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MedKoo Cat#: 200040 | Name: Doramapimod
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Description:

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

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

Doramapimod
Doramapimod
CAS#285983-48-4 (free base)

Theoretical Analysis

MedKoo Cat#: 200040

Name: Doramapimod

CAS#: 285983-48-4 (free base)

Chemical Formula: C31H37N5O3

Exact Mass: 527.2896

Molecular Weight: 527.67

Elemental Analysis: C, 70.56; H, 7.07; N, 13.27; O, 9.10

Price and Availability

Size Price Availability Quantity
50mg USD 400.00 2 weeks
100mg USD 600.00 2 Weeks
250mg USD 1,000.00 2 weeks
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Related CAS #
285983-48-4 (free base) 1283526-53-3 (HCl)
Synonym
Doramapimod; BIRB 796; BIRB796; BIRB-796;
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
CC1=CC=C(C=C1)N2C(=CC(=N2)C(C)(C)C)NC(=O)NC3=CC=C(C4=CC=CC=C43)OCCN5CCOCC5
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
More Info
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).       
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Doramapimod (BIRB 796) is an orally active, highly potent p38 MAPK inhibitor, which has an IC50 for p38α=38 nM, for p38β=65 nM, for p38γ=200 nM, and for p38δ=520 nM.
In vitro activity:
These results showed that BIRB796 could reverse ABCB1-mediated MDR in both the drug selected and transfected ABCB1-overexpressing cell models, but did not enhance the efficacy of substrate-chemotherapeutical agents in ABCC1 or ABCG2 overexpression cells and their parental sensitive cells. Furthermore, BIRB796 increased the intracellular accumulation of the ABCB1 substrates, such as rhodamine 123 and doxorubicin. Moreover, BIRB796 bidirectionally mediated the ATPase activity of ABCB1, stimulating at low concentration, inhibiting at high concentration. Reference: PLoS One. 2013;8(1):e54181. https://pubmed.ncbi.nlm.nih.gov/23349819/
In vivo activity:
The beta-myosin heavy chain expression of BIRB796-treated rat hearts was significantly lower in BIRB796 compared with dTGRs, indicating a delayed switch to the fetal isoform. BIRB796 treatment significantly reduced cardiac fibrosis, connective tissue growth factor, tumor necrosis factor-alpha, interleukin-6, and macrophage infiltration. Reference: Hypertension. 2007 Mar;49(3):481-9. https://pubmed.ncbi.nlm.nih.gov/17224470/
Solvent mg/mL mM
Solubility
DMF 25.0 47.38
DMSO 53.4 0.10
Ethanol 18.2 34.42
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 527.67 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. Moon SH, Choi SW, Kim SH. In vitro anti-osteoclastogenic activity of p38 inhibitor doramapimod via inhibiting migration of pre-osteoclasts and NFATc1 activity. J Pharmacol Sci. 2015 Nov;129(3):135-42. doi: 10.1016/j.jphs.2015.06.008. Epub 2015 Jul 3. PMID: 26232862. 2. He D, Zhao XQ, Chen XG, Fang Y, Singh S, Talele TT, Qiu HJ, Liang YJ, Wang XK, Zhang GQ, Chen ZS, Fu LW. BIRB796, the inhibitor of p38 mitogen-activated protein kinase, enhances the efficacy of chemotherapeutic agents in ABCB1 overexpression cells. PLoS One. 2013;8(1):e54181. doi: 10.1371/journal.pone.0054181. Epub 2013 Jan 18. PMID: 23349819; PMCID: PMC3548808. 3. Park JK, Fischer R, Dechend R, Shagdarsuren E, Gapeljuk A, Wellner M, Meiners S, Gratze P, Al-Saadi N, Feldt S, Fiebeler A, Madwed JB, Schirdewan A, Haller H, Luft FC, Muller DN. p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage. Hypertension. 2007 Mar;49(3):481-9. doi: 10.1161/01.HYP.0000256831.33459.ea. Epub 2007 Jan 15. PMID: 17224470. 4. Kuma Y, Sabio G, Bain J, Shpiro N, Márquez R, Cuenda A. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J Biol Chem. 2005 May 20;280(20):19472-9. doi: 10.1074/jbc.M414221200. Epub 2005 Mar 8. PMID: 15755732.
