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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

Targets Biochemical/Biophysical Potency Cellular Potency
PARP1
  • KD:0.009 uM
  • IC50:0.04 uM
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? No

In Vivo Validations

Harlan nu/nu mouse, Sprague Dawley rat
Dose: 10 mg/kg
Route of delivery: Intravenous, Oral
Plasma half life: 3.3 h (mouse, IV), 3.1 h (mouse, oral), 4.7 h (rat, IV), 3.9 h (rat, oral)
Systemic clearance: 19.3 mL/min/kg (mouse, IV); 10.8 (rat, IV)
Organ of interest (O): xenograft
Target engagement assay: In Caplan-1 xenograft, NMS-P118 inhibited PAR production in the tumor.

Reference: --

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

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    Vendors

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    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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