RWJ-67657 | CAS#215303-72-3 | p38 MAPK inhibitor |

MedKoo Cat#: 510234 | Name: RWJ-67657

Description:

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

RWJ-67657 is a potent and selective inhibitor of p38 mitogen-activated protein kinase (MAPK), a key enzyme involved in pro-inflammatory cytokine production. It inhibits p38α MAPK with an IC₅₀ of approximately 50–100 nM in in vitro kinase assays. In cellular systems, RWJ-67657 suppresses the production of TNF-α and IL-1β in lipopolysaccharide (LPS)-stimulated human monocytic cells with IC₅₀ values in the low nanomolar range (about 20–50 nM). Preclinical studies have shown that RWJ-67657 has significant anti-inflammatory effects in rodent models of rheumatoid arthritis and other inflammatory conditions by reducing cytokine levels and inflammation-related tissue damage. Its pharmacological profile demonstrates good oral bioavailability and target engagement, supporting its potential as a therapeutic candidate for chronic inflammatory diseases.

Chemical Structure

RWJ-67657

CAS#215303-72-3

Theoretical Analysis

MedKoo Cat#: 510234

Name: RWJ-67657

CAS#: 215303-72-3

Chemical Formula: C27H24FN3O

Exact Mass: 425.1903

Molecular Weight: 425.50

Elemental Analysis: C, 76.21; H, 5.69; F, 4.46; N, 9.88; O, 3.76

Price and Availability

Size	Price	Availability
10mg	USD 350.00	2 Weeks
25mg	USD 550.00	2 Weeks
50mg	USD 950.00	2 Weeks
100mg	USD 1,650.00	2 Weeks
200mg	USD 2,850.00	2 Weeks

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Synonym

RWJ67657; RWJ-67657; RWJ 67657

IUPAC/Chemical Name

4-(4-(4-fluorophenyl)-1-(3-phenylpropyl)-5-(pyridin-4-yl)-1H-imidazol-2-yl)but-3-yn-1-ol

InChi Key

QSUSKMBNZQHHPA-UHFFFAOYSA-N

InChi Code

InChI=1S/C27H24FN3O/c28-24-13-11-22(12-14-24)26-27(23-15-17-29-18-16-23)31(25(30-26)10-4-5-20-32)19-6-9-21-7-2-1-3-8-21/h1-3,7-8,11-18,32H,5-6,9,19-20H2

SMILES Code

OCCC#CC1=NC(C2=CC=C(F)C=C2)=C(C3=CC=NC=C3)N1CCCC4=CC=CC=C4

Appearance

white 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 and ethanol

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

Instruction

View handling instruction

Biological target:

RWJ-67657 is a selective p38α and p38β inhibitor (IC50s = 1 and 11 μM respectively) that displays no activity at p38γ, p38δ and a range of other kinases. RWJ-67657 potently inhibits TNF-α and IL-1β release (IC50s = 3 and 11 nM respectively) and suppresses HIV-1 replication in T cells in vitro.

In vitro activity:

RWJ-67657 effectively inhibited HIV-1 replication in both T-cell and monocyte cell lines, irrespective of the coreceptor used by the virus for entry into the cell. RWJ-67657 effectively suppressed both reverse transcriptase and protease resistant escape mutant viruses. Reference: AIDS. 2004 Mar 26;18(5):739-48. https://pubmed.ncbi.nlm.nih.gov/15075508/

In vivo activity:

The pharmacological inhibition of p38 with RWJ-67657 led to a decrease in chemoresistant cancer tumor growth in xenograft animal models. This suggests that RWJ-67657 has potential therapeutic relevance in reversing epithelial-to-mesenchymal transition in advanced tumor phenotypes and overcoming drug resistance in breast cancer. Reference: Int J Oncol. 2013 Apr;42(4):1139-50. https://pubmed.ncbi.nlm.nih.gov/23403951/

	Solvent	mg/mL	mM
Solubility
	DMSO	42.6	100.00
	Ethanol	42.6	100.00

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 425.50 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. Huang KW, Wang IH, Fu P, Krum H, Bach LA, Wang BH. Insulin-like growth factor-1 directly affects cardiac cellular remodelling via distinct pathways. Int J Cardiol Heart Vasc. 2021 Aug 2;36:100852. doi: 10.1016/j.ijcha.2021.100852. PMID: 34401470; PMCID: PMC8349770. 2. Muthumani K, Wadsworth SA, Dayes NS, Hwang DS, Choo AY, Abeysinghe HR, Siekierka JJ, Weiner DB. Suppression of HIV-1 viral replication and cellular pathogenesis by a novel p38/JNK kinase inhibitor. AIDS. 2004 Mar 26;18(5):739-48. doi: 10.1097/00002030-200403260-00004. PMID: 15075508. 3. Antoon JW, Nitzchke AM, Martin EC, Rhodes LV, Nam S, Wadsworth S, Salvo VA, Elliott S, Collins-Burow B, Nephew KP, Burow ME. Inhibition of p38 mitogen-activated protein kinase alters microRNA expression and reverses epithelial-to-mesenchymal transition. Int J Oncol. 2013 Apr;42(4):1139-50. doi: 10.3892/ijo.2013.1814. Epub 2013 Feb 8. PMID: 23403951; PMCID: PMC3622654. 4. Kompa AR, See F, Lewis DA, Adrahtas A, Cantwell DM, Wang BH, Krum H. Long-term but not short-term p38 mitogen-activated protein kinase inhibition improves cardiac function and reduces cardiac remodeling post-myocardial infarction. J Pharmacol Exp Ther. 2008 Jun;325(3):741-50. doi: 10.1124/jpet.107.133546. Epub 2008 Mar 11. PMID: 18334667.

