Doramapimod
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MedKoo CAT#: 200040

CAS#: 285983-48-4

Description: Doramapimod, also known as BIRB-796, is a member of the N-pyrazole-N'-naphthly urea class of p38MAPK inhibitors, which binds to the kinase with both slow association and dissociation rates. BIRB -796 has entered clinical trials for the treatment of autoimmune diseases.


Chemical Structure

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Doramapimod
CAS# 285983-48-4

Theoretical Analysis

MedKoo Cat#: 200040
Name: Doramapimod
CAS#: 285983-48-4
Chemical Formula: C31H37N5O3
Exact Mass: 527.28964
Molecular Weight: 527.66
Elemental Analysis: C, 70.56; H, 7.07; N, 13.27; O, 9.10

Price and Availability

Size Price Availability Quantity
50.0mg USD 250.0 2 weeks
100.0mg USD 450.0 2 weeks
200.0mg USD 750.0 2 weeks
500.0mg USD 1250.0 2 weeks
1.0g USD 1850.0 2 weeks
2.0g USD 2950.0 2 weeks
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Synonym: BIRB 796; BIRB796; BIRB-796; Doramapimod.

IUPAC/Chemical Name: 1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea.

InChi Key: MVCOAUNKQVWQHZ-UHFFFAOYSA-N

InChi Code: InChI=1S/C31H37N5O3/c1-22-9-11-23(12-10-22)36-29(21-28(34-36)31(2,3)4)33-30(37)32-26-13-14-27(25-8-6-5-7-24(25)26)39-20-17-35-15-18-38-19-16-35/h5-14,21H,15-20H2,1-4H3,(H2,32,33,37)

SMILES Code: O=C(NC1=C2C=CC=CC2=C(OCCN3CCOCC3)C=C1)NC4=CC(C(C)(C)C)=NN4C5=CC=C(C)C=C5

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, not in water

Shelf Life: >5 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

Preparing Stock Solutions

The following data is based on the product molecular weight 527.66 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

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1: Dietrich J, Hulme C, Hurley LH. The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of Gleevec, Nexavar, and BIRB-796. Bioorg Med Chem. 2010 Aug 1;18(15):5738-48. Epub 2010 Jun 4. PubMed PMID: 20621496.

2: Joos H, Albrecht W, Laufer S, Brenner RE. Differential effects of p38MAP kinase inhibitors on the expression of inflammation-associated genes in primary, interleukin-1beta-stimulated human chondrocytes. Br J Pharmacol. 2010 Jul;160(5):1252-62. PubMed PMID: 20590617.

3: Page TH, Brown A, Timms EM, Foxwell BM, Ray KP. p38 inhibitors suppress cytokine production in RA synovial membranes: Does variable inhibition of IL-6 production limit effectiveness in vivo? Arthritis Rheum. 2010 Jun 29. [Epub ahead of print] PubMed PMID: 20589681.

4: Namboodiri HV, Bukhtiyarova M, Ramcharan J, Karpusas M, Lee Y, Springman EB. Analysis of imatinib and sorafenib binding to p38alpha compared with c-Abl and b-Raf provides structural insights for understanding the selectivity of inhibitors targeting the DFG-out form of protein kinases. Biochemistry. 2010 May 4;49(17):3611-8. PubMed PMID: 20337484.

5: Chopra P, Kulkarni O, Gupta S, Bajpai M, Kanoje V, Banerjee M, Bansal V, Visaga S, Chatterjee M, Chaira T, Shirumalla RK, Verma AK, Dastidar SG, Sharma G, Ray A. Pharmacological profile of AW-814141, a novel, potent, selective and orally active inhibitor of p38 MAP kinase. Int Immunopharmacol. 2010 Apr;10(4):467-73. Epub 2010 Jan 20. PubMed PMID: 20093202.

6: Turpeinen T, Nieminen R, Moilanen E, Korhonen R. Mitogen-activated protein kinase phosphatase-1 negatively regulates the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in A549 human lung epithelial cells. J Pharmacol Exp Ther. 2010 Apr;333(1):310-8. Epub 2010 Jan 20. PubMed PMID: 20089808.

7: Tecle H, Feru F, Liu H, Kuhn C, Rennie G, Morris M, Shao J, Cheng AC, Gikunju D, Miret J, Coli R, Xi SH, Clugston SL, Low S, Kazmirski S, Ding YH, Cao Q, Johnson TL, Deshmukh GD, DiNitto JP, Wu JC, English JM. The design, synthesis and potential utility of fluorescence probes that target DFG-out conformation of p38alpha for high throughput screening binding assay. Chem Biol Drug Des. 2009 Dec;74(6):547-59. Epub 2009 Oct 20. PubMed PMID: 19843080.

8: Engstrom L, Pinzon-Ortiz MC, Li Y, Chen SC, Kinsley D, Nelissen R, Fine JS, Mihara K, Manfra D. Characterization of a murine keyhole limpet hemocyanin (KLH)-delayed-type hypersensitivity (DTH) model: role for p38 kinase. Int Immunopharmacol. 2009 Sep;9(10):1218-27. Epub 2009 Jul 16. PubMed PMID: 19616132.

9: Han S, Mistry A, Chang JS, Cunningham D, Griffor M, Bonnette PC, Wang H, Chrunyk BA, Aspnes GE, Walker DP, Brosius AD, Buckbinder L. Structural characterization of proline-rich tyrosine kinase 2 (PYK2) reveals a unique (DFG-out) conformation and enables inhibitor design. J Biol Chem. 2009 May 8;284(19):13193-201. Epub 2009 Feb 25. PubMed PMID: 19244237; PubMed Central PMCID: PMC2676051.

10: Genovese MC. Inhibition of p38: has the fat lady sung? Arthritis Rheum. 2009 Feb;60(2):317-20. PubMed PMID: 19180514.



Additional Information

BIRB796 inhibits the stress-activated protein kinases p38alpha and p38beta and is undergoing clinical trials for the treatment of inflammatory diseases.   However, research data showed that n o clinical efficacy (primary end point, clinical remission; secondary end point, clinical response; Inflammatory Bowel Disease Questionnaire; Crohn's Disease Endoscopic Index of Severity) was seen for BIRB 796 in comparison with placebo. A significant, dose-dependent decrease of C-reactive protein level was observed transiently after BIRB 796 after 1 week with a return to baseline level over time. The incidence of adverse events was comparable between all treatment groups, with the exception of a mild increase of transaminase levels that was seen more frequently in the BIRB 796 groups. Geographic center effects were observed with Russian centers producing distinctly higher remission and response rates and lower adverse event rates than in other countries in both placebo and active treatment groups. CONCLUSIONS: There was no evidence for clinical efficacy of BIRB 796 in CD. A remarkable difference in the course of CD exists between Russia and non-Russian centers. (source: Clin Gastroenterol Hepatol. 2006 Mar;4(3):325-34. or http://www.ncbi.nlm.nih.gov/pubmed/16527696).