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| | BMS-582949 (hydrochloride) Basic information |
| Product Name: | BMS-582949 (hydrochloride) | | Synonyms: | BMS-582949 (hydrochloride);BMS 582949,BMS 582949 hydrochloride,Inhibitor,BMS582949,Autophagy,BMS-582949,inhibit,BMS582949 hydrochloride,p38 MAPK;BMS-582949 hydrochloride, 10 mM in DMSO;4-((5-(Cyclopropylcarbamoyl)-2-methylphenyl)amino)-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide hydrochloride | | CAS: | 912806-16-7 | | MF: | C22H27ClN6O2 | | MW: | 442.94178 | | EINECS: | | | Product Categories: | | | Mol File: | 912806-16-7.mol |  |
| | BMS-582949 (hydrochloride) Chemical Properties |
| storage temp. | Store at -20°C | | solubility | ≥44.3 mg/mL in DMSO with gentle warming; insoluble in H2O; ≥2.7 mg/mL in EtOH with gentle warming and ultrasonic | | form | solid | | color | White to off-white |
| | BMS-582949 (hydrochloride) Usage And Synthesis |
| Uses | BMS-582949 hydrochloride is an orally active and highly selective p38α MAPK inhibitor, with an IC50 of 13 nM. BMS-582949 hydrochloride displays a significantly improved pharmacokinetic profile and is effective in inflammatory disease[1]. | | Biological Activity | bms-582949 hydrochloride is a novel, potent and highly selective p38α mitogen-activated protein kinase (p38α mapk) inhibitor [1].the p38α map kinase plays a critical role in regulating the production of many inflammatory cytokines, including tnf-α and il-1β. excessive production of tnf-α and il-1β has been implicated in many inflammatory diseases [1].bms-582949 hydrochloride potently inhibited the activity of p38α mapk with the ic50 value of 13 nm [1]. bms-582949 showed no significant effects on cytochrome p450 isozymes 1a2, 2c9, 2c19, and 2d6 with the ic50 values of >40 μm. bms-582949 weakly inhibited the activity of cyp3a4, with the ic50 value of 18-40 μm. bms-582949 displayed >2000-fold selectivity for p38α over a diverse panel of 57 kinases, include serine kinases, receptor tyrosine kinases, nonreceptor tyrosine kinases, and the p38γ and δ isoforms. bms-582949 showed 450-fold selectivity over jnk2, a map kinase involved in inflammation, and 190-fold selective over raf [1]. in mice, after oral administration of bms-582949 (10 mg/kg), the clearance rate for bms-582949 is 4.4 ml/min/kg. bms-582949 exhibited oral bioavailability values of 90% and 60% in mice and rats, respectively [1].bms-582949 is currently under phase ii | | in vivo | BMS-582949 (5-100 mg/kg, orally) is effective in both the acute murine model of inflammation and rat adjuvant arthritis model despite its slightly reduced potency[1]. | Animal Model: | Male Sprague-Dawley rats (250-300 g) adjuvant arthritis model[1]. | | Dosage: | 1, 10, 100 mg/kg. | | Administration: | Orally once daily (from day 11 to day 19). | | Result: | Displayed dose-dependent reduction in paw swelling with qd dosing, with efficacy observed at doses of 10 and 100 mg/kg. |
| | IC 50 | p38α MAPK: 13 nM (IC50); TNFα: 50 nM (IC50, in cells) | | references | [1] liu c, lin j, wrobleski s t, et al. discovery of 4-(5-(cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-n-propylpyrrolo [1, 2-f][1, 2, 4] triazine-6-carboxamide (bms-582949), a clinical p38α map kinase inhibitor for the treatment of inflammatory diseases[j]. journal of medicinal chemistry, 2010, 53(18): 6629-6639.
[2] emami h, vucic e, subramanian s, et al. the effect of bms-582949, a p38 mitogen-activated protein kinase (p38 mapk) inhibitor on arterial inflammation: a multicenter fdg-pet trial[j]. atherosclerosis, 2015, 240(2): 490-496. |
| | BMS-582949 (hydrochloride) Preparation Products And Raw materials |
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