| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
NAMPT inhibitor-linker 1 targets nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the NAD+ salvage pathway that plays a critical role in cellular metabolism and survival. By inhibiting NAMPT, the compound disrupts NAD+ biosynthesis, affecting cellular energy metabolism. As part of an ADC, the NAMPT inhibitor payload is delivered specifically to target cells expressing c-Kit, enabling selective cytotoxicity.
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|---|---|
| ln Vitro |
ADC-3 demonstrates strong efficacy against cell lines that express c-Kit, including GIST-T1 and NCI-H526; its IC50 values are less than 3 pM and 9 pM, respectively [1].
In vitro, NAMPT inhibitor-linker 1, when conjugated as ADC-3 with an anti-c-Kit monoclonal antibody, exhibits potent activity against c-Kit expressing cell lines. It shows IC₅0 values of <3 pM against GIST-T1 cells and 9 pM against NCI-H526 cells. The compound is a potent ADC payload that effectively inhibits the growth of c-Kit positive cancer cells in vitro. |
| ln Vivo |
In mice containing GIST-T1 cells, ADC-3 (20 mg/kg intravenously over 28 days) is tolerogenic and results in tumor stasis [1].
In vivo, ADC-3, which consists of NAMPT inhibitor-linker 1 conjugated to an anti-c-Kit monoclonal antibody, demonstrates potent antitumor activity. The targeted delivery of the NAMPT inhibitor payload via the ADC enables selective tumor cell killing. Further in vivo studies are needed to fully characterize its efficacy and pharmacokinetic profile in various cancer models. |
| Enzyme Assay |
For in vitro binding assays, NAMPT inhibitor-linker 1 can be evaluated using target engagement studies to confirm its interaction with NAMPT. Surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) can be used to measure binding affinity to NAMPT. Enzyme activity assays measuring NAMPT-mediated NAD+ production can determine the inhibitory potency of the payload. Standard assay conditions include physiological buffer systems with appropriate cofactors and substrates.
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| Cell Assay |
For in vitro cellular experiments, NAMPT inhibitor-linker 1 is typically tested as an ADC conjugate in c-Kit expressing cell lines such as GIST-T1 and NCI-H526. Cells are cultured in appropriate media and treated with various concentrations of the ADC. Cell viability and proliferation are assessed using standard assays such as CellTiter-Glo or MTT. The ADC's target-specific cytotoxicity is evaluated by comparing activity in c-Kit positive versus negative cell lines.
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| Animal Protocol |
Animal/Disease Models: Female scid-beige (SCID bg) mice [1]
Doses: 20 mg/kg Route of Administration: Single intravenous (iv) (iv)injection for 28 days. Experimental Results: Dramatically inhibited tumor growth in mice. For in vivo animal experiments, the ADC containing NAMPT inhibitor-linker 1 can be administered to tumor-bearing mice via intravenous injection. Xenograft models using c-Kit expressing cell lines are commonly used. ADC-4 (20 mg/kg, i.v. for 28 days) is tolerated and causes tumor stasis in mice bearing GIST-T1 cells. Tumor volume is measured regularly, and body weight is monitored as an indicator of tolerability. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of NAMPT inhibitor-linker 1 are influenced by its conjugation to an antibody. As part of an ADC, the conjugate is expected to have a longer half-life in circulation and improved tumor accumulation compared to the free payload. Detailed parameters such as Cₘₐₓ, Tₘₐₓ, AUC, half-life, and clearance would need to be determined through comprehensive PK studies of the ADC construct.
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| Toxicity/Toxicokinetics |
Toxicological data for NAMPT inhibitor-linker 1 are limited, as it is a research tool for ADC development. As an NAMPT inhibitor, its toxicity would depend on the importance of NAD+ metabolism for normal cellular function. When delivered as an ADC, off-target toxicity is minimized by targeted delivery to c-Kit expressing cells. Comprehensive toxicology studies would be needed for further development. Appropriate safety precautions should be taken when handling this compound.
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| References | |
| Additional Infomation |
NAMPT inhibitor-linker 1 is a research compound used for ADC development. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound is designed for conjugation to antibodies targeting c-Kit, enabling targeted delivery of the NAMPT inhibitor payload to cancer cells.
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| Molecular Formula |
C36H37FN6O6
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|---|---|
| Molecular Weight |
668.713991880417
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| Exact Mass |
668.275
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| CAS # |
2241019-57-6
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| PubChem CID |
137628672
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| Appearance |
White to light yellow solid powder
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| LogP |
1.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
49
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| Complexity |
1220
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| Defined Atom Stereocenter Count |
2
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| SMILES |
FC1=C(CNC(C2C=CC(=CC=2)N2CCN(C(CCOCCN3C(C=CC3=O)=O)=O)CC2)=O)C=CC(=C1)NC([C@H]1C[C@@H]1C1C=NC=CC=1)=O
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| InChi Key |
ZIJGVXBDFVHKQP-IHLOFXLRSA-N
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| InChi Code |
InChI=1S/C36H37FN6O6/c37-31-20-27(40-36(48)30-21-29(30)25-2-1-12-38-22-25)6-3-26(31)23-39-35(47)24-4-7-28(8-5-24)41-13-15-42(16-14-41)32(44)11-18-49-19-17-43-33(45)9-10-34(43)46/h1-10,12,20,22,29-30H,11,13-19,21,23H2,(H,39,47)(H,40,48)/t29-,30+/m1/s1
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| Chemical Name |
4-[4-[3-[2-(2,5-dioxopyrrol-1-yl)ethoxy]propanoyl]piperazin-1-yl]-N-[[2-fluoro-4-[[(1S,2S)-2-pyridin-3-ylcyclopropanecarbonyl]amino]phenyl]methyl]benzamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~12.5 mg/mL (~18.69 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (1.87 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 12.5 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: ≥ 1.25 mg/mL (1.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (1.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4954 mL | 7.4771 mL | 14.9542 mL | |
| 5 mM | 0.2991 mL | 1.4954 mL | 2.9908 mL | |
| 10 mM | 0.1495 mL | 0.7477 mL | 1.4954 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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