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NMS-P118 | Inhibitor of PARP1
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

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Targets Biochemical/Biophysical Potency Cellular Potency
PARP1
  • Kd:9 nM
  • IC50:40 nM
Inhibitor
100 nM - 1 uM

Selectivity

In Vitro Selectivity Assessment

Potency: KD - PARP2: 1.39 uM, PARP3 (ARTD3): 0.69 uM, TNKS1 (PARP5a): >10 uM

Potency Assay Off-Target:
SPR binding assay
Selectivity Assessment Description:
In CYP inhibition assays, NMS-P118 had only moderate activity against two of eight CYP proteins ( ...
In Cell Selectivity Assessment

Potency: IC50 - SIRT1: >10 uM

Potency Assay Off-Target:
HeLa cell PAR assay. Also in cells, NMS-P118 potently inhibited proliferation of BRCA1-mutant MDA-MB ...

Potency
Cellular
In Vitro

PARP1

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1021/acs.jmedchem.5b00680

In Vivo Validations

Mouse
Dose: 10 mg/Kg
Route of delivery: Intravenous
Plasma half life: 3.3 ± 0.1 h
Systemic clearance: 19.3 ± 2.3 mL/min/kg
Cmax: 5.6 ± 0.1 uM
Area Under the Curve:: 20.7 ± 2.3 μM·h
Volume of Distribution at Steady-State: 3.9 ± 0.1 L/kg

DOI Reference: 10.1021/acs.jmedchem.5b00680

Dose: 10 mg/Kg
Route of delivery: Oral
Plasma half life: 3.1 ± 0.1
Cmax: 5.2 ± 0.6 uM
Area Under the Curve:: 19.7 ± 5.2 uM*h
Bioavailability: 95%

DOI Reference: 10.1021/acs.jmedchem.5b00680

Rat
Dose: 10 mg/Kg
Route of delivery: Intravenous
Plasma half life: 4.7 ± 1.2 h
Systemic clearance: 10.8 ± 2.4 mL/min/Kg
Cmax: 6.0 ± 0.7 uM
Area Under the Curve:: 40.0 ± 8.0 uM*h
Volume of Distribution at Steady-State: 3.5 ± 0.6 L/Kg

DOI Reference: 10.1021/acs.jmedchem.5b00680

Dose: 10 mg/Kg
Route of delivery: Oral
Plasma half life: 3.9 ± 0.1 h
Cmax: 2.8 ± 0.3 uM
Area Under the Curve:: 34 ± 2.9 uM*h
Bioavailability: 87%

DOI Reference: 10.1021/acs.jmedchem.5b00680

Orthogonal Probes def

Olaparib
Talazoparib
VELIPARIB

Chemical Information

Molecular Formula C20H24F3N3O2
SMILEs NC(=O)c1cc(F)cc2c1C(=O)N(C1CCN(C3CCC(F)(F)CC3)CC1)C2
InChI InChI=1S/C20H24F3N3O2/c21-13-9-12-11-26(19(28)17(12)16(10-13)18(24)27)15-3-7-25(8-4-15)14-1-5-20(22,23)6-2-14/h9-10,14-15H,1-8,11H2,(H2,24,27)
Molecular weight 395.18 Da
AlogP 2.9227000000000016
HBond acceptors 5
HBond donors 2
Atoms 52

References

Publications

Cross References

ChEMBL BindingDB PDB PubChem canSAR

Vendors

Note: This is not an exhaustive list and does not indicate endorsement by the Portal.

Expert Reviews

by SERP
(on 28 Jul 2017)
Cellular Use Rating
In Model Organisms
While NMS-P118 is 150-fold selective for PARP-1 over PARP-2 in vitro, cellular target selectivity is not yet clear. However, pharmacokinetics, bioavailability and tolerability in animals are good, so...
by SERP
(on 16 Nov 2020)
Cellular Use Rating
In Model Organisms
...
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