ML3403 - CAS 549505-65-9
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Not Intended for Therapeutic Use. For research use only.
ML 3403 is a potent and selective p38 mitogen-activated protein kinase (MAPK) inhibitor. MAPK is a key mediator in cytokine-induced signaling events and plays an integral role in disease states including oncogenesis, autoimmune diseases, and inflammatory processes. Therefore, MAPK inhibitors such as ML 3403 provides an attractive strategy for therapeutic intervention.
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1.Novel p38 MAPK inhibitor ML3403 has potent anti-inflammatory activity in airway smooth muscle.
Munoz L1, Ramsay EE, Manetsch M, Ge Q, Peifer C, Laufer S, Ammit AJ. Eur J Pharmacol. 2010 Jun 10;635(1-3):212-8. doi: 10.1016/j.ejphar.2010.02.037. Epub 2010 Mar 9.
SB203580 is the prototypical p38 MAPK inhibitor; however it cannot be used clinically due to liver toxicity. We developed a structural analogue of SB203580 - ML3403 - with equal in vitro and ex vivo p38alpha MAPK inhibition as SB203580, but with reduced activity towards liver cytochrome P450 enzymes. In addition, we developed a selective p38alpha MAPK inhibitor - CP41. The aim of this study is to compare the anti-inflammatory activity of ML3403 and CP41, with SB203580. We compare and contrast the ability of the p38 MAPK inhibitors to repress tumour necrosis factor alpha (TNFalpha)-induced interleukin 6 (IL-6) and interleukin 8 (IL-8) mRNA expression and protein secretion from airway smooth muscle cells. We also examined and compared the binding affinities of ML3403 and SB203580 to the active and inactive p38alpha MAPK. We demonstrate that ML3403 binds to both active and inactive p38 MAPK with high affinity and that it inhibits p38 MAPK-mediated airway smooth muscle synthetic function to an equivalent degree with SB203580.
2.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.
Koch DA1, Silva RB, de Souza AH, Leite CE, Nicoletti NF, Campos MM, Laufer S, Morrone FB. Rheumatology (Oxford). 2014 Mar;53(3):425-32. doi: 10.1093/rheumatology/ket369. Epub 2013 Nov 15.
OBJECTIVE: Mitogen-activated protein kinase (MAPK) p38 inhibitors have entered the clinical phase, although many of them have failed due to high toxicity and lack of efficacy. In the present study we compared the effects of the selective p38 inhibitor ML3403 and the dual p38-PDE4 inhibitor CBS-3595, on inflammatory and nociceptive parameters in a model of polyarthritis in rats.
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CAS 549505-65-9 ML3403

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