Synonym
ML355; ML 355; ML-355.
IUPAC/Chemical Name
N-2-benzothiazolyl-4-[[(2-hydroxy-3-methoxyphenyl)methyl]amino]-benzenesulfonamide
InChi Key
OWHBVKBNNRYMIN-UHFFFAOYSA-N
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)
SMILES Code
O=S(C1=CC=C(NCC2=CC=CC(OC)=C2O)C=C1)(NC3=NC4=CC=CC=C4S3)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
ML355 is a potent and selective inhibitor of 12-Lipoxygenase (12-LOX) with an IC50 of 0.34 μM.
In vitro activity:
Here, this study showed that ML355 inhibited platelet activation induced by thrombin or thromboxane A2, but not by collagen-related peptide. ML355 blocked protein kinase B, phosphoinositide 3-kinase, and extracellular signal-regulated kinase, but not p38 kinase, spleen tyrosine kinase (Syk), or phospholipase Cγ2 phosphorylation in activated platelets. The main inhibitory effect of low doses of ML355 (1-20 μM) on thrombin activated platelets was mediated by the decrease in reactive oxygen species level, whereas high doses of ML355 (50 μM) caused cyclic adenosine monophosphate activation.
Reference: J Pharmacol Exp Ther. 2022 May;381(2):164-175. https://pubmed.ncbi.nlm.nih.gov/35197320/
In vivo activity:
To assess if the ALOX-12 inhibitor ML355 has any therapeutic potential, in vivo studies in mice were initiated. ML355 was administered to mice 30 minutes before GEN injection. Mice receiving GEN had cytolysis and vacuolization of epithelia, with loss of tubular brush border, as compared with control mice (Figure 9, A, B, and L). With concomitant administration of ML355, the normal morphology of tubular epithelia was largely restored and had features similar to the control (Figure 9, A, C, and L). Interestingly, some of the other renal functional parameters, such as urinary protein excretion, were also restored to normal with attenuation of albuminuria following ML355 treatment (Figure 9K).
Reference: JCI Insight. 2022 Mar 22;7(6):e155487. https://pubmed.ncbi.nlm.nih.gov/35315361/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
1.0 |
2.26 |
|
| DMSO |
43.7 |
98.90 |
|
| DMSO:PBS (pH 7.2) (1:3) |
0.3 |
0.57 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
441.52
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Shpakova V, Rukoyatkina N, Al Arawe N, Prilepskaya A, Kharazova A, Sharina I, Gambaryan S, Martin E. ML355 Modulates Platelet Activation and Prevents ABT-737 Induced Apoptosis in Platelets. J Pharmacol Exp Ther. 2022 May;381(2):164-175. doi: 10.1124/jpet.121.000973. Epub 2022 Feb 23. PMID: 35197320; PMCID: PMC9073945.
2. Ma K, Xiao A, Park SH, Glenn L, Jackson L, Barot T, Weaver JR, Taylor-Fishwick DA, Luci DK, Maloney DJ, Mirmira RG, Imai Y, Nadler JL. 12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets. J Clin Endocrinol Metab. 2017 Aug 1;102(8):2789-2797. doi: 10.1210/jc.2017-00267. PMID: 28609824; PMCID: PMC5546865.
3. Sharma I, Liao Y, Zheng X, Kanwar YS. Modulation of gentamicin-induced acute kidney injury by myo-inositol oxygenase via the ROS/ALOX-12/12-HETE/GPR31 signaling pathway. JCI Insight. 2022 Mar 22;7(6):e155487. doi: 10.1172/jci.insight.155487. PMID: 35315361; PMCID: PMC8986073.
4. He H, Adili R, Liu L, Hong K, Holinstat M, Schwendeman A. Synthetic high-density lipoproteins loaded with an antiplatelet drug for efficient inhibition of thrombosis in mice. Sci Adv. 2020 Dec 4;6(49):eabd0130. doi: 10.1126/sciadv.abd0130. PMID: 33277254; PMCID: PMC7821904.
In vitro protocol:
1. Shpakova V, Rukoyatkina N, Al Arawe N, Prilepskaya A, Kharazova A, Sharina I, Gambaryan S, Martin E. ML355 Modulates Platelet Activation and Prevents ABT-737 Induced Apoptosis in Platelets. J Pharmacol Exp Ther. 2022 May;381(2):164-175. doi: 10.1124/jpet.121.000973. Epub 2022 Feb 23. PMID: 35197320; PMCID: PMC9073945.
2. Ma K, Xiao A, Park SH, Glenn L, Jackson L, Barot T, Weaver JR, Taylor-Fishwick DA, Luci DK, Maloney DJ, Mirmira RG, Imai Y, Nadler JL. 12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets. J Clin Endocrinol Metab. 2017 Aug 1;102(8):2789-2797. doi: 10.1210/jc.2017-00267. PMID: 28609824; PMCID: PMC5546865.
In vivo protocol:
1. Sharma I, Liao Y, Zheng X, Kanwar YS. Modulation of gentamicin-induced acute kidney injury by myo-inositol oxygenase via the ROS/ALOX-12/12-HETE/GPR31 signaling pathway. JCI Insight. 2022 Mar 22;7(6):e155487. doi: 10.1172/jci.insight.155487. PMID: 35315361; PMCID: PMC8986073.
2. He H, Adili R, Liu L, Hong K, Holinstat M, Schwendeman A. Synthetic high-density lipoproteins loaded with an antiplatelet drug for efficient inhibition of thrombosis in mice. Sci Adv. 2020 Dec 4;6(49):eabd0130. doi: 10.1126/sciadv.abd0130. PMID: 33277254; PMCID: PMC7821904.
1: Luci D, Jameson JB II, Yasgar A, Diaz G, Joshi N, Kantz A, Markham K, Perry S, Kuhn N, Yeung J, Schultz L, Holinstat M, Nadler J, Taylor-Fishwick DA, Jadhav A, Simeonov A, Holman TR, Maloney DJ. Discovery of ML355, a Potent and Selective Inhibitor of Human 12-Lipoxygenase. 2013 Apr 12 [updated 2014 Sep 18]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available from http://www.ncbi.nlm.nih.gov/books/NBK259188/ PubMed PMID: 25506969.
