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Purity: ≥98%
BMS-582949 (also known as PS540446) is a potent and highly selective p38 mitogen-activated protein kinase (p38 MAPK) inhibitor with IC50 of 13nM. It is presently undergoing phase II clinical trials for the treatment of rheumatoid arthritis. Inhibiting p38MAPK, a crucial component of the inflammatory pathways involved in atherothrombosis, may lessen inflammation within atherosclerotic plaques. Both p38 kinase activity and p38 activation are inhibited by the drug BMS-582949. By measuring p38's phosphorylation, BMS-582949 is found to inhibit p38 activation in cells. Treatment with BMS-582949 of cells in which p38 has been activated by LPS quickly reversed p38 activation, as demonstrated by loss of phosphorylation of p38. Therefore, BMS-582949 is a dual-action p38 kinase inhibitor that prevents both p38 kinase activity and p38 activation in cells.
| Targets |
p38α MAPK (IC50 = 13 nM); TNFα (IC50 = 50 nM)
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| ln Vitro |
BMS-582949 displays a p38α IC50 of 13 nM and a cellular TNFα IC50 of 50 nM[1].
BMS-582949 is a moderately weak CYP3A4 inhibitor, and BMS-582949 exhibits >2000-fold selectivity for p38α over a broad panel of 57 kinases, including serine kinases, nonreceptor tyrosine kinases, receptor tyrosine kinases, and the p38γ and δ isoforms[1]. |
| ln Vivo |
BMS-582949 (5-100 mg/kg, orally) is efficient despite having a slightly lower potency in the rat adjuvant arthritis model and the acute murine model of inflammation[1].
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| Enzyme Assay |
BMS-582949 was discovered to be 190-fold selective against Raf and 450-fold selective over Jnk2, a MAP kinase involved in inflammation. Further proof of BMS-582949's mode of binding to p38R was provided by X-ray crystallographic studies.
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| Cell Assay |
BMS-582949 inhibits p38 kinase activity as well as p38 activation. When p38 is phosphorylated, BMS-582949 is found to inhibit p38 activation in cells. As evidenced by the loss of phosphorylation of p38, BMS-582949 treatment of cells in which p38 has been activated by LPS quickly reversed p38 activation.
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| Animal Protocol |
Male Sprague-Dawley rats (250-300 g) adjuvant arthritis model[1].
1, 10, 100 mg/kg. Orally once daily (from day 11 to day 19). |
| References |
| Molecular Formula |
C₂₂H₂₇CLN₆O₂
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|---|---|---|
| Molecular Weight |
442.94
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| Exact Mass |
406.21
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| Elemental Analysis |
C, 59.66; H, 6.14; Cl, 8.00; N, 18.97; O, 7.22
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| CAS # |
912806-16-7
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| Related CAS # |
BMS-582949;623152-17-0
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| Appearance |
Solid powder
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| SMILES |
CCCNC(=O)C1=CN2C(=C1C)C(=NC=N2)NC3=C(C=CC(=C3)C(=O)NC4CC4)C.Cl
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| InChi Key |
BIYQUPNVBIOJIY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H26N6O2.ClH/c1-4-9-23-22(30)17-11-28-19(14(17)3)20(24-12-25-28)27-18-10-15(6-5-13(18)2)21(29)26-16-7-8-16;/h5-6,10-12,16H,4,7-9H2,1-3H3,(H,23,30)(H,26,29)(H,24,25,27);1H
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| Chemical Name |
4-[5-(cyclopropylcarbamoyl)-2-methylanilino]-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide;hydrochloride
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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 (5.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2576 mL | 11.2882 mL | 22.5764 mL | |
| 5 mM | 0.4515 mL | 2.2576 mL | 4.5153 mL | |
| 10 mM | 0.2258 mL | 1.1288 mL | 2.2576 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.
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