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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Nampt-IN-5 targets nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD+ salvage pathway. By inhibiting NAMPT, it depletes intracellular NAD+ levels, leading to energy crisis and cell death in cancer cells. The compound also inhibits CYP3A4 activity, which may have implications for drug-drug interactions.
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| ln Vitro |
The cellular IC50s of Nampt-IN-5 (Compound 27) (0-10 nM; 3 days) against A2780 and COR-L23 are 0.7 nM and 3.9 nM, respectively [1]. CYP3A4 inhibition value (0.75 μM), mouse microsomal clearance (110 μl/min·mg), Sol6.8: 0.056 mM, and MDCK Pap AB: 18.6[1] were among the good ADME results displayed by Nampt-IN-5.
In vitro, Nampt-IN-5 potently inhibits NAMPT with cellular IC50 values of 0.7 nM against A2780 ovarian cancer cells and 3.9 nM against COR-L23 lung cancer cells. The compound demonstrates strong antiproliferative activity and also inhibits CYP3A4 activity. Its potent NAMPT inhibition makes it a valuable tool for studying NAD+ metabolism and cancer biology. |
| ln Vivo |
In comparison to vehicle, Nampt-IN-5 (5-30 mg/kg) delivered orally twice daily for 4 days significantly reduces body weight in nude mice [1]. In mice, T1/2 (2.1 h), Cmax (29112 nM), and AUC (61984 nM·h) are demonstrated by Nampt-IN-5 (10 mg/kg; oral) [1].
In vivo, Nampt-IN-5 is an orally active NAMPT inhibitor with anticancer activity. As an orally bioavailable compound, it can be administered to animal models of cancer to study the effects of NAMPT inhibition on tumor growth. The compound's ability to deplete NAD+ levels and induce cancer cell death translates to in vivo efficacy. Detailed in vivo pharmacokinetic and efficacy studies are available from the compound's characterization. |
| Enzyme Assay |
In vitro enzyme assays for Nampt-IN-5 involve measuring its inhibition of NAMPT activity. Recombinant NAMPT is incubated with increasing concentrations of the compound, nicotinamide, and ATP in assay buffer. The formation of nicotinamide mononucleotide (NMN) is measured by HPLC or coupled enzyme assays. IC50 values are calculated from dose-response curves. CYP3A4 inhibition can be assessed using standard P450 inhibition assays with specific substrates.
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| Cell Assay |
For in vitro cell-based assays, cancer cell lines such as A2780 and COR-L23 are cultured and treated with Nampt-IN-5 at various concentrations. Cell viability is assessed by MTT or CellTiter-Glo assays. NAD+ levels are measured using enzymatic cycling assays or LC-MS. The compound's effects on cellular energy metabolism and apoptosis are evaluated. CYP3A4 activity in cells can be assessed using probe substrates.
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| Animal Protocol |
In vivo animal studies with Nampt-IN-5 are conducted in mouse xenograft models of cancer. Tumor-bearing mice are treated with the compound orally at doses determined from pharmacokinetic studies. Tumor growth inhibition is monitored. At study endpoint, tumors are excised for histopathological and molecular analyses. NAD+ levels in tumors and tissues are measured. Pharmacodynamic markers of NAMPT inhibition are assessed.
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| ADME/Pharmacokinetics |
Nampt-IN-5 (CAS: 2380013-17-0) has a molecular weight of 427.50 g/mol and a molecular formula of C25H25N5O2. Chemical name: N-{4-[(2-ethoxy-1H-1,3-benzodiazol-1-yl)methyl]phenyl}-3-(pyridin-3-yl)azetidine-1-carboxamide. Purity: ≥98%. Solubility: DMSO. Storage: powder at -20°C. The compound is a potent and orally active NAMPT inhibitor.
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| Toxicity/Toxicokinetics |
Nampt-IN-5 is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As a NAMPT inhibitor, it may have effects on normal tissues that rely on NAD+ metabolism. The compound's inhibition of CYP3A4 may affect the metabolism of co-administered drugs. Standard laboratory safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
Nampt-IN-5 is a potent and orally active inhibitor of nicotinamide phosphoribosyltransferase (NAMPT) with cellular IC50 values of 0.7 nM and 3.9 nM against A2780 and COR-L23 cancer cells, respectively. It also inhibits CYP3A4 activity. The compound has a molecular weight of 427.50 g/mol and a molecular formula of C25H25N5O2. It is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C25H25N5O2
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|---|---|
| Molecular Weight |
427.4983
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| Exact Mass |
427.2
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| CAS # |
2380013-17-0
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| PubChem CID |
146014464
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| Appearance |
White to off-white solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
620
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N([H])C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])N1C(=NC2=C([H])C([H])=C([H])C([H])=C12)OC([H])([H])C([H])([H])[H])N1C([H])([H])C([H])(C2=C([H])N=C([H])C([H])=C2[H])C1([H])[H]
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| InChi Key |
JWEBCHOGBDMGBY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H25N5O2/c1-2-32-25-28-22-7-3-4-8-23(22)30(25)15-18-9-11-21(12-10-18)27-24(31)29-16-20(17-29)19-6-5-13-26-14-19/h3-14,20H,2,15-17H2,1H3,(H,27,31)
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| Chemical Name |
N-[4-[(2-ethoxybenzimidazol-1-yl)methyl]phenyl]-3-pyridin-3-ylazetidine-1-carboxamide
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| Synonyms |
NamptIN5 Nampt IN 5
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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 : ~50 mg/mL (~116.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3392 mL | 11.6959 mL | 23.3918 mL | |
| 5 mM | 0.4678 mL | 2.3392 mL | 4.6784 mL | |
| 10 mM | 0.2339 mL | 1.1696 mL | 2.3392 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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