NMS-P118 (C007B-392414)

InformationNMS-P118 is a potent, orally available, and highly selectivePARP-1inhibitor endowed with excellent ADME and pharmacokinetic profiles, showing 150-fold selectivity for PARP-1 over PARP-2 (Kd 0.009 μM vs 1.39 μM, respectively).TargetsPARP1 (Cell-free assay) 0.009 μM(Kd)In vitroNMS-P118 is a potent (KD = 0.009 μM) PARP-1 inhibitor, showing 150-fold selectivity over PARP-2 (KD = 1.39 μM). The compound shows high solubility and permeability.In vivoNMS-P118 is proved to be metabolically stable, it modestly inhibits two cytochrome P450 family members (CYP-2B6 IC50, 8.15 μM; CYP-2D6 IC50, 9.51 μM) out of eight isoforms tested. NMS-P118 has low in vivo clearance, and complete oral bioavailability. The pharmacokinetic profile of NMS-P118 in rat dosed iv at 10 mg/kg and orally at 10 and 100 mg/kg, mirrors that observed in the mouse, with oral bioavailability >65%, and linearity of exposure with dose. Its treatment dramatically decreases intratumoral PAR levels at 1, 2, and 6 h after administration and partial recovery of PAR levels is observed at 24 h. NMS-P118 shows excellent ADME and pharmacokinetic profiles, high oral availability in the mouse and rat, and high efficacy both as a single agent and in combination with Temozolomide in BRCA1-mutated MDA-MB-436 and BRCA2 deficient Capan-1 human tumor xenograft models, respectively.Cell Research(from reference)Cell lines：HeLa cells Incubation Time：30 mins. Specification: 10mM in DMSO Molecular Formula: C20H24F3N3O2 Molecular Weight: 395.42 PubChem CID: 49843531 Isomeric SMILES: C1CC(CCC1N2CCC(CC2)N3CC4=C(C3=O)C(=CC(=C4)F)C(=O)N)(F)F

UPC:

12352200

Condition:

New

Weight:

0.85 Ounces

HazmatClass:

No

Quantity:

1

Unit of Measurement:

EA

WeightUOM:

LB

MPN:

N421100-1ml

CAS:

1262417-51-5

Product Size:

1ml