In vitro protocol:

In vivo protocol:

1. Antoon JW, Nitzchke AM, Martin EC, Rhodes LV, Nam S, Wadsworth S, Salvo VA, Elliott S, Collins-Burow B, Nephew KP, Burow ME. Inhibition of p38 mitogen-activated protein kinase alters microRNA expression and reverses epithelial-to-mesenchymal transition. Int J Oncol. 2013 Apr;42(4):1139-50. doi: 10.3892/ijo.2013.1814. Epub 2013 Feb 8. PMID: 23403951; PMCID: PMC3622654. 2. Kompa AR, See F, Lewis DA, Adrahtas A, Cantwell DM, Wang BH, Krum H. Long-term but not short-term p38 mitogen-activated protein kinase inhibition improves cardiac function and reduces cardiac remodeling post-myocardial infarction. J Pharmacol Exp Ther. 2008 Jun;325(3):741-50. doi: 10.1124/jpet.107.133546. Epub 2008 Mar 11. PMID: 18334667.

1: Wadsworth SA, Cavender DE, Beers SA, Lalan P, Schafer PH, Malloy EA, Wu W, Fahmy B, Olini GC, Davis JE, Pellegrino-Gensey JL, Wachter MP, Siekierka JJ. RWJ 67657, a potent, orally active inhibitor of p38 mitogen-activated protein kinase. J Pharmacol Exp Ther. 1999 Nov;291(2):680-7. PMID: 10525088. 2: Dos Santos BR, Ramos ABDSB, de Menezes RPB, Scotti MT, Colombo FA, Marques MJ, Reimão JQ. Anti-Toxoplasma gondii screening of MMV pandemic response box and evaluation of RWJ-67657 efficacy in chronically infected mice. Parasitology. 2023 Nov;150(13):1226-1235. doi: 10.1017/S0031182023000999. Epub 2023 Oct 20. PMID: 37859414; PMCID: PMC10941209. 3: Westra J, Limburg PC, de Boer P, van Rijswijk MH. Effects of RWJ 67657, a p38 mitogen activated protein kinase (MAPK) inhibitor, on the production of inflammatory mediators by rheumatoid synovial fibroblasts. Ann Rheum Dis. 2004 Nov;63(11):1453-9. doi: 10.1136/ard.2003.013011. PMID: 15479895; PMCID: PMC1754789. 4: Bai YY, Wang L, Chang D, Zhao Z, Lu CQ, Wang G, Ju S. Synergistic Effects of Transplanted Endothelial Progenitor Cells and RWJ 67657 in Diabetic Ischemic Stroke Models. Stroke. 2015 Jul;46(7):1938-46. doi: 10.1161/STROKEAHA.114.008495. Epub 2015 Jun 4. PMID: 26045601. 5: Parasrampuria DA, de Boer P, Desai-Krieger D, Chow AT, Jones CR. Single-dose pharmacokinetics and pharmacodynamics of RWJ 67657, a specific p38 mitogen- activated protein kinase inhibitor: a first-in-human study. J Clin Pharmacol. 2003 Apr;43(4):406-13. doi: 10.1177/0091270002250615. PMID: 12723461. 6: Faas MM, Moes H, Fijen JW, Muller Kobold AC, Tulleken JE, Zijlstra JG. Monocyte intracellular cytokine production during human endotoxaemia with or without a second in vitro LPS challenge: effect of RWJ-67657, a p38 MAP-kinase inhibitor, on LPS-hyporesponsiveness. Clin Exp Immunol. 2002 Feb;127(2):337-43. doi: 10.1046/j.1365-2249.2002.01765.x. PMID: 11876759; PMCID: PMC1906333. 7: Westra J, Doornbos-van der Meer B, de Boer P, van Leeuwen MA, van Rijswijk MH, Limburg PC. Strong inhibition of TNF-alpha production and inhibition of IL-8 and COX-2 mRNA expression in monocyte-derived macrophages by RWJ 67657, a p38 mitogen-activated protein kinase (MAPK) inhibitor. Arthritis Res Ther. 2004;6(4):R384-92. doi: 10.1186/ar1204. Epub 2004 Jun 21. PMID: 15225374; PMCID: PMC464924. 8: Westra J, Kułdo JM, van Rijswijk MH, Molema G, Limburg PC. Chemokine production and E-selectin expression in activated endothelial cells are inhibited by p38 MAPK (mitogen activated protein kinase) inhibitor RWJ 67657. Int Immunopharmacol. 2005 Jul;5(7-8):1259-69. doi: 10.1016/j.intimp.2005.03.005. Epub 2005 Apr 26. PMID: 15914330. 