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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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ML355 is the first selective, orally bioavailable 12-LOX inhibitor which displays high potency (IC50 of 0.34 μM) against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. ML355 has favorable ADME/Pharmacokinetic properties, it inhibits PAR-4 induced aggregation and calcium mobilization in human platelets, and reduces 12-HETE in mouse/human beta cells suggesting its potential utility in animal models for antiplatelet therapy and diabetes. ML355 treatment impaired thrombus growth and vessel occlusion in FeCl3-induced mesenteric and laser-induced cremaster arteriole thrombosis models in mice.
| ln Vitro |
In addition to lowering 12-HETE in beta cells, ML355 prevents calcium mobilization and human platelet aggregation triggered by PAR-4 [1].
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| ln Vivo |
In comparison to WT controls, ML355 (1.88–30 mg/kg; ir; twice daily for two days) significantly reduces the formation of thrombus in mice at higher doses[3].
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| Animal Protocol |
Animal/Disease Models: C57BL/6 mice[3]
Doses: 1.88 , 3.75, 7.5, 15, 30 mg/kg Route of Administration: po (oral gavage); 2 times per day for two days Experimental Results: The thrombus formation in mice was strongly inhibited by higher doses of ML355. |
| References |
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| Additional Infomation |
ML355 is a sulfonamide resulting from the formal condensation of the amino group of 2-aminobenzothiazole with the sulfo group of 4-[(2-hydroxy-3-methoxybenzyl)amino]benzenesulfonic acid. It is an inhibitor of 12-lipoxygenase, being developed by Veralox Therapeutics for the treatment of heparin-induced thrombocytopenia and thrombosis. It has a role as an EC 1.13.11.31 (arachidonate 12-lipoxygenase) inhibitor and a platelet aggregation inhibitor. It is a member of benzothiazoles, a sulfonamide, a monomethoxybenzene, a member of phenols, a secondary amino compound and a substituted aniline. It is functionally related to a 2-aminobenzothiazole.
12-Lipoxygenase Inhibitor VLX-1005 is a selective small molecule inhibitor of 12-lipoxygenase (12-LOX), with potential anti-platelet and anti-thrombotic activities. Upon intravenous administration, 12-LOX inhibitor VLX-1005 inhibits platelet 12-LOX. This modulates Fc gamma receptor IIa (FcgRIIa; CD32a) signaling, inhibits FcgRIIa-mediated platelet activation and aggregation, and reduces thrombus formation. The activation of the FcgRIIa receptor plays an important role in immune-mediated thrombosis, such as heparin-induced thrombocytopenia (HIT). 12-LOX, an enzyme expressed in platelets, regulates FcgRIIa activity in the platelet. |
| Molecular Formula |
C21H19N3O4S2
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| Molecular Weight |
441.52
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| Exact Mass |
441.081
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| CAS # |
1532593-30-8
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| Related CAS # |
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| PubChem CID |
70701426
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| Appearance |
White to gray solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
654.5±65.0 °C at 760 mmHg
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| Flash Point |
349.6±34.3 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.725
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| LogP |
3.95
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
651
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OWHBVKBNNRYMIN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H19N3O4S2/c1-28-18-7-4-5-14(20(18)25)13-22-15-9-11-16(12-10-15)30(26,27)24-21-23-17-6-2-3-8-19(17)29-21/h2-12,22,25H,13H2,1H3,(H,23,24)
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| Chemical Name |
N-(1,3-benzothiazol-2-yl)-4-[(2-hydroxy-3-methoxyphenyl)methylamino]benzenesulfonamide
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| Synonyms |
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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: ≥ 2.5 mg/mL (5.66 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 (5.66 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 25.0 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: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. Solubility in Formulation 5: 15mg/kg inDMSO:Solutol:PEG400:water; 5:10:20:65 |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2649 mL | 11.3245 mL | 22.6490 mL | |
| 5 mM | 0.4530 mL | 2.2649 mL | 4.5298 mL | |
| 10 mM | 0.2265 mL | 1.1325 mL | 2.2649 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.
Arterioscler Thromb Vasc Biol.2017 Oct;37(10):1828-1839. |
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ML355 inhibits human platelet aggregation induced by various agonists. Arterioscler Thromb Vasc Biol.2017 Oct;37(10):1828-1839. |
ML355 potently inhibits platelet function ex vivo under arterial shear. Arterioscler Thromb Vasc Biol.2017 Oct;37(10):1828-1839. |
ML355 treatment inhibited the formation of an occlusive thrombus in mesenteric artery in vivo.Arterioscler Thromb Vasc Biol.2017 Oct;37(10):1828-1839. |
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ML355 inhibition of thrombus formation requires platelet 12(S)-lipoxygenase (12-LOX).
ML355 treatment did not impair hemostatic plug formation in laser ablation saphenous vein hemostasis model.Arterioscler Thromb Vasc Biol.2017 Oct;37(10):1828-1839. |
ML355 treatment did not significantly increase bleeding as assessed by plasma extravasation after laser-induced rupture of cremaster microvasculature and tail-bleeding assays.
Platelet 12(S)-lipoxygenase (12-LOX) inhibition impairs thrombus formation in laser-induced cremaster arteriole thrombosis models.Arterioscler Thromb Vasc Biol.2017 Oct;37(10):1828-1839. |
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