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Formula | C20H24F3N3O2 |
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Molecular Weight | 395.42 | CAS No. | 1262417-51-5 | |
Solubility (25°C)* | In vitro | DMSO | 79 mg/mL (199.78 mM) | |
Ethanol | 10 mg/mL (25.28 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
Description | NMS-P118 is a potent, orally available, and highly selective PARP-1 inhibitor 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). | ||
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In vitro | NMS-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[1]. | ||
In vivo | NMS-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[1]. |
Cell Assay:[1] |
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Animal Study:[1] |
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Haploinsufficiency of ZNF251 causes DNA-PKcs-dependent resistance to PARP inhibitors in BRCA1-mutated cancer cells [ Res Sq, 2023, rs.3.rs-2688694] | PubMed: 37066268 |
Haploinsufficiency of ZNF251 causes DNA-PKcs-dependent resistance to PARP inhibitors in BRCA1-mutated cancer cells [ Res Sq, 2023, rs.3.rs-2688694] | PubMed: 37066268 |
Poly (ADP-ribose) polymerase 1 (PARP1) inhibition promotes pulmonary metastasis of osteosarcoma by boosting ezrin phosphorylation [ Int J Biol Sci, 2022, 18(3):1238-1253] | PubMed: 35173550 |
CRISPR screening identifies novel PARP inhibitor classification based on distinct base excision repair pathway dependencies [ bioRxiv, 2021, 10.1101/2020.10.18.333070] | PubMed: None |
Response of Breast Cancer Cells to PARP Inhibitors Is Independent of BRCA Status. [ J Clin Med, 2020, 30;9(4)] | PubMed: 32235451 |
Enabling drug discovery for the PARP protein family through the detection of mono-ADP-ribosylation [ Biochem Pharmacol, 2019, 10.1016/j.bcp.2019.05.007] | PubMed: 31075269 |
DNA‑PKcs PARylation regulates DNA‑PK kinase activity in the DNA damage response. [ Mol Med Rep, 2019, 20(4):3609-3616] | PubMed: 31485633 |
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
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