Synonym
ML3403; ML-3403; ML 3403.
IUPAC/Chemical Name
4-(5-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-4-yl)-N-(1-phenylethyl)pyridin-2-amine
InChi Key
VXPWQNBKEIVYIS-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H21FN4S/c1-15(16-6-4-3-5-7-16)26-20-14-18(12-13-25-20)22-21(27-23(28-22)29-2)17-8-10-19(24)11-9-17/h3-15H,1-2H3,(H,25,26)(H,27,28)
SMILES Code
CC(NC1=NC=CC(C2=C(C3=CC=C(F)C=C3)NC(SC)=N2)=C1)C4=CC=CC=C4
Appearance
white solid powder
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, not in water
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:
ML3403 is a potent p38 MAPK inhibitor with an IC50 of 0.38 μM.
In vitro activity:
To test the effects of p38 MAPK inhibitors on E. granulosus larvae, this study employed ML3403 and examined the phosphorylation status of Egp38. After treatment with 60 μM ML3403 for 4 hr, the phospho-Egp38 band nearly disappeared, while the phospho-Egp38 band in the control group, with or without DMSO, was clearly present (Fig. 7B); thus, the p38 MAPK inhibitor effectively blocked Egp38 phosphorylation activity in the parasite.
Reference: Korean J Parasitol. 2016 Dec;54(6):759-768. https://pubmed.ncbi.nlm.nih.gov/28095661/
In vivo activity:
To investigate the molecular mechanism underlying the up-regulation of host resistance induced by PP, this study performed an oligonucleotide microarray analysis on RNA of blood cells (hemocytes) and fat body tissues of silkworm larvae injected with active PP. Pretreatment of silkworm larvae with ML3403, a pharmacologic p38 MAPK inhibitor, suppressed the PP-dependent induction of cecropin A and moricin genes in the fat body.
Reference: J Biol Chem. 2010 Sep 10;285(37):28635-42. https://pubmed.ncbi.nlm.nih.gov/20622022/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMSO |
40.5 |
100.00 |
|
| Ethanol |
20.2 |
50.00 |
|
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
404.51
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. Lü G, Li J, Zhang C, Li L, Bi X, Li C, Fan J, Lu X, Vuitton DA, Wen H, Lin R. Molecular Cloning and Characterization of a P38-Like Mitogen-Activated Protein Kinase from Echinococcus granulosus. Korean J Parasitol. 2016 Dec;54(6):759-768. doi: 10.3347/kjp.2016.54.6.759. Epub 2016 Dec 31. PMID: 28095661; PMCID: PMC5266364.
2. Munoz L, Ramsay EE, Manetsch M, Ge Q, Peifer C, Laufer S, Ammit AJ. Novel p38 MAPK inhibitor ML3403 has potent anti-inflammatory activity in airway smooth muscle. Eur J Pharmacol. 2010 Jun 10;635(1-3):212-8. doi: 10.1016/j.ejphar.2010.02.037. Epub 2010 Mar 9. PMID: 20226180.
3. Koch DA, Silva RB, de Souza AH, Leite CE, Nicoletti NF, Campos MM, Laufer S, Morrone FB. Efficacy and gastrointestinal tolerability of ML3403, a selective inhibitor of p38 MAP kinase and CBS-3595, a dual inhibitor of p38 MAP kinase and phosphodiesterase 4 in CFA-induced arthritis in rats. Rheumatology (Oxford). 2014 Mar;53(3):425-32. doi: 10.1093/rheumatology/ket369. Epub 2013 Nov 15. PMID: 24241037.
4. Ishii K, Hamamoto H, Kamimura M, Nakamura Y, Noda H, Imamura K, Mita K, Sekimizu K. Insect cytokine paralytic peptide (PP) induces cellular and humoral immune responses in the silkworm Bombyx mori. J Biol Chem. 2010 Sep 10;285(37):28635-42. doi: 10.1074/jbc.M110.138446. Epub 2010 Jul 9. PMID: 20622022; PMCID: PMC2937889.