In vitro protocol:
1. Moon SH, Choi SW, Kim SH. In vitro anti-osteoclastogenic activity of p38 inhibitor doramapimod via inhibiting migration of pre-osteoclasts and NFATc1 activity. J Pharmacol Sci. 2015 Nov;129(3):135-42. doi: 10.1016/j.jphs.2015.06.008. Epub 2015 Jul 3. PMID: 26232862. 2. He D, Zhao XQ, Chen XG, Fang Y, Singh S, Talele TT, Qiu HJ, Liang YJ, Wang XK, Zhang GQ, Chen ZS, Fu LW. BIRB796, the inhibitor of p38 mitogen-activated protein kinase, enhances the efficacy of chemotherapeutic agents in ABCB1 overexpression cells. PLoS One. 2013;8(1):e54181. doi: 10.1371/journal.pone.0054181. Epub 2013 Jan 18. PMID: 23349819; PMCID: PMC3548808.
In vivo protocol:
1. Park JK, Fischer R, Dechend R, Shagdarsuren E, Gapeljuk A, Wellner M, Meiners S, Gratze P, Al-Saadi N, Feldt S, Fiebeler A, Madwed JB, Schirdewan A, Haller H, Luft FC, Muller DN. p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II-induced target organ damage. Hypertension. 2007 Mar;49(3):481-9. doi: 10.1161/01.HYP.0000256831.33459.ea. Epub 2007 Jan 15. PMID: 17224470. 2. Kuma Y, Sabio G, Bain J, Shpiro N, Márquez R, Cuenda A. BIRB796 inhibits all p38 MAPK isoforms in vitro and in vivo. J Biol Chem. 2005 May 20;280(20):19472-9. doi: 10.1074/jbc.M414221200. Epub 2005 Mar 8. PMID: 15755732.
1: Bauquier J, Tudor E, Bailey S. Effect of the p38 MAPK inhibitor doramapimod on the systemic inflammatory response to intravenous lipopolysaccharide in horses. J Vet Intern Med. 2020 Sep;34(5):2109-2116. doi: 10.1111/jvim.15847. Epub 2020 Jul 23. PMID: 32700419; PMCID: PMC7517855. 2: Moon SH, Choi SW, Kim SH. In vitro anti-osteoclastogenic activity of p38 inhibitor doramapimod via inhibiting migration of pre-osteoclasts and NFATc1 activity. J Pharmacol Sci. 2015 Nov;129(3):135-42. doi: 10.1016/j.jphs.2015.06.008. Epub 2015 Jul 3. PMID: 26232862. 3: Suplatov D, Kopylov K, Sharapova Y, Švedas V. Human p38α mitogen-activated protein kinase in the Asp168-Phe169-Gly170-in (DFG-in) state can bind allosteric inhibitor Doramapimod. J Biomol Struct Dyn. 2019 May;37(8):2049-2060. doi: 10.1080/07391102.2018.1475260. Epub 2018 Dec 5. PMID: 29749295. 4: Bauquier JR, Tennent-Brown BS, Tudor E, Bailey SR. Anti-inflammatory effects of a p38 MAP kinase inhibitor, doramapimod, against bacterial cell wall toxins in equine whole blood. Vet Immunol Immunopathol. 2020 Feb;220:109994. doi: 10.1016/j.vetimm.2019.109994. Epub 2019 Dec 17. PMID: 31877483. 5: Raymonda MH, Ciesla JH, Monaghan M, Leach J, Asantewaa G, Smorodintsev- Schiller LA, Lutz MM 4th, Schafer XL, Takimoto T, Dewhurst S, Munger J, Harris IS. Pharmacologic profiling reveals lapatinib as a novel antiviral against SARS- CoV-2 in vitro. Virology. 2022 Jan;566:60-68. doi: 10.1016/j.virol.2021.11.008. Epub 2021 Nov 27. PMID: 34871905; PMCID: PMC8626825. 6: Chen S, Zhang J, Shen M, Han X, Li S, Hu C, Wang W, Li L, Du L, Pang D, Tao K, Jin A. p38 inhibition enhances TCR-T cell function and antagonizes the immunosuppressive activity of TGF-β. Int Immunopharmacol. 2021 Sep;98:107848. doi: 10.1016/j.intimp.2021.107848. Epub 2021 Jun 11. PMID: 34126342. 7: Sampson A, Peterson BG, Tan KW, Iram SH. Doxorubicin as a fluorescent reporter identifies novel MRP1 (ABCC1) inhibitors missed by calcein-based high content screening of anticancer agents. Biomed Pharmacother. 