BMS582949 free base
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MedKoo CAT#: 555138

CAS#: 623152-17-0 (free base)

Description: BMS-582949 is a potent and selective P38 mitogen-activated protein kinase (P38 MAPK) inhibitor. BMS-582949 is currently under Phase II clinical trials for the treatment of inflammatory diseases. One clinical study showed that, in stable atherosclerosis, 12 weeks of treatment with BMS-582949 did not reduce arterial inflammation or hs-CRP compared to placebo, whereas intensification of statin therapy significantly decreased arterial inflammation. p38α MAP kinase plays a crucial role in regulating the biosynthesis of many inflammatory cytokines including TNFα and IL-1β.

Chemical Structure

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BMS582949 free base
CAS# 623152-17-0 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 555138
Name: BMS582949 free base
CAS#: 623152-17-0 (free base)
Chemical Formula: C22H26N6O2
Exact Mass: 406.21
Molecular Weight: 406.490
Elemental Analysis: C, 65.01; H, 6.45; N, 20.68; O, 7.87

Price and Availability

Size Price Availability Quantity
5mg USD 150 Ready to ship
10mg USD 250 Ready to ship
25mg USD 450 Ready to ship
50mg USD 750 Ready to ship
100mg USD 1250 Ready to ship
200mg USD 1950 Ready to ship
500mg USD 2950 Ready to Ship
1g USD 4650 Ready to Ship
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Related CAS #: 623152-17-0 (free base)   912806-16-7 (HCl)  

Synonym: BMS582949 free base; BMS-582949; BMS 582949; BMS582949; PS-540446; PS 540446; PS540446.

IUPAC/Chemical Name: 4-((5-(cyclopropylcarbamoyl)-2-methylphenyl)amino)-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide

InChi Key: GDTQLZHHDRRBEB-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H26N6O2/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)

SMILES Code: O=C(C1=CN2N=CN=C(NC3=CC(C(NC4CC4)=O)=CC=C3C)C2=C1C)NCCC

Appearance: 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

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

More Info:

Biological target: BMS-582949 (PS540446) is a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor with IC50 of 13nM.
In vitro activity: An investigative study was conducted to evaluate the effects of BMS-582949 in rat and monkey neutrophils and monocytes in vitro. BMS-582949 inhibited phagocytosis in monkey and rat neutrophils in a dose-dependent manner (Figure 5). Phagocytosis function was significantly (p ≤ 0.05) decreased in rat and monkey neutrophils at 0.5 µM (0.2 µg/ml), 5 µM (2.1 µg/ml), and 50 µM (21 µg/ml). At 5 and 50 µM the median percent inhibitions were higher for monkeys (37 and 44%, respectively) than rats (16 and 27%, respectively). The incidence of ≥ 30% inhibition was also higher in monkeys (Table 3). The species differences in median percent inhibition and incidence of ≥ 30% inhibition are reflected in the higher IC30 values for rat (62 µM, 25 µg/ml) than monkey (23.2 µM, 9.4 µg/ml). Regardless of the group median differences between monkey and rat, there are several individual incidences of ≥ 30% inhibition of neutrophil phagocytosis observed in both monkey and rat (Table 3) at 5 µM (2.1 µg/ml) BMS-582949, which is 0.1–10× the Cmax values achieved in animals with infections. There were no BMS-582949-related effects on monocyte phagocytosis function demonstrated in monkeys or rats. Reference: J Immunotoxicol. 2013 Jan-Mar;10(1):106-17. https://www.tandfonline.com/doi/full/10.3109/1547691X.2012.736427
In vivo activity: TBD

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 48.0 118.08
DMF 30.0 73.80
DMF:PBS (pH 7.2) (1:1) 0.5 1.23
Ethanol 1.0 2.46

Preparing Stock Solutions

The following data is based on the product molecular weight 406.49 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.

