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PF-05105679 | PF-05105679 : Antagonist of TRPM8
RATINGS:
Cellular Use: (1 reviews)

In Model Organisms: (1 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
TRPM8
  • IC50:181 nM
  • IC50:103 ± 29 nM
  • IC50:13.8 ± 2.2 nM
Antagonist
up to 1 uM

Selectivity

In Vitro Selectivity Assessment
Selectivity Assessment Description:
Selectivity within target family: Selective over related family at 10 µM: TRPV1, TRPA1 (Ca+ mobiliza ...
In Vitro Selectivity Assessment
Selectivity Assessment Description:
Clean Kinase panel at 1 uM

Potency
Cellular
In Vitro

TRPM8

Mode of Action: Antagonist

Structure-Activity-Relationship data available? No

DOI Reference: 10.1021/ml500479v

In Vivo Validations

Rat
Dose: 2-10 mg/Kg
Route of delivery: Intravenous
Plasma half life: 3.6 h
Systemic clearance: 19.8 mL/min/Kg
Fb : 98.8%
Bioavailability: 29 (2 mg/Kg) and 62% (10 mg/Kg)
Volume of Distribution at Steady-State: 6.2 L/Kg

DOI Reference: 10.1021/ml500479v

Dog
Dose: 20 mg/Kg
Route of delivery: Intravenous
Plasma half life: 3.9 h
Systemic clearance: 31 mL/min/Kg
Fb : 96.7%
Bioavailability: 92 %
Volume of Distribution at Steady-State: 7.4 L/Kg

DOI Reference: 10.1021/ml500479v

Negative Control Compounds

PF-05257137
Notes: PF-05257137 with IC50 > 10 µM;Clean GPCR scan

Chemical Information

Molecular Formula C26H21FN2O3
SMILEs C[C@H](c1ccc(F)cc1)N(Cc1cccc(C(=O)O)c1)C(=O)c1cnc2ccccc2c1
InChI InChI=1S/C26H21FN2O3/c1-17(19-9-11-23(27)12-10-19)29(16-18-5-4-7-21(13-18)26(31)32)25(30)22-14-20-6-2-3-8-24(20)28-15-22/h2-15,17H,16H2,1H3,(H,31,32)/t17-/m1/s1
Molecular weight 428.15 Da
AlogP 0.0
HBond acceptors 5
HBond donors 1
Atoms 53

Vendors

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Expert Reviews

by SERP
(on 28 Jan 2022)
Cellular Use Rating
In Model Organisms
Good probe which progressed to clinical trials. Good to also have a control molecule but would also expect data on the distomer (inactive enantiomer) as a control. Efficacy from oral dosing would also...
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