In vitro protocol:
1. Lü G, Li J, Zhang C, Li L, Bi X, Li C, Fan J, Lu X, Vuitton DA, Wen H, Lin R. Molecular Cloning and Characterization of a P38-Like Mitogen-Activated Protein Kinase from Echinococcus granulosus. Korean J Parasitol. 2016 Dec;54(6):759-768. doi: 10.3347/kjp.2016.54.6.759. Epub 2016 Dec 31. PMID: 28095661; PMCID: PMC5266364.
2. Munoz L, Ramsay EE, Manetsch M, Ge Q, Peifer C, Laufer S, Ammit AJ. Novel p38 MAPK inhibitor ML3403 has potent anti-inflammatory activity in airway smooth muscle. Eur J Pharmacol. 2010 Jun 10;635(1-3):212-8. doi: 10.1016/j.ejphar.2010.02.037. Epub 2010 Mar 9. PMID: 20226180.
In vivo protocol:
1. Koch DA, Silva RB, de Souza AH, Leite CE, Nicoletti NF, Campos MM, Laufer S, Morrone FB. Efficacy and gastrointestinal tolerability of ML3403, a selective inhibitor of p38 MAP kinase and CBS-3595, a dual inhibitor of p38 MAP kinase and phosphodiesterase 4 in CFA-induced arthritis in rats. Rheumatology (Oxford). 2014 Mar;53(3):425-32. doi: 10.1093/rheumatology/ket369. Epub 2013 Nov 15. PMID: 24241037.
2. Ishii K, Hamamoto H, Kamimura M, Nakamura Y, Noda H, Imamura K, Mita K, Sekimizu K. Insect cytokine paralytic peptide (PP) induces cellular and humoral immune responses in the silkworm Bombyx mori. J Biol Chem. 2010 Sep 10;285(37):28635-42. doi: 10.1074/jbc.M110.138446. Epub 2010 Jul 9. PMID: 20622022; PMCID: PMC2937889.
1: Koch DA, Silva RB, de Souza AH, Leite CE, Nicoletti NF, Campos MM, Laufer S, Morrone FB. Efficacy and gastrointestinal tolerability of ML3403, a selective inhibitor of p38 MAP kinase and CBS-3595, a dual inhibitor of p38 MAP kinase and phosphodiesterase 4 in CFA-induced arthritis in rats. Rheumatology (Oxford). 2013 Nov 15. [Epub ahead of print] PubMed PMID: 24241037.
2: Munoz L, Ramsay EE, Manetsch M, Ge Q, Peifer C, Laufer S, Ammit AJ. Novel p38 MAPK inhibitor ML3403 has potent anti-inflammatory activity in airway smooth muscle. Eur J Pharmacol. 2010 Jun 10;635(1-3):212-8. doi: 10.1016/j.ejphar.2010.02.037. Epub 2010 Mar 9. PubMed PMID: 20226180.
3: Kammerer B, Scheible H, Zurek G, Godejohann M, Zeller KP, Gleiter CH, Albrecht W, Laufer S. In vitro metabolite identification of ML3403, a 4-pyridinylimidazole-type p38 MAP kinase inhibitor by LC-Qq-TOF-MS and LC-SPE-cryo-NMR/MS. Xenobiotica. 2007 Mar;37(3):280-97. PubMed PMID: 17624026.
4: Kammerer B, Scheible H, Albrecht W, Gleiter CH, Laufer S. Pharmacokinetics of ML3403 ({4-[5-(4-fluorophenyl)-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-(1-pheny lethyl)-amine), a 4-Pyridinylimidazole-type p38 mitogen-activated protein kinase inhibitor. Drug Metab Dispos. 2007 Jun;35(6):875-83. Epub 2007 Mar 7. PubMed PMID: 17344341.
