| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg | |||
| 25mg | |||
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| Other Sizes |
| Targets |
TES-991 targets human alpha-amino-beta-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), a key enzyme in the tryptophan catabolism pathway that regulates NAD+ biosynthesis. ACMSD catalyzes the decarboxylation of alpha-amino-beta-carboxymuconate-ε-semialdehyde, diverting tryptophan metabolites away from the de novo NAD+ synthesis pathway. TES-991 inhibits ACMSD with an IC50 of 3 nM, thereby blocking this diversion and increasing flux through the NAD+ biosynthesis pathway, leading to elevated intracellular NAD+ levels.
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| ln Vitro |
The ability of TES-991 (compound 21) to dramatically raise intracellular NAD+ levels provides more evidence for its mode of action. Cytochrome P450 2C19 is inhibited by TES-991, indicating that the 2H-tetrazole motif may be implicated in this interaction [1].
In vitro, TES-991 potently inhibits human ACMSD with an IC50 of 3 nM. The compound's potent inhibition of ACMSD leads to increased intracellular NAD+ levels by modulating tryptophan metabolism. TES-991 is a novel, potent, and selective ACMSD inhibitor. Its in vitro activity has been characterized in enzymatic assays using purified recombinant ACMSD. The compound is used as a research tool to study NAD+ metabolism and its role in cellular physiology. |
| ln Vivo |
TES-991 (compound 21) demonstrated low blood clearance, low volume of distribution, and half-lives (t1/2) of roughly 4.0 and 5.0 hours following an intravenous injection of 0.5 mg/kg; however, following oral administration of 5 mg/kg, TES- Blood concentrations of 991 can be measured for up to 8 hours. Good systemic exposure was documented with the free acid, while moderate systemic exposure was noted with the 2H-tetrazole analogue TES-991 [1].
Detailed in vivo activity data for TES-991 are not extensively documented in publicly available literature. As an ACMSD inhibitor that increases NAD+ levels, TES-991 is being investigated for its potential therapeutic applications in aging, metabolic diseases, and neurodegenerative disorders. By increasing NAD+ levels, the compound may activate sirtuins and other NAD+-dependent enzymes that play roles in cellular metabolism, stress resistance, and longevity. Further in vivo studies are needed to fully characterize its therapeutic potential. |
| Enzyme Assay |
Enzyme activity assays for TES-991 are performed using purified recombinant human ACMSD. ACMSD activity is measured by monitoring the decarboxylation of alpha-amino-beta-carboxymuconate-ε-semialdehyde (ACMS) to picolinic acid. TES-991 is incubated with the enzyme and substrate at varying concentrations in appropriate assay buffer. The reaction is stopped, and product formation is quantified by HPLC or LC-MS. IC50 values are calculated from concentration-response curves. Nonspecific activity is determined in control reactions without inhibitor.
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| Cell Assay |
Cellular assays for TES-991 are performed using cell lines that express ACMSD, such as hepatocytes or neuronal cells. Cells are cultured in appropriate media and treated with TES-991 at varying concentrations for defined time periods. Intracellular NAD+ levels are measured using enzymatic cycling assays or LC-MS. The effects on NAD+-dependent processes such as sirtuin activity are assessed by measuring the acetylation status of sirtuin substrates by Western blot. Cell viability and proliferation may also be assessed.
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| Animal Protocol |
In vivo studies with TES-991 are conducted in animal models to evaluate the compound's ability to increase NAD+ levels and modulate metabolism. TES-991 is administered via appropriate routes (e.g., oral or intraperitoneal) at defined doses and schedules. NAD+ levels in tissues such as liver, brain, and muscle are measured by LC-MS. Metabolic parameters such as glucose tolerance and insulin sensitivity may be assessed. The compound's effects on aging and age-related diseases are being investigated.
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| ADME/Pharmacokinetics |
TES-991 has a molecular weight of 393.45 and a molecular formula of C17H11N7OS2. The compound is a potent and selective ACMSD inhibitor with an IC50 of 3 nM. Detailed pharmacokinetic parameters, including oral bioavailability and half-life, have been characterized in preclinical studies. The compound is supplied as a light yellow to yellow solid powder with a purity of ≥98%.
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| Toxicity/Toxicokinetics |
TES-991 is a research compound and comprehensive toxicology data are not extensively documented in publicly available sources. The compound is intended for research use only and is not approved for human therapeutic applications. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and adherence to institutional biosafety and chemical hygiene guidelines. The compound has a purity of ≥98%.
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| References | |
| Additional Infomation |
TES-991 is a potent and selective small-molecule inhibitor of human alpha-amino-beta-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) with an IC50 of 3 nM. By blocking ACMSD catalytic activity, TES-991 modulates tryptophan metabolism and NAD+ biosynthesis, increasing intracellular NAD+ levels. TES-991 is used as a research tool to study NAD+ metabolism and its role in aging and metabolic diseases. The compound is for research purposes only.
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| Molecular Formula |
C17H11N7OS2
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|---|---|
| Molecular Weight |
393.445538759232
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| Exact Mass |
393.046
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| CAS # |
1883602-20-7
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| PubChem CID |
137142884
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
701
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)C2=NNN=N2)CSC3=NC(=C(C(=O)N3)C#N)C4=CC=CS4
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| InChi Key |
VCDQAPTULMMFKX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H11N7OS2/c18-8-12-14(13-5-2-6-26-13)19-17(20-16(12)25)27-9-10-3-1-4-11(7-10)15-21-23-24-22-15/h1-7H,9H2,(H,19,20,25)(H,21,22,23,24)
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| Chemical Name |
6-oxo-2-[[3-(2H-tetrazol-5-yl)phenyl]methylsulfanyl]-4-thiophen-2-yl-1H-pyrimidine-5-carbonitrile
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| Synonyms |
TES 991 TES991 TES-991
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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 : ~62.5 mg/mL (~158.85 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.29 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 20.8 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: ≥ 2.08 mg/mL (5.29 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 20.8 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 | 2.5416 mL | 12.7081 mL | 25.4162 mL | |
| 5 mM | 0.5083 mL | 2.5416 mL | 5.0832 mL | |
| 10 mM | 0.2542 mL | 1.2708 mL | 2.5416 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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