Nidufexor | Partial Agonist of NR1H4
RATINGS:
Cellular Use: (1 reviews)

In Model Organisms: (1 reviews)
Control Compounds

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
NR1H4
  • EC50:7 nM
  • EC50:32 nM
Partial Agonist
up to 1 uM

Selectivity

In Cell Selectivity Assessment
Selectivity Assessment Description:
Profiling across a panel of enzymes, ion channels, nuclear receptors, and GPCRs demonstrated the ...

Potency
Cellular
In Vitro

NR1H4

Mode of Action: Partial Agonist

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.9b01621

In Vivo Validations

Mouse, Rat, Dog
Dose: IV: 3 mg/Kg PO: 10 mg/kg (M) IV: 5 mg/kg / PO: 10 mg/kg (R), IV: 0.5 mg/kg / PO: 2 mg/kg (D)
Route of delivery: Intravenous, Oral
Plasma half life: 4.5 (M), 4.4 (R), 6.8 (D)
Systemic clearance: 9.8 (M), 5.6 (R), 3.6 (D) mL/min/kg
Cmax: 12.4 µM (R) PO 10 mg/kg
Area Under the Curve:: 25.4 h.uM (R) PO: 10 mg/kg
Bioavailability: 115 (M), 52 (R), 80 (D) %
Volume of Distribution at Steady-State: 0.9 (M), 0.6 (R), 1.1 (D) L/Kg
Organ of interest (O): liver
Target engagement assay: Rat Dose Escalation PK, PO: Dose (mg/kg): 3, 10, 30, 100, 300 AUC, po (h·μM): 9.2, 25.4, 76.5, 398.7, 1040.2 Cmax, po (μM): 4.5, 12.4, 28.1, 80.9, 140.8 T1/2 (h), po 3.9 5.7 6.3 5.6 6.3 F(%) 63 52 52 82 72 AUC/Dose 3058 2540 2548 3987 3467

DOI Reference: 10.1021/acs.jmedchem.9b01621

Orthogonal Probes def

GW4064

Chemical Information

Molecular Formula C27H22ClN3O4
SMILEs Cn1nc(C(=O)N(Cc2ccccc2)Cc2ccc(C(=O)O)cc2)c2c1-c1cc(Cl)ccc1OC2
InChI InChI=1S/C27H22ClN3O4/c1-30-25-21-13-20(28)11-12-23(21)35-16-22(25)24(29-30)26(32)31(14-17-5-3-2-4-6-17)15-18-7-9-19(10-8-18)27(33)34/h2-13H,14-16H2,1H3,(H,33,34)
Molecular weight 487.13 Da
AlogP 5.1737
HBond acceptors 7
HBond donors 1
Atoms 57

References

Cross References

canSARChEMBLBindingDB

Vendors

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Expert Reviews


(on 19 Dec 2021 )
Cellular Use Rating
In Model Organisms
Good validation data available in cells and in vivo for mice, rats, and dogs. Good selectivity over potential off-targets. Partial FXR agonism in vitro and in a cell based assay for induction of FXR target...
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