| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Targets |
TES-1025 targets human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), an enzyme involved in the tryptophan catabolic pathway. ACMSD controls the flux of tryptophan metabolites towards NAD+ synthesis. TES-1025 inhibits ACMSD with an IC50 of 13 nM. By inhibiting ACMSD, the compound increases NAD+ levels in cellular systems, with potential implications for diseases involving NAD+ homeostasis.
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| ln Vitro |
The human ACMSD inhibitor TES-1025, which has a low nanomolar concentration, raises NAD+ levels in cellular systems [1].
In vitro, TES-1025 inhibits human ACMSD with an IC50 of approximately 13 nM. It is a potent and highly selective inhibitor. The compound increases NAD+ levels in cellular systems by redirecting tryptophan metabolism away from the ACMSD branch and towards the NAD+ synthesis pathway. This activity positions TES-1025 as a valuable tool for studying NAD+ metabolism and related diseases. |
| ln Vivo |
Male CD-1 mice were used for in vivo pharmacokinetic investigations of TES-1025 after both intravenous (IV) and oral (PO) treatment. TES-1025 demonstrated poor blood clearance, low volume of distribution, and a half-life (t1/2) of roughly 5.33 hours following an intravenous administration of 0.5 mg/kg. On the other hand, the quantitative time of TES-1025 plasma concentration was up to 8 hours following oral dose of 5 mg/kg. For TES-1025, good systemic exposure was reported, and two hours after dosage, a Cmax of 2570 ng/mL was attained. The liver and kidney have higher oral exposure to TES-1025, with AUC0-8h values of 19 200 h·ng/mL and 36 600 h·ng/mL, respectively [1].
In vivo, TES-1025 is expected to increase NAD+ levels in tissues by inhibiting ACMSD. Defects in NAD+ homeostasis are associated with a wide range of diseases, including cancer, metabolic disorders, and aging. By increasing NAD+ levels, TES-1025 may have therapeutic potential for these conditions. Detailed in vivo efficacy and pharmacokinetic data are available in research publications. |
| Enzyme Assay |
In vitro enzyme assays for TES-1025 measure its inhibition of human ACMSD activity. The enzyme is incubated with its substrate, α-amino-β-carboxymuconate-ε-semialdehyde (ACMS), in the presence of varying concentrations of the compound. The decarboxylation product is quantified by HPLC or spectrophotometric methods. The IC50 of 13 nM is determined from dose-response curves. Selectivity is assessed by testing against other enzymes in the tryptophan catabolic pathway.
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| Cell Assay |
In vitro cell-based assays for TES-1025 use cultured human cells, such as hepatocytes or other cell lines. Cells are treated with serial dilutions of the compound, and NAD+ levels are quantified using enzymatic cycling assays or LC-MS/MS. The compound's ability to increase NAD+ levels is measured over time. Cellular viability and toxicity are assessed in parallel. The effects on downstream metabolic pathways and gene expression may also be evaluated.
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| Animal Protocol |
In vivo animal models for TES-1025 include mouse models of NAD+ deficiency or diseases associated with NAD+ depletion, such as metabolic disorders or neurodegenerative diseases. The compound is administered orally or intraperitoneally, and NAD+ levels are measured in tissues such as liver, brain, and muscle. Pharmacodynamic markers include ACMSD inhibition and NAD+ elevation. Efficacy is evaluated in disease models by assessing relevant clinical or biochemical endpoints.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of TES-1025 have been characterized in preclinical studies. The compound has a molecular weight of 383.44 g/mol and is soluble in DMSO at 90 mg/mL. Its oral bioavailability, half-life, and tissue distribution are documented in research publications. The compound is stored as powder at -20°C for 3 years or in solution at -80°C for 6 months. Detailed PK parameters are available in the scientific literature.
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| Toxicity/Toxicokinetics |
Toxicity data for TES-1025 are available from preclinical safety studies. As a small-molecule inhibitor, the compound's toxicity profile is assessed in standard toxicology studies in rodents. The no-observed-adverse-effect level (NOAEL) and maximum tolerated dose (MTD) are determined from dose-escalation studies. Target-related toxicities, including effects on NAD+ metabolism and tryptophan homeostasis, are evaluated.
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| References |
[1]. Pellicciari R, et al. α-Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide (NAD+) Biosynthesis. J Med Chem. 2018 Feb 8;61(3):745-759
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| Additional Infomation |
TES-1025 is a research compound that has not been approved for clinical use. It is the first potent and selective inhibitor of human ACMSD. By increasing NAD+ levels in cells, the compound has potential applications in the study and treatment of cancer, metabolic disorders, and aging. Its high potency (IC50 = 13 nM) and selectivity make it a valuable tool for NAD+ metabolism research.
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| Molecular Formula |
C18H13N3O3S2
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|---|---|
| Molecular Weight |
383.44412112236
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| Exact Mass |
383.039
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| Elemental Analysis |
C, 56.38; H, 3.42; N, 10.96; O, 12.52; S, 16.72
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| CAS # |
1883602-21-8
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| PubChem CID |
137142885
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| Appearance |
Solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
695
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
RJQYGCGMQYVVIB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H13N3O3S2/c19-9-13-16(14-5-2-6-25-14)20-18(21-17(13)24)26-10-12-4-1-3-11(7-12)8-15(22)23/h1-7H,8,10H2,(H,22,23)(H,20,21,24)
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| Chemical Name |
2-[3-[(5-cyano-6-oxo-4-thiophen-2-yl-1H-pyrimidin-2-yl)sulfanylmethyl]phenyl]acetic acid
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| Synonyms |
TES1025; TES 1025; TES-1025
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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 : ~100 mg/mL (~260.80 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.52 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 (6.52 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 | 2.6080 mL | 13.0398 mL | 26.0797 mL | |
| 5 mM | 0.5216 mL | 2.6080 mL | 5.2159 mL | |
| 10 mM | 0.2608 mL | 1.3040 mL | 2.6080 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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