SB-203580 | CAS#152121-47-6 | p38 MAPK inhibitor

MedKoo Cat#: 555153 | Name: SB-203580

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SB-203580, also known as RWJ-64809, is a specific inhibitor of p38α and p38β which suppresses downstream activation of MAPKAP kinase-2 and heat shock protein 27. At low concentrations, it does not inhibit JNK activity. SB-203580 was recently assigned the INN Adezamapimod, and is currently in phase 2 clinical trials to prevent post-operative tissue adhesion.

Chemical Structure

SB-203580

CAS#152121-47-6 (free base)

Theoretical Analysis

MedKoo Cat#: 555153

Name: SB-203580

CAS#: 152121-47-6 (free base)

Chemical Formula: C21H16FN3OS

Exact Mass: 377.0998

Molecular Weight: 377.44

Elemental Analysis: C, 66.83; H, 4.27; F, 5.03; N, 11.13; O, 4.24; S, 8.49

Price and Availability

Size	Price	Availability
5mg	USD 250.00	Ready to ship
10mg	USD 400.00	Ready to ship
25mg	USD 750.00	Ready to ship
50mg	USD 1,150.00	Ready to ship

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Related CAS #

152121-47-6 (free base) 869185-85-3 (HCl)

Synonym

Adezmapimod; SB203850; SB-203850; SB 203850; RWJ 64809; RWJ64809; RWJ-64809;

IUPAC/Chemical Name

4-(4-Fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole

InChi Key

CDMGBJANTYXAIV-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H16FN3OS/c1-27(26)18-8-4-16(5-9-18)21-24-19(14-2-6-17(22)7-3-14)20(25-21)15-10-12-23-13-11-15/h2-13H,1H3,(H,24,25)

SMILES Code

O=S(C1=CC=C(C2=NC(C3=CC=C(F)C=C3)=C(C4=CC=NC=C4)N2)C=C1)C

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A25M02B21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SB-203580 is a selective and ATP-competitive p38 MAPK inhibitor with IC50s of 50 nM and 500 nM for SAPK2a/p38 and SAPK2b/p38β2, respectively. SB-203580 inhibits LCK, GSK3β and PKBα with IC50s of 100-500-fold higher than that for SAPK2a/p38.

In vitro activity:

In human lung adenocarcinoma (A549) cells, SB-203580 pretreatment enhanced resveratrol-induced apoptosis by accelerating the intrinsic apoptotic pathway, involving Bax activation, mitochondrial membrane potential loss, and activation of caspase-9 and -3. The combination of SB-203580 and resveratrol activated the extrinsic apoptotic pathway, marked by FasL cleavage and caspase-8 activation. This suggests a synergistic effect, providing a potential alternative therapeutic approach for human lung cancer. Reference: J Biochem Mol Toxicol. 2012 Jul;26(7):251-7. https://pubmed.ncbi.nlm.nih.gov/22644961/

In vivo activity:

In a murine model of acute long injury, SB-203580 protected against inflammatory responses and lung injury by inhibiting lung edema and downregulating proinflammatory mediators in LPS‑induced lung injury. Reference: Mol Med Rep. 2020 Aug;22(2):1656-1662. https://pubmed.ncbi.nlm.nih.gov/32626961/

	Solvent	mg/mL	mM
Solubility
	DMSO	20.0	52.99

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 377.44 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. Han X, Chen H, Zhou J, Steed H, Postovit LM, Fu Y. Pharmacological Inhibition of p38 MAPK by SB203580 Increases Resistance to Carboplatin in A2780cp Cells and Promotes Growth in Primary Ovarian Cancer Cells. Int J Mol Sci. 2018 Jul 26;19(8):2184. doi: 10.3390/ijms19082184. PMID: 30049957; PMCID: PMC6121386. 2. Li H, Wang X, Chen T, Qu J. p38 inhibitor SB203580 sensitizes the resveratrol-induced apoptosis in human lung adenocarcinoma (A549) cells. J Biochem Mol Toxicol. 2012 Jul;26(7):251-7. doi: 10.1002/jbt.21413. Epub 2012 May 29. PMID: 22644961. 3. Li G, Dai Y, Tan J, Zou J, Nie X, Yang Z, Zhao J, Yang X, Chen J. SB203580 protects against inflammatory response and lung injury in a mouse model of lipopolysaccharide‑induced acute lung injury. Mol Med Rep. 2020 Aug;22(2):1656-1662. doi: 10.3892/mmr.2020.11214. Epub 2020 Jun 4. PMID: 32626961. 4. Gao X, Li N, Zhang J. SB203580, a p38MAPK inhibitor, attenuates olfactory dysfunction by inhibiting OSN apoptosis in AR mice (activation and involvement of the p38 mitogen-activated protein kinase in olfactory sensory neuronal apoptosis of OVA-induced allergic rhinitis). Brain Behav. 2019 Jun;9(6):e01295. doi: 10.1002/brb3.1295. Epub 2019 Apr 30. PMID: 31041850; PMCID: PMC6577615.

