H), 8.48 (d, J=2.29 Hz, 1 H);

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

Kinact, Ki

3.3, 230 nM

Potency assay:

enzyme-coupled assay with oleamide as a substrate

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

2WAP3LJ6

Structure-activity relationship:

yes

In cell validation

On target activity in cells

Potency in cells:

IC50

18 nM

Potency assay (cells):

TLC of radio-labelled fatty acid conversions

Off target activity in cells

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

In vivo validation

Organism:

MouseRat

Dose:

10 mg/Kg IP1-30 mg/Kg PO

Route of delivery:

Oral

Other route of delivery:

Organ of Interest

Organ (O):

Brain

Primary Reference

Reference (doi):

10.1016/j.chembiol.2009.02.013

Reference (PMID):

PMC2692831

Under Review

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

SAB Rating

Rating for use in Cells

1 review(s)

Rating for use in Model Organisms

1 review(s)

SAB Members

SAB 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.

Jun 4 2021 - 11:55am

PF-3845

Probe Availability

Probe Information

Target Details

FAAH-1, PSAB

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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PF-3845

Probe Availability

Probe Information

Target Details

FAAH-1, PSAB

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?