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Purity: ≥98%
TGN-020 (TGN020) is a novel and potent inhibitor of aquaporin 4 (AQP4) channel (IC50: 3.1 μM), which is the most abundant water channel in the brain. It acts by increasing regional cerebral blood flow and reducing ischemia-induced brain edema. Aquaporin 4 (AQP4), the most abundant isozyme of the water specific membrane transporter aquaporin family, has now been implicated to play a significant role in the pathogenesis of various disease processes of the nervous system from epilepsy to Alzheimer's disease. Considering its clinical relevance, it is highly desirable to develop a noninvasive method for the quantitative analysis of AQP distribution in humans under clinical settings. Currently, the method of choice for such diagnostic examinations continues to be positron emission tomography (PET). Here, we report the successful development of a PET ligand for AQP4 imaging based on TGN-020, a potent AQP4 inhibitor developed previously in our laboratory. Utilizing [(11)C]-TGN-020, PET images were successfully generated in wild type and AQP4 null mice, providing a basis for future evaluation regarding its suitability for clinical studies.
| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. PROTACs selectively degrade target proteins by taking use of the intracellular ubiquitin-proteasome system[3].
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| ln Vivo |
TGN-020 (0.02 mg/μL; two microliter intravitreal injections) can reduce retinal edema in the retinas of male Wistar rats, nine weeks old, that have been given STZ to induce diabetes[2]. TGN-020 (100 mg/kg; ip; single dosage given right after SCI) decreases the degree of edema, inhibits the expression of GFAP, PCNA, and AQP4, and enhances functional recovery at days 3, 7, 14, 21, and 28 following SCI. In adult female Sprague-Dawley rats (180-220 g, 9-10 weeks old) with SCI, TGN-020 suppresses the formation of glial scars and increases the expression of GAP-43[4].
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| References |
[1]. Vincent J Huber, et al. Identification of aquaporin 4 inhibitors using in vitro and in silico methods. Bioorg Med Chem. 2009 Jan 1;17(1):411-7.
[2]. Shou Oosuka, et al. Effects of an Aquaporin 4 Inhibitor, TGN-020, on Murine Diabetic Retina. Int J Mol Sci. 2020 Mar 27;21(7):2324. [3]. An S, et al. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs. EBioMedicine. 2018 Oct;36:553-562 [4]. Jian Li, et al. TGN-020 alleviates edema and inhibits astrocyte activation and glial scar formation after spinal cord compression injury in rats. Life Sci. 2019 Apr 1;222:148-157. |
| Molecular Formula |
C8H6N4OS
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| Molecular Weight |
206.22
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| CAS # |
51987-99-6
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| Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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| SMILES |
O=C(C1=CC=CN=C1)NC2=NN=CS2
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 25 mg/mL (121.23 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (8.10 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 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 5 mg/mL (24.25 mM) in 0.5% MC 0.5% Tween-80 (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.8492 mL | 24.2460 mL | 48.4919 mL | |
| 5 mM | 0.9698 mL | 4.8492 mL | 9.6984 mL | |
| 10 mM | 0.4849 mL | 2.4246 mL | 4.8492 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.
PET images. (a) WT and (b) KO mice. |
Ex vivo PET images of the brain. (a) WT and (b) KO mouse brains. (c) MRI images of the corresponding brain slices.ACS Chem Neurosci. 2011 Oct 19; 2(10): 568–571. |
Time course analysis of SUV. Data from WT (n= 6, ○) and KO (n= 4, |
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COA
) models are shown along with the standard error of means. (a) Brain, (b) skeletal muscle, and (c) heart.