NMS-P118

Inhibitor of PARP1

Structure

Information

  • PARP1
  • Inhibitor

In Vitro Validations

Uniprot ID: P09874
Target Class: Other post-translational modification
Target SubClass: PARP
Potency: KD
Potency Value: 0.009 uM
Potency Assay: SPR binding assay
PDB ID for probe-target interaction (3D structure): 5A00
Structure-activity relationship: Yes, see J Med Chem paper
Target aliases:
Poly [ADP-ribose] polymerase 1, PPOL, ADPRT, PARP1 ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : KD PARP2: 1.39 uM, PARP3 (ARTD3): 0.69 uM, TNKS1 (PARP5a): >10 uM
Potency assay (off target): SPR binding assay
Probe Selectivity in Vitro:

In CYP inhibition assays, NMS-P118 had only moderate activity against two of eight CYP proteins (IC50: CYP2B6 8.15 uM; CYP2D6 9.51 uM). In a panel of 56 kinases, NMS-P118 yielded IC50s > 10 uM.

Potency in cells, off target : IC50 SIRT1: >10 uM
Potency assay, off target (cells): HeLa cell PAR assay. Also in cells, NMS-P118 potently inhibited proliferation of BRCA1-mutant MDA-MB-436 triple negative breast cancer cells (IC50=0.4 uM) but not non-BRCA1-mutant cell lines (IC50 >10 uM).
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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

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 this could be a good in vivo probe.

(last updated: 28 Jul 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

NMS-P118 is a cellularly active and bioavailable selective PARP-1 inhibitor. This chemical probe is an excellent choice for investigating PARP-1 biology either in a cellular or an in vivo context.

(last updated: 16 Nov 2020 )