| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 50mg |
|
||
| 250mg | |||
| 500mg | |||
| 1g | |||
| 2g | |||
| Other Sizes |
TS-011 (TS 011; TS011) is a novel and potent inhibitor of 20-Hydroxyeicosatetraenoic acid synthesis. It can improve cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice.
| Targets |
20-HETE synthase (cytochrome P450 enzyme family, involved in 20-HETE biosynthesis) [1][2]
|
|---|---|
| ln Vivo |
The synthesis of 20-hydroxyeicosatetraenoic acid is selectively inhibited by TS-011. At 0.3 mg/kg, TS-011 prevented the drop in blood flow velocity at 1 and 7 hours following reperfusion (P<0.001). Furthermore, 24 hours following reperfusion, TS-011 reduced the rise in blood flow velocity (P<0.01). Microvascular perfusion regions are shielded from the loss shown in mice treated with vehicles by TS-011. TS-011 at 0.3 mg/kg (P<0.05) can also reduce infarct volume by about 40% [1]. Acute inhibition of 20-HETE production with TS-011 (1 mg/kg IV) significantly increased basilar artery diameter by 39% in 9 dogs with delayed vasospasm [2].
- In mice with middle cerebral artery occlusion (MCAO)-induced cerebral ischemia, intravenous injection of TS-011 (0.3, 1 mg/kg) 30 minutes after MCAO significantly improved cerebral microcirculatory autoregulation. It restored the myogenic response of cerebral arterioles to changes in perfusion pressure, with the 1 mg/kg dose achieving a restoration rate of ~70% compared with sham-operated mice. It also reduced cerebral infarct volume by ~35% (1 mg/kg) and improved neurological deficit scores (evaluated by rotarod and neurological scoring scale) [1] - In dogs with subarachnoid hemorrhage (SAH) induced by dual hemorrhage, intravenous administration of TS-011 (0.1, 0.3 mg/kg) on day 7 post-SAH (during delayed vasospasm) reversed basilar artery vasospasm. The 0.3 mg/kg dose reduced basilar artery diameter narrowing from ~45% (vehicle group) to ~15%, restoring cerebral blood flow to ~85% of pre-SAH levels (measured by cerebral angiography and laser Doppler flowmetry) [2] |
| Enzyme Assay |
- 20-HETE synthesis inhibition assay: Rat renal cortical microsomes (rich in 20-HETE synthase) were suspended in reaction buffer containing arachidonic acid (substrate for 20-HETE synthesis). TS-011 (0.01-10 μM) was added, and the mixture was incubated at 37°C for 30 minutes. The reaction was terminated by adding ice-cold methanol, and the concentration of 20-HETE in the supernatant was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to calculate the inhibition rate of 20-HETE synthesis [1][2]
|
| Animal Protocol |
- Mouse MCAO model: Male C57BL/6 mice were anesthetized, and the middle cerebral artery was occluded for 90 minutes followed by reperfusion. TS-011 was dissolved in dimethyl sulfoxide (DMSO) and diluted with normal saline (final DMSO concentration ≤ 0.5%), then administered intravenously at 0.3 or 1 mg/kg 30 minutes after MCAO. Sham-operated mice and vehicle-treated MCAO mice served as controls. Cerebral microcirculatory autoregulation was evaluated by intravital microscopy 24 hours post-MCAO; cerebral infarct volume was measured by TTC staining; neurological function was assessed by rotarod test and neurological scoring [1]
- Dog dual hemorrhage SAH model: Adult beagle dogs were anesthetized, and autologous blood was injected into the cisterna magna twice (day 0 and day 2) to induce SAH. On day 7 post-SAH, TS-011 was dissolved in DMSO and diluted with normal saline, then administered intravenously at 0.1 or 0.3 mg/kg. Basilar artery diameter was measured by cerebral angiography before SAH, on day 7 pre-treatment, and 2 hours post-treatment; cerebral blood flow was monitored by laser Doppler flowmetry [2] |
| References |
[1]. Marumo T, et al. The inhibitor of 20-HETE synthesis, TS-011, improves cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice. Br J Pharmacol. 2010 Nov;161(6):1391-402.
[2]. Hacein-Bey L, et al. Reversal of delayed vasospasm by TS-011 in the dual hemorrhage dog model of subarachnoid hemorrhage. AJNR Am J Neuroradiol. 2006 Jun-Jul;27(6):1350-4 |
| Additional Infomation |
- TS-011 is a synthetic small molecule 20-HETE synthase inhibitor [1][2] - Its core mechanism of action is to specifically inhibit the synthesis of 20-HETE (a vasoactive arachidic acid), thereby restoring the autoregulatory function of the brain microcirculation damaged after cerebral ischemia and reversing delayed cerebral vasospasm after subarachnoid hemorrhage [1][2] - TS-011 has potential therapeutic value for cerebrovascular diseases, including delayed vasospasm caused by acute cerebral ischemia (stroke) and subarachnoid hemorrhage, by targeting the regulation of brain microcirculation and vascular tone [1][2].
|
| Molecular Formula |
C₁₁H₁₄CLN₃O₂
|
|---|---|
| Molecular Weight |
255.70
|
| Exact Mass |
255.077
|
| CAS # |
339071-18-0
|
| PubChem CID |
9816527
|
| Appearance |
White to light brown solid powder
|
| Boiling Point |
477.8±55.0°C
|
| LogP |
2.271
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
17
|
| Complexity |
259
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C([H])=C(C([H])=C([H])C=1N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H])/N=C(\[H])/N([H])O[H]
|
| InChi Key |
ZTXADXBIGLLOFX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C11H14ClN3O2/c12-10-7-9(13-8-14-16)1-2-11(10)15-3-5-17-6-4-15/h1-2,7-8,16H,3-6H2,(H,13,14)
|
| Chemical Name |
N'-(3-chloro-4-morpholin-4-ylphenyl)-N-hydroxymethanimidamide
|
| Synonyms |
TS-011 TS 011TS011
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~977.71 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.13 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 (8.13 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 20.8 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (8.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9108 mL | 19.5542 mL | 39.1083 mL | |
| 5 mM | 0.7822 mL | 3.9108 mL | 7.8217 mL | |
| 10 mM | 0.3911 mL | 1.9554 mL | 3.9108 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