Recalculate based on batch purity %
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. Freebern WJ, Bigwarfe TJ, Price KD, Haggerty HG. Methods: implementation of in vitro and ex vivo phagocytosis and respiratory burst function assessments in safety testing. J Immunotoxicol. 2013 Jan-Mar;10(1):106-17. doi: 10.3109/1547691X.2012.736427. Epub 2012 Nov 23. PMID: 23173903.
In vitro protocol: 1. Freebern WJ, Bigwarfe TJ, Price KD, Haggerty HG. Methods: implementation of in vitro and ex vivo phagocytosis and respiratory burst function assessments in safety testing. J Immunotoxicol. 2013 Jan-Mar;10(1):106-17. doi: 10.3109/1547691X.2012.736427. Epub 2012 Nov 23. PMID: 23173903.
In vivo protocol: TBD

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1: Liu C, Lin J, Hynes J, Wu H, Wrobleski ST, Lin S, Dhar TG, Vrudhula VM, Sun JH, Chao S, Zhao R, Wang B, Chen BC, Everlof G, Gesenberg C, Zhang H, Marathe PH, McIntyre KW, Taylor TL, Gillooly K, Shuster DJ, McKinnon M, Dodd JH, Barrish JC, Schieven GL, Leftheris K. Discovery of ((4-(5-(Cyclopropylcarbamoyl)-2-methylphenylamino)-5-methylpyrrolo[1,2-f][1,2,4]t riazine-6-carbonyl)(propyl)carbamoyloxy)methyl-2-(4-(phosphonooxy)phenyl)acetate (BMS-751324), a Clinical Prodrug of p38α MAP Kinase Inhibitor. J Med Chem. 2015 Sep 22. [Epub ahead of print] PubMed PMID: 26359680.

2: Saxena A, Shah D, Padmanabhan S, Gautam SS, Chowan GS, Mandlekar S, Desikan S. Prediction of pH dependent absorption using in vitro, in silico, and in vivo rat models: Early liability assessment during lead optimization. Eur J Pharm Sci. 2015 Aug 30;76:173-80. doi: 10.1016/j.ejps.2015.05.006. Epub 2015 May 8. PubMed PMID: 25960252.

3: Emami H, Vucic E, Subramanian S, Abdelbaky A, Fayad ZA, Du S, Roth E, Ballantyne CM, Mohler ER, Farkouh ME, Kim J, Farmer M, Li L, Ehlgen A, Langenickel TH, Velasquez L, Hayes W, Tawakol A. The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: a multicenter FDG-PET trial. Atherosclerosis. 2015 Jun;240(2):490-6. doi: 10.1016/j.atherosclerosis.2015.03.039. Epub 2015 Mar 28. PubMed PMID: 25913664.

4: Liu C, Lin J, Everlof G, Gesenberg C, Zhang H, Marathe PH, Malley M, Galella MA, McKinnon M, Dodd JH, Barrish JC, Schieven GL, Leftheris K. Synthesis and evaluation of carbamoylmethylene linked prodrugs of BMS-582949, a clinical p38α inhibitor. Bioorg Med Chem Lett. 2013 May 15;23(10):3028-33. doi: 10.1016/j.bmcl.2013.03.022. Epub 2013 Mar 15. PubMed PMID: 23578688.

5: Freebern WJ, Bigwarfe TJ, Price KD, Haggerty HG. Methods: implementation of in vitro and ex vivo phagocytosis and respiratory burst function assessments in safety testing. J Immunotoxicol. 2013 Jan-Mar;10(1):106-17. doi: 10.3109/1547691X.2012.736427. Epub 2012 Nov 23. PubMed PMID: 23173903.

6: Liu C, Lin J, Wrobleski ST, Lin S, Hynes J, Wu H, Dyckman AJ, Li T, Wityak J, Gillooly KM, Pitt S, Shen DR, Zhang RF, McIntyre KW, Salter-Cid L, Shuster DJ, Zhang H, Marathe PH, Doweyko AM, Sack JS, Kiefer SE, Kish KF, Newitt JA, McKinnon M, Dodd JH, Barrish JC, Schieven GL, Leftheris K. 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 Med Chem. 2010 Sep 23;53(18):6629-39. doi: 10.1021/jm100540x. PubMed PMID: 20804198.

7: Norman P. BMS-582949: crystalline form of a p38alpha inhibitor? WO2008079857. Expert Opin Ther Pat. 2009 Aug;19(8):1165-8. doi: 10.1517/13543770902816160. PubMed PMID: 19505194.