TES-1025 |
| رقم الكتالوجGC31326 |
TES-1025 هو مثبط فعال وانتقائي لـ α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) مع IC50 من 13 نانومتر
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Cas No.: 1883602-21-8
Sample solution is provided at 25 µL, 10mM.
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TES-1025 is a potent and selective human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) inhibitor with an IC50 of 13±3 nM.
TES-1025 is a low nanomolar human ACMSD inhibitor, which increases NAD+ levels in cellular systems[1].
TES-1025 is subjected to in vivo pharmacokinetic studies, following intravenous (IV) and oral (PO) dosings of male CD-1 mice. After the intravenous administration of 0.5 mg/kg, TES-1025 shows low blood clearance, with low volumes of distribution and half-lives (t1/2) of about 5.33 h, although after oral administration at 5 mg/kg, the blood concentration of TES-1025 is quantifiable for up to 8 h. A good systemic exposure is recorded for TES-1025, with a Cmax of 2570 ng/mL reaches at 2 h after dosing. The greater oral exposure of TES-1025 is further confirmed in the liver and kidneys with AUC0-8h of 19?200 h•ng/mL and 36?600 h•ng/mL, respectively[1].
[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.
Kinase experiment: | Recombinant hACMSD is expressed in Pichia pastoris and purified. Its enzyme activity is assayed by a coupled spectrophotometric assay. Briefly, in a pre-assay mixture, the ACMS substrate is generated from 10 μM 3-hydroxyanthranilic acid by recombinant 3-hydroxyanthranilate 3,4-dioxigenase from Ralstonia metallidurans. ACMS formation is monitored at 360 nm, and after the reaction is complete, an appropriate amount of ACMSD is added. Activity is calculated from the initial rate of the absorbance decrease subtracted from that of a control reaction mixture in the absence of ACMSD. The effects of the various compounds (e.g., TES-1025) on the enzyme activity are tested by adding the compounds to the assay mixture along with ACMSD. For the IC50 evaluations for each compound, a serial dilution from a stock solution prepared in DMSO is tested, maintaining a DMSO concentration in all the reaction mixtures of 1.0%. One unit is defined as the amount of enzyme that consume 1 μmol of ACMS per minute at 37°C[1]. |
Animal experiment: | Mice[1]Male CD-1 mice are used.The study is conducted in 3 phases. Phase 1: 18 mice receive an oral administration of TES-1025 at a target dose level of 5 mg/kg. Blood, brain and liver are collected at intervals up to 8 h after dose administration (n=3 animals per each time point). Phase 2: 3 mice receive each an intravenous administration of TES-1025 at a target dose of 0.5 mg/kg. Blood samples are collected from the lateral tail vein at intervals up to 24 h after dose administration. Phase 3: 3 mice receive a single intravenous administration of Elacridar (5 mg/kg) shortly before an oral administration of TES-1025 at a target dose of 5 mg/kg. Blood and brain samples are collected 0.5 h after dose administration. Brain, liver and kidney are collected from all animals of the study[1]. |
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. | |
| Cas No. | 1883602-21-8 | SDF | |
| Canonical SMILES | O=C1C(C#N)=C(C2=CC=CS2)N=C(SCC3=CC=CC(CC(O)=O)=C3)N1 | ||
| Formula | C18H13N3O3S2 | M.Wt | 383.44 |
| الذوبان | DMSO : 100 mg/mL (260.80 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.608 mL | 13.0398 mL | 26.0797 mL |
| 5 mM | 0.5216 mL | 2.608 mL | 5.2159 mL |
| 10 mM | 0.2608 mL | 1.304 mL | 2.608 mL |
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Quality Control & SDS
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- Purity: >98.00%
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