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| Targets |
NMS-P515 primarily targets poly(ADP-ribose) polymerase 1 (PARP-1), an enzyme involved in DNA repair. PARP-1 detects and repairs single-strand DNA breaks; its inhibition leads to the accumulation of DNA damage and cell death, particularly in cancer cells with defective homologous recombination repair. The compound binds to the PARP enzyme's active site with high affinity (Kd = 16 nM).
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| ln Vitro |
NMS-P515 demonstrates potent in vitro activity as a PARP-1 inhibitor with a biochemical Kd of 16 nM and a cellular IC₅₀ of 27 nM in HeLa cells. It exhibits strong antiproliferative effects across various tumor models, including solid and hematologic malignancies. Its in vitro activity is assessed using both biochemical and cellular assays to confirm PARP-1 inhibition.
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| ln Vivo |
In a mouse model of pancreatic cancer, NMS-P515 (80 mg/kg orally daily for 12 days) showed strong anticancer efficacy [1].
In vivo activity of NMS-P515 has been demonstrated in animal models of cancer, where it shows anti-tumor efficacy. As an orally active compound, it is suitable for oral administration in preclinical studies. Its in vivo efficacy is evaluated in xenograft models by measuring tumor growth inhibition and survival outcomes. The compound's oral bioavailability supports its development as a therapeutic agent. |
| Enzyme Assay |
The in vitro enzyme assay for NMS-P515 involves measuring its inhibitory activity against PARP-1 in cell-free systems. These assays use purified PARP-1 enzyme and measure the incorporation of NAD⁺ into poly(ADP-ribose) polymers in the presence of the compound. Inhibitory potency is determined by assessing the reduction in enzyme activity, with a Kd of 16 nM reported for PARP-1 binding.
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| Cell Assay |
In vitro cellular assays for NMS-P515 are performed using cancer cell lines such as HeLa cells. These assays measure the compound's ability to inhibit PARP-1 activity in intact cells, with an IC₅₀ of 27 nM reported. Cellular assays may also assess the compound's antiproliferative effects and its ability to induce DNA damage and cell death in various tumor cell lines.
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| Animal Protocol |
Animal/Disease Models: Capan-1 pancreatic (BRCA2 mutated) mouse xenograft implanted subcutaneously (sc) (sc) [1].
Doses: 80 mg/kg. Route of Administration: po (po (oral gavage)) one time/day for 12 days. Experimental Results: Significant reduction in tumor growth (maximum observed tumor growth inhibition: 48%, maximum weight loss: 6%). In vivo animal studies for NMS-P515 are conducted in mouse xenograft models of various cancers. These studies typically involve oral administration of the compound, followed by assessment of tumor growth inhibition, survival, and pharmacodynamic markers of PARP inhibition. The compound's oral activity and anti-tumor efficacy are evaluated in these models to support its therapeutic potential. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of NMS-P515 are characterized by oral activity and bioavailability. As an orally active compound, it is designed for systemic administration and has favorable ADME properties. The compound's molecular formula is C₂₁H₂₉N₃O₂ with a molecular weight of 355.47 g/mol. Its pharmacokinetic profile supports once- or twice-daily dosing in preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicology studies of NMS-P515 have been conducted to support its development as an anticancer agent. These studies include acute and repeat-dose toxicity assessments in preclinical species, as well as genotoxicity and safety pharmacology evaluations. As a PARP-1 inhibitor, its toxicology profile includes effects on bone marrow and gastrointestinal tissues, which are common to this class of compounds.
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| References | |
| Additional Infomation |
NMS-P515 (CAS: 1262395-13-0) is a potent, orally active PARP-1 inhibitor with a Kd of 16 nM and an IC₅₀ of 27 nM in HeLa cells. It exhibits anti-tumor activity and is used in cancer research. The compound has a molecular formula of C₂₁H₂₉N₃O₂ and a molecular weight of 355.47 g/mol. It is for research use only and is not for human therapeutic use.
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| Molecular Formula |
C21H29N3O2
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| Molecular Weight |
355.473865270615
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| Exact Mass |
355.225
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| CAS # |
1262395-13-0
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| Related CAS # |
1262395-13-0;1262395-10-7 (recemate);1262395-17-4 (R-isomer);
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| PubChem CID |
49843530
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| Appearance |
White to off-white solid powder
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| LogP |
2.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
537
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1C2C(C(N)=O)=CC=CC=2[C@H](C)N1C1CCN(CC1)C1CCCCC1
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| InChi Key |
OYGLTKXMFGWXJT-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C21H29N3O2/c1-14-17-8-5-9-18(20(22)25)19(17)21(26)24(14)16-10-12-23(13-11-16)15-6-3-2-4-7-15/h5,8-9,14-16H,2-4,6-7,10-13H2,1H3,(H2,22,25)/t14-/m0/s1
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| Chemical Name |
(1S)-2-(1-cyclohexylpiperidin-4-yl)-1-methyl-3-oxo-1H-isoindole-4-carboxamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~3.33 mg/mL (~9.37 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8132 mL | 14.0659 mL | 28.1318 mL | |
| 5 mM | 0.5626 mL | 2.8132 mL | 5.6264 mL | |
| 10 mM | 0.2813 mL | 1.4066 mL | 2.8132 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.
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.
(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.
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