PF-04457845

Protein target name:

FAAH

Mechanism of action:

Covalent Inhibitor

Recommended Concentration for use in cells:

~~100 nM~~

Reviewer suggested Concentration for use in cells:

40 nM

Probe Availability

MedChemExpress

TOCRIS

Sigma-Aldrich

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

Probe alias:

cpd 23

PubChem CID:

24771824

ChEMBL ID:

CHEMBL1651534

SMILES string:

O=C(NC1=NN=CC=C1)N(CC/2)CCC2=C\C3=CC=CC(OC4=NC=C(C(F)(F)F)C=C4)=C3

InChi Key:

BATCTBJIJJEPHM-UHFFFAOYSA-N

Control compound:

PF-04875474

Orthogonal probe:

PF-3845

Physico-chemical properties

NMR:

1H NMR (400 MHz, CD3OD) δ ppm 2.54 (dt, J=50.71, 5.84 Hz, 4 H) 3.64 (dt, J=36.50, 5.84 Hz, 4 H) 6.47 (s, 1 H) 6.96 - 7.07 (m, 2 H) 7.08 - 7.20 (m, 2 H) 7.40 (td, J=7.72, 0.52 Hz, 1 H) 7.59 (dd, J=9.13, 4.62 Hz, 1 H) 8.08 (dd, J=8.67, 2.68 Hz, 1 H) 8.13 (d, J=8.92 Hz, 1 H) 8.43 (dt, J=1.79, 0.81 Hz, 1 H) 8.79 (d, J=4.19 Hz, 1 H).

13C NMR (101 MHz, CDCl3) δ ppm 29.33, 35.93, 44.77, 45.83, 111.61, 118.86, 119.74, 121.97, 124.83, 126.21, 128.09, 129.80, 136.90, 136.93, 138.06, 139.18, 145.65, 145.69, 147.76, 153.26, 156.81, 165.91.

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

7.2 nM (human), 7.4 nM (Rat)

Potency assay:

glutamate dehydrogenase-coupled FAAH assay

Structure-activity relationship:

yes

Off target activity

Probe Selectivity in Vitro:

Selectivity profiling by competitive ABPP, shows no inhibition of ser. Hydrolases. Selectivity of PF-04457845 against the serine hydrolase superfamily of enzymes (>200 members in humans) @ 10 and 100 uM shows no off-targets. Outside target family: PF-04457845 exhibits a favourable selectivity profile when screened against a 68 target CEREP panel @ 10 uM. Low CYP inhibition IC50 ~10 uM.

In cell validation

On target activity in cells

Potency in cells:

IC50

3.2 nM

Potency assay (cells):

Measurement of FAAH Activity using 3H-labelled substrate

In vivo validation

Organism:

RatDog

Dose:

1 mg/Kg PO0.5 mg/Kg IV

Route of delivery:

OralIntravenous

Plasma half life:

14.3 (R), 35.2 (D) h

Systemic clearance:

3.0 (R), 1.3 (D) mL/min/Kg

Fraction of probe bound to plasma protein:

88 (R), 58 (D) %

Cmax:

256 (R), 240 (D) ng/mL

Tmax:

4 (R), 1 (D) h

Organ of Interest

Organ (O):

Brain

Primary Reference

Reference (doi):

10.1021/ml100190t

Reference (PMID):

21666860

External Resources

Available data:

SGC Chemical Probes

PF-04457845

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

External Resources

Supporting Organizations

Interested in supporting the portal?

Search form

PF-04457845

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

External Resources

Supporting Organizations

Interested in supporting the portal?