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| 10mg |
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| Targets |
MK-0159 targets CD38, a multifunctional ectoenzyme that catalyzes the synthesis and hydrolysis of cyclic ADP-ribose (cADPR) from NAD⁺. By inhibiting CD38, MK-0159 prevents the degradation of NAD⁺, thereby increasing NAD⁺ levels. This is thought to be protective in conditions of cardiac ischemia and reperfusion injury, where NAD⁺ depletion contributes to cell damage. The compound is highly potent, particularly against mouse CD38.
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| ln Vitro |
In vitro, MK-0159 is a potent inhibitor of CD38 enzymatic activity. It has IC₅₀ values of 22 nM for human CD38, 3 nM for mouse CD38, and 70 nM for rat CD38 in cell-free assays. In CD38-expressing human epithelial A549 cells, MK-0159 increases extracellular and intracellular NAD⁺ levels. These data confirm its mechanism of action as a CD38 inhibitor.
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| ln Vivo |
In vivo, MK-0159 has been shown to increase systemic NAD⁺ and decrease ADPR levels in mice at doses of 3-30 mg/kg administered orally. It provides strong protection from myocardial damage upon cardiac ischemia/reperfusion injury compared to NAD⁺ precursors or the known CD38 inhibitor 78c. These findings support its potential for treating cardiac ischemia and reperfusion injury.
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| Enzyme Assay |
A cell-free assay for MK-0159 involves measuring its inhibition of CD38 enzymatic activity. In such assays, recombinant CD38 enzyme is incubated with a substrate (e.g., NAD⁺ or a fluorogenic substrate) and varying concentrations of the compound. The rate of substrate conversion is measured, and IC₅₀ values are calculated. For MK-0159, IC₅₀ values of 22 nM (human), 3 nM (mouse), and 70 nM (rat) have been reported.
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| Cell Assay |
Cellular assays for MK-0159 typically involve measuring NAD⁺ levels in CD38-expressing cells. Cells are treated with varying concentrations of the compound, and NAD⁺ levels are quantified using enzymatic cycling assays or LC-MS. In A549 cells, MK-0159 increases both extracellular and intracellular NAD⁺ levels. This confirms the compound's ability to inhibit CD38 in a cellular context.
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| Animal Protocol |
In vivo animal experiments with MK-0159 have been conducted in mice. Mice were administered MK-0159 orally at doses of 3-30 mg/kg. The compound increased systemic NAD⁺ levels and decreased ADPR levels. In models of cardiac ischemia/reperfusion injury, MK-0159 provided strong protection from myocardial damage. These studies demonstrate the in vivo efficacy of MK-0159 as a cardioprotective agent.
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| ADME/Pharmacokinetics |
MK-0159 is an orally bioavailable compound. In mice, oral administration at doses of 3-30 mg/kg resulted in increased systemic NAD⁺ levels. Specific pharmacokinetic parameters, such as half-life, Cmax, and AUC, are not provided in the available sources. The compound is designed for oral administration in the study of cardiac ischemia and reperfusion injury.
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| Toxicity/Toxicokinetics |
Toxicity data for MK-0159 are not detailed in the available sources. As a research compound being studied for cardioprotection, its safety profile is still being established. The compound is intended for research use only and is not for human consumption. Standard laboratory safety precautions should be observed when handling this compound.
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| References |
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| Additional Infomation |
MK-0159 (CAS: 2641484-61-7) is an orally active, potent, and selective CD38 inhibitor. It is also known as compound 37. The compound inhibits human, mouse, and rat CD38 with IC₅₀ values of 22 nM, 3 nM, and 70 nM, respectively. MK-0159 provides myocardial injury protection and is being studied for cardiac ischemia and reperfusion injury. Its mechanism of action involves increasing NAD⁺ levels by inhibiting CD38-mediated NAD⁺ consumption. It is not an approved drug and is strictly for research purposes.
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| Molecular Formula |
C20H24N4O3S
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|---|---|
| Molecular Weight |
400.494563102722
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| Exact Mass |
400.156
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| CAS # |
2641484-61-7
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| PubChem CID |
156339417
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| Appearance |
White to off-white solid powder
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
28
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| Complexity |
518
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C12NC=CC1=C(C(N[C@@H]1CC[C@@H](OCCOC)CC1)=O)C=C(C1SC=NC=1)N=2
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| InChi Key |
VLCKVERFBNFIRC-WKILWMFISA-N
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| InChi Code |
InChI=1S/C21H26N4O3S/c1-27-8-9-28-16-4-2-15(3-5-16)24-20(26)11-14-10-18(19-12-22-13-29-19)25-21-17(14)6-7-23-21/h6-7,10,12-13,15-16H,2-5,8-9,11H2,1H3,(H,23,25)(H,24,26)/t15-,16-
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| Chemical Name |
N-((1r,4r)-4-(2-methoxyethoxy)cyclohexyl)-2-(6-(thiazol-5-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)acetamide
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| Synonyms |
MK0159 MK-0159 MK 0159
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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 and light. |
| 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 : ~100 mg/mL (~249.69 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.24 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 (6.24 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 25.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4969 mL | 12.4847 mL | 24.9694 mL | |
| 5 mM | 0.4994 mL | 2.4969 mL | 4.9939 mL | |
| 10 mM | 0.2497 mL | 1.2485 mL | 2.4969 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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