2019 Oct;118:109289. doi: 10.1016/j.biopha.2019.109289. Epub 2019 Aug 8. PMID: 31401398. 8: Zhang MZ, Liu YF, Ding L, Li ZJ, Li YZ, Si LB, Yu NZ, Wang XJ, Long X. 2-Methoxyestradiol inhibits the proliferation level in keloid fibroblasts through p38 in the MAPK/Erk signaling pathway. J Cosmet Dermatol. 2023 May 15. doi: 10.1111/jocd.15810. Epub ahead of print. PMID: 37190848. 9: Su RC, Breidenbach JD, Alganem K, Khalaf FK, French BW, Dube P, Malhotra D, McCullumsmith R, Presloid JB, Wooten RM, Kennedy DJ, Haller ST. Microcystin-LR (MC-LR) Triggers Inflammatory Responses in Macrophages. Int J Mol Sci. 2021 Sep 14;22(18):9939. doi: 10.3390/ijms22189939. PMID: 34576099; PMCID: PMC8472269. 10: Hölscher C, Gräb J, Hölscher A, Müller AL, Schäfer SC, Rybniker J. Chemical p38 MAP kinase inhibition constrains tissue inflammation and improves antibiotic activity in Mycobacterium tuberculosis-infected mice. Sci Rep. 2020 Aug 12;10(1):13629. doi: 10.1038/s41598-020-70184-x. PMID: 32788581; PMCID: PMC7423948. 11: Zhang C, Huang C, Xia H, Xu H, Tang Q, Bi F. Autophagic sequestration of SQSTM1 disrupts the aggresome formation of ubiquitinated proteins during proteasome inhibition. Cell Death Dis. 2022 Jul 15;13(7):615. doi: 10.1038/s41419-022-05061-8. PMID: 35840557; PMCID: PMC9287315. 12: Genovese MC. Inhibition of p38: has the fat lady sung? Arthritis Rheum. 2009 Feb;60(2):317-20. doi: 10.1002/art.24264. PMID: 19180514. 13: af Gennäs GB, Mologni L, Ahmed S, Rajaratnam M, Marin O, Lindholm N, Viltadi M, Gambacorti-Passerini C, Scapozza L, Yli-Kauhaluoma J. Design, synthesis, and biological activity of urea derivatives as anaplastic lymphoma kinase inhibitors. ChemMedChem. 2011 Sep 5;6(9):1680-92. doi: 10.1002/cmdc.201100168. Epub 2011 Jun 30. PMID: 21721129. 14: Kurtz SE, Eide CA, Kaempf A, Long N, Bottomly D, Nikolova O, Druker BJ, McWeeney SK, Chang BH, Tyner JW, Agarwal A. Associating drug sensitivity with differentiation status identifies effective combinations for acute myeloid leukemia. Blood Adv. 2022 May 24;6(10):3062-3067. doi: 10.1182/bloodadvances.2021006307. PMID: 35078224; PMCID: PMC9131911. 15: Soverini S, Iacobucci I, Baccarani M, Martinelli G. Targeted therapy and the T315I mutation in Philadelphia-positive leukemias. Haematologica. 2007 Apr;92(4):437-9. doi: 10.3324/haematol.11248. PMID: 17488653. 16: Ma J, Gao Z, Liu X. DDX46 accelerates the proliferation of glioblastoma by activating the MAPK-p38 signaling. J BUON. 2021 Sep-Oct;26(5):2084-2089. PMID: 34761620. 17: Cusack KP, Wang Y, Hoemann MZ, Marjanovic J, Heym RG, Vasudevan A. Design strategies to address kinetics of drug binding and residence time. Bioorg Med Chem Lett. 2015;25(10):2019-27. doi: 10.1016/j.bmcl.2015.02.027. Epub 2015 Mar 5. PMID: 25782745. 18: Browne AJ, Göbel A, Thiele S, Hofbauer LC, Rauner M, Rachner TD. p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells. Cell Death Dis. 2016 Feb 25;7(2):e2119. doi: 10.1038/cddis.2016.32. PMID: 26913608; PMCID: PMC4849158. 19: Wang J, Li J, Cao N, Li Z, Han J, Li L. Resveratrol, an activator of SIRT1, induces protective autophagy in non-small-cell lung cancer via inhibiting Akt/mTOR and activating p38-MAPK. Onco Targets Ther. 2018 Nov 2;11:7777-7786. doi: 10.2147/OTT.S159095. PMID: 30464525; PMCID: PMC6223384. 20: Wang L, Li X, Bu T, Wu X, Li L, Gao S, Yun D, Zhang Y, Chen H, Sun F, Cheng CY. Cadmium-induced Sertoli Cell Injury Through p38-MAPK and Related Signaling Proteins-A Study by RNA Sequencing. Endocrinology. 2023 Apr 17;164(6):bqad045. doi: 10.1210/endocr/bqad045. PMID: 36928142.