In vitro protocol:

In vivo protocol:

1. Li G, Dai Y, Tan J, Zou J, Nie X, Yang Z, Zhao J, Yang X, Chen J. SB203580 protects against inflammatory response and lung injury in a mouse model of lipopolysaccharide‑induced acute lung injury. Mol Med Rep. 2020 Aug;22(2):1656-1662. doi: 10.3892/mmr.2020.11214. Epub 2020 Jun 4. PMID: 32626961. 2. Gao X, Li N, Zhang J. SB203580, a p38MAPK inhibitor, attenuates olfactory dysfunction by inhibiting OSN apoptosis in AR mice (activation and involvement of the p38 mitogen-activated protein kinase in olfactory sensory neuronal apoptosis of OVA-induced allergic rhinitis). Brain Behav. 2019 Jun;9(6):e01295. doi: 10.1002/brb3.1295. Epub 2019 Apr 30. PMID: 31041850; PMCID: PMC6577615.

1: Hall-Jackson CA, Goedert M, Hedge P, Cohen P. Effect of SB 203580 on the activity of c-Raf in vitro and in vivo. Oncogene. 1999 Mar 25;18(12):2047-54. doi: 10.1038/sj.onc.1202603. PMID: 10321729. 2: Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, Gallagher TF, Young PR, Lee JC. SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett. 1995 May 8;364(2):229-33. doi: 10.1016/0014-5793(95)00357-f. PMID: 7750577. 3: Nakano A, Cohen MV, Critz S, Downey JM. SB 203580, an inhibitor of p38 MAPK, abolishes infarct-limiting effect of ischemic preconditioning in isolated rabbit hearts. Basic Res Cardiol. 2000 Dec;95(6):466-71. doi: 10.1007/s003950070022. PMID: 11192367. 4: Ward KW, Prokscht JW, Azzaranot LM, Mumawa JA, Roethke TJ, Stelman GJ, Walsh MJ, Zeigler KS, McSurdy-Freed JE, Kehlert JR, Chokshi J, Levy MA, Smith BR. Preclinical pharmacokinetics of SB-203580, a potent inhibitor of p38 mitogen- activated protein kinase. Xenobiotica. 2001 Nov;31(11):783-97. doi: 10.1080/00498250110065621. PMID: 11765141. 5: Badger AM, Cook MN, Lark MW, Newman-Tarr TM, Swift BA, Nelson AH, Barone FC, Kumar S. SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes. J Immunol. 1998 Jul 1;161(1):467-73. Erratum in: J Immunol 1999 Mar 1;162(5):3105. PMID: 9647257. 6: Davies SP, Reddy H, Caivano M, Cohen P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105. doi: 10.1042/0264-6021:3510095. PMID: 10998351; PMCID: PMC1221339. 7: Kumar S, Jiang MS, Adams JL, Lee JC. Pyridinylimidazole compound SB 203580 inhibits the activity but not the activation of p38 mitogen-activated protein kinase. Biochem Biophys Res Commun. 1999 Oct 5;263(3):825-31. doi: 10.1006/bbrc.1999.1454. PMID: 10512765. 8: Badger AM, Bradbeer JN, Votta B, Lee JC, Adams JL, Griswold DE. Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function. J Pharmacol Exp Ther. 1996 Dec;279(3):1453-61. PMID: 8968371. 9: Kankaanranta H, De Souza PM, Barnes PJ, Salmon M, Giembycz MA, Lindsay MA. SB 203580, an inhibitor of p38 mitogen-activated protein kinase, enhances constitutive apoptosis of cytokine-deprived human eosinophils. J Pharmacol Exp Ther. 1999 Aug;290(2):621-8. PMID: 10411570. 