9: Fijen JW, Zijlstra JG, De Boer P, Spanjersberg R, Tervaert JW, Van Der Werf TS, Ligtenberg JJ, Tulleken JE. Suppression of the clinical and cytokine response to endotoxin by RWJ-67657, a p38 mitogen-activated protein-kinase inhibitor, in healthy human volunteers. Clin Exp Immunol. 2001 Apr;124(1):16-20. doi: 10.1046/j.1365-2249.2001.01485.x. PMID: 11359438; PMCID: PMC1906020. 10: Bai YY, Wang L, Peng XG, Wang YC, Chang D, Zheng S, Ding J, Li C, Ju S. Non- invasive monitoring of transplanted endothelial progenitor cells in diabetic ischemic stroke models. Biomaterials. 2015 Feb;40:43-50. doi: 10.1016/j.biomaterials.2014.11.018. Epub 2014 Nov 26. PMID: 25433605. 11: See F, Thomas W, Way K, Tzanidis A, Kompa A, Lewis D, Itescu S, Krum H. p38 mitogen-activated protein kinase inhibition improves cardiac function and attenuates left ventricular remodeling following myocardial infarction in the rat. J Am Coll Cardiol. 2004 Oct 19;44(8):1679-89. doi: 10.1016/j.jacc.2004.07.038. PMID: 15489104. 12: Fijen JW, Tulleken JE, Kobold AC, de Boer P, van der Werf TS, Ligtenberg JJ, Spanjersberg R, Zijlstra JG. Inhibition of p38 mitogen-activated protein kinase: dose-dependent suppression of leukocyte and endothelial response after endotoxin challenge in humans. Crit Care Med. 2002 Apr;30(4):841-5. doi: 10.1097/00003246-200204000-00021. PMID: 11940756. 13: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 May;25(4):317-40. PMID: 12808477. 14: Dos Santos M, Oliveira Costa AL, Vaz GHS, de Souza GCA, Vitor RWA, Martins- Duarte ÉS. Medicines for Malaria Venture Pandemic Box In Vitro Screening Identifies Compounds Highly Active against the Tachyzoite Stage of Toxoplasma gondii. Trop Med Infect Dis. 2023 Nov 29;8(12):510. doi: 10.3390/tropicalmed8120510. PMID: 38133442; PMCID: PMC10747034. 15: Kuldo JM, Westra J, Asgeirsdóttir SA, Kok RJ, Oosterhuis K, Rots MG, Schouten JP, Limburg PC, Molema G. Differential effects of NF-{kappa}B and p38 MAPK inhibitors and combinations thereof on TNF-{alpha}- and IL-1{beta}-induced proinflammatory status of endothelial cells in vitro. Am J Physiol Cell Physiol. 2005 Nov;289(5):C1229-39. doi: 10.1152/ajpcell.00620.2004. Epub 2005 Jun 22. PMID: 15972838. 16: Westra J, Bijzet J, Doornbos-van der Meer B, van Rijswijk MH, Limburg PC. Differential influence of p38 mitogen activated protein kinase (MAPK) inhibition on acute phase protein synthesis in human hepatoma cell lines. Ann Rheum Dis. 2006 Jul;65(7):929-35. doi: 10.1136/ard.2005.043232. Epub 2005 Nov 3. PMID: 16269426; PMCID: PMC1798216. 17: Thurmond RL, Wadsworth SA, Schafer PH, Zivin RA, Siekierka JJ. Kinetics of small molecule inhibitor binding to p38 kinase. Eur J Biochem. 2001 Nov;268(22):5747-54. doi: 10.1046/j.0014-2956.2001.02512.x. PMID: 11722559. 18: Lekawanvijit S, Adrahtas A, Kelly DJ, Kompa AR, Wang BH, Krum H. Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes? Eur Heart J. 2010 Jul;31(14):1771-9. doi: 10.1093/eurheartj/ehp574. Epub 2010 Jan 4. PMID: 20047993. 19: Kompa AR, See F, Lewis DA, Adrahtas A, Cantwell DM, Wang BH, Krum H. Long- term but not short-term p38 mitogen-activated protein kinase inhibition improves cardiac function and reduces cardiac remodeling post-myocardial infarction. J Pharmacol Exp Ther. 2008 Jun;325(3):741-50. doi: 10.1124/jpet.107.133546. Epub 2008 Mar 11. PMID: 18334667. 20: Kümpers P, van Meurs M, David S, Molema G, Bijzet J, Lukasz A, Biertz F, Haller H, Zijlstra JG. Time course of angiopoietin-2 release during experimental human endotoxemia and sepsis. Crit Care. 2009;13(3):R64. doi: 10.1186/cc7866. Epub 2009 May 5. PMID: 19416526; PMCID: PMC2717419.