NMS-P118

Alias: NMS-P118; NMS-P 118; NMS P118

Cat No.:V2692 Purity: ≥98%

COA Product Data Instructions for use SDS

NMS-P118 is a novel potent, orally available, and highly selective PARP-1 (protein poly(ADP-ribose) polymerase-1) inhibitor with150-fold selectivity for PARP-1 over PARP-2 (Kd 0.009 μM vs 1.39 μM, respectively).

NMS-P118 Chemical Structure CAS No.: 1262417-51-5
Product category: PARP

This product is for research use only, not for human use. We do not sell to patients.

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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

NMS-P118 (NMS-P-118) is a novel potent, orally bioavailable, and highly selective PARP-1 (protein poly(ADP-ribose) polymerase-1) inhibitor with anticancer activity. It demonstrates a 150-fold preference for PARP-1 over PARP-2 (Kd 0.009 μM versus 1.39 μM, in that order). Treatment for cancer with it has been studied. Out of eight isoforms tested, NMS-P118 modestly inhibits two members of the cytochrome P450 family (CYP-2B6 IC50, 8.15 μM; CYP-2D6 IC50, 9.51 μM). It also demonstrates excellent ADME and pharmacokinetic properties and is metabolically stable. NMS-P118 has a full oral bioavailability and a low in vivo clearance.

Biological Activity I Assay Protocols (From Reference)

Targets

PARP-1 ( Kd = 9 nM ); PARP-2 ( Kd = 1390 nM )

ln Vitro

In vitro activity: NMS-P118 is discovered to be less myelotoxic in vitro than the dual PARP-1/-2 inhibitor olaparib, which is currently marketed as Lynparza. Out of eight isoforms tested, NMS-P118 demonstrates metabolic stability and modest inhibition of two cytochrome P450 family members (CYP-2B6 IC50: 8.15 μM; CYP-2D6 IC50: 9.51 μM). Depending on the species, it can inhibit bone marrow cell proliferation 5–60 times less effectively than olaparib.

ln Vivo

NMS-P118 is demonstrated to be metabolically stable and, of the eight isoforms examined, it only slightly inhibits two members of the cytochrome P450 family (CYP-2B6 IC50, 8.15 μM; CYP-2D6 IC50, 9.51 μM). NMS-P118 has a full oral bioavailability and a low in vivo clearance. The pharmacokinetic profile of NMS-P118 in rats administered orally at 10 and 100 mg/kg and intravenously at 10 mg/kg is similar to that seen in mice, with oral bioavailability exceeding 65% and dose-dependent exposure linearity. At 1, 2, and 6 hours after administration, its treatment significantly lowers intratumoral PAR levels; at 24 hours, partial recovery of PAR levels is seen. In BRCA1-mutant MDA-MB-436 and BRCA2 deficient Capan-1 human tumor xenograft models, respectively, NMS-P118 exhibits excellent ADME and pharmacokinetic profiles, high oral availability in mice and rats, and high efficacy both as a single agent and in combination with Temozolomide.

Enzyme Assay

NMS-P118 is characterized by 56 distinct kinases profiles (ABL, ACK1, AKT1, ALK, AUR1, AUR2, BRK, BUB1, CDC7/DBF4, CDK2/CYCA, CHK1, CK2, EEF2K, EGFR1, ERK2, EphA2, FAK, FGFR1, FLT3, GSK3beta, Haspin, IGFR1, IKK2, IR, JAK1, JAK2, JAK3, KIT, LCK, LYN, MAPKAPK2, MELK, MET, MNK2, MPS1, MST4, NEK6, NIM1, P38alpha, PAK4, POLYDATINGFRb, POLYDATINK1, PERK, PIM1, PIM2, PKAalpha, PLK1, RET, SULU1, Syk, TLK2, TRKA, TYK2, VEGFR2, ZAP70). For every enzyme tested, the IC50 values are found to be greater than 10 μM[1].

Cell Assay

NMS-P118 is diluted with the proper medium and dissolved in DMSO prior to usage. By evaluating the inhibition of hydrogen peroxide-induced PAR formation in HeLa cells (ECACC), PARP-1 inhibitors' cellular activity is determined. ArrayScan vTi is used to quantify the levels of cellular PAR after they are determined by immunocytochemistry[1].

Animal Protocol

Ad Hoc pharmacokinetic studies have been conducted on rats to examine the oral bioavailability and pharmacokinetic profile of the compounds. NMS-P118 is designed to be administered as an intravenous bolus in a 20% DMSO + 40% PEG 400 solution in 5% milk sugar. With 0.5% methylcellulose, an NMS-P118 suspension is used for oral drug administration. For every delivery method, there is one oral administration at a dose of 100 mg/kg and one single administration at a dose of 10 mg/kg. Each study employs three male animals[1].

References

[1]. Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy. J Med Chem. 2015 Sep 10;58(17):6875-98.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C20H24F3N3O2

Molecular Weight

395.42

Exact Mass

395.18

Elemental Analysis

C, 60.75; H, 6.12; F, 14.41; N, 10.63; O, 8.09

CAS #

1262417-51-5

Related CAS #

1262417-51-5

Appearance

Solid powder

SMILES

C1CC(CCC1N2CCC(CC2)N3CC4=C(C3=O)C(=CC(=C4)F)C(=O)N)(F)F

InChi Key

ARYVAQSYRLZVQD-UHFFFAOYSA-N

InChi Code

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)

Chemical Name

2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-1H-isoindole-4-carboxamide

Synonyms

NMS-P118; NMS-P 118; NMS P118

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: 16~24 mg/mL (40.5~60.7 mM)

Water: <1 mg/mL

Ethanol: ~5 mg/mL (~12.6 mM)

Solubility (In Vivo)

O=C(C1=CC(F)=CC(CN2C3CCN(C4CCC(F)(F)CC4)CC3)=C1C2=O)N

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5290 mL	12.6448 mL	25.2896 mL
	5 mM	0.5058 mL	2.5290 mL	5.0579 mL
	10 mM	0.2529 mL	1.2645 mL	2.5290 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

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Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Biological Data

J Med Chem.2015 Sep 10;58(17):6875-98.