10: Hasegawa M, Cahill GM. Regulation of the circadian oscillator in Xenopus retinal photoreceptors by protein kinases sensitive to the stress-activated protein kinase inhibitor, SB 203580. J Biol Chem. 2004 May 21;279(21):22738-46. doi: 10.1074/jbc.M401389200. Epub 2004 Mar 17. PMID: 15028715. 11: Shanware NP, Williams LM, Bowler MJ, Tibbetts RS. Non-specific in vivo inhibition of CK1 by the pyridinyl imidazole p38 inhibitors SB 203580 and SB 202190. BMB Rep. 2009 Mar 31;42(3):142-7. doi: 10.5483/bmbrep.2009.42.3.142. PMID: 19336000; PMCID: PMC4412876. 12: Börsch-Haubold AG, Pasquet S, Watson SP. Direct inhibition of cyclooxygenase-1 and -2 by the kinase inhibitors SB 203580 and PD 98059. SB 203580 also inhibits thromboxane synthase. J Biol Chem. 1998 Oct 30;273(44):28766-72. doi: 10.1074/jbc.273.44.28766. PMID: 9786874. 13: Guo X, Gerl RE, Schrader JW. Defining the involvement of p38alpha MAPK in the production of anti- and proinflammatory cytokines using an SB 203580-resistant form of the kinase. J Biol Chem. 2003 Jun 20;278(25):22237-42. doi: 10.1074/jbc.M300847200. Epub 2003 Mar 11. PMID: 12637577. 14: Sarker KP, Nakata M, Kitajima I, Nakajima T, Maruyama I. Inhibition of caspase-3 activation by SB 203580, p38 mitogen-activated protein kinase inhibitor in nitric oxide-induced apoptosis of PC-12 cells. J Mol Neurosci. 2000 Dec;15(3):243-50. doi: 10.1385/JMN:15:3:243. PMID: 11303787. 15: Lal AS, Clifton AD, Rouse J, Segal AW, Cohen P. Activation of the neutrophil NADPH oxidase is inhibited by SB 203580, a specific inhibitor of SAPK2/p38. Biochem Biophys Res Commun. 1999 Jun 7;259(2):465-70. doi: 10.1006/bbrc.1999.0759. PMID: 10362531. 16: Gum RJ, McLaughlin MM, Kumar S, Wang Z, Bower MJ, Lee JC, Adams JL, Livi GP, Goldsmith EJ, Young PR. Acquisition of sensitivity of stress-activated protein kinases to the p38 inhibitor, SB 203580, by alteration of one or more amino acids within the ATP binding pocket. J Biol Chem. 1998 Jun 19;273(25):15605-10. doi: 10.1074/jbc.273.25.15605. PMID: 9624152. 17: Bignante EA, Lorenzo A. APP signaling in Alzheimer's disease. Aging (Albany NY). 2018 Nov 13;10(11):3063-3064. doi: 10.18632/aging.101641. PMID: 30425187; PMCID: PMC6286822. 18: Joyeux M, Boumendjel A, Carroll R, Ribuot C, Godin-Ribuot D, Yellon DM. SB 203580, a mitogen-activated protein kinase inhibitor, abolishes resistance to myocardial infarction induced by heat stress. Cardiovasc Drugs Ther. 2000 Jun;14(3):337-43. doi: 10.1023/a:1007847111368. PMID: 10935156. 19: ten Hove T, van den Blink B, Pronk I, Drillenburg P, Peppelenbosch MP, van Deventer SJ. Dichotomal role of inhibition of p38 MAPK with SB 203580 in experimental colitis. Gut. 2002 Apr;50(4):507-12. doi: 10.1136/gut.50.4.507. PMID: 11889071; PMCID: PMC1773163. 20: Glover M, Sweeny C, Davis B, O'Shaughnessy KM. A Single Amino Acid Substitution Makes WNK4 Susceptible to SB 203580 and SB 202190. Open Med Chem J. 2010 Sep 3;4:57-61. doi: 10.2174/1874104501004010057. PMID: 21249167; PMCID: PMC3023092.