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MedKoo Cat#: 530909 | Name: Skepinone-L
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Description:

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

Skepinone-L is an ATP-competitive inhibitor of p38 MAPK isoform p38α (IC50s = 5 nM) and p38β (97% inhibition at 1 µM).

Chemical Structure

Skepinone-L
Skepinone-L
CAS#1221485-83-1

Theoretical Analysis

MedKoo Cat#: 530909

Name: Skepinone-L

CAS#: 1221485-83-1

Chemical Formula: C24H21F2NO4

Exact Mass: 425.1439

Molecular Weight: 425.43

Elemental Analysis: C, 67.76; H, 4.98; F, 8.93; N, 3.29; O, 15.04

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
10mg USD 650.00 2 Weeks
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Related CAS #
No Data
Synonym
Skepinone-L; SkepinoneL; Skepinone L;
IUPAC/Chemical Name
2-[(2,4-difluorophenyl)amino]-7-[(2R)-2,3-dihydroxypropoxy]-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one
InChi Key
HXMGCTFLLWPVFM-GOSISDBHSA-N
InChi Code
InChI=1S/C24H21F2NO4/c25-16-4-8-23(22(26)10-16)27-17-5-7-20-15(9-17)2-1-14-3-6-19(11-21(14)24(20)30)31-13-18(29)12-28/h3-11,18,27-29H,1-2,12-13H2/t18-/m1/s1
SMILES Code
O=C1C2=CC=C(NC3=CC=C(F)C=C3F)C=C2CCC4=CC=C(OC[C@H](O)CO)C=C14
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:
Skepinone-L is an ATP-competitive inhibitor of p38 MAPK isoform p38α (IC50s = 5 nM) and p38β (97% inhibition at 1 µM). It has little effect on a range of other kinases, including p38γ and p38δ. Skepinone-L dose-dependently blocks the phosphorylation of heat shock protein 27 (HSP27) in response to stimulation with anisomycin in HeLa cells (IC50 = 25 nM) or TNF-α in THP-1 cells.
In vitro activity:
Skepinone-L might provide a promising therapeutic tool to prevent inflammatory cascades in atherosclerosis. In the human leukemia cell line THP-1 and/or primary monocyte-derived macrophages, skepinone-L inhibited eLDL-induced activation of the p38 MAPK pathway, inhibited eLDL induced expression of both CD36 and ABCA1, without a net effect on foam cell formation, had a cell- and time-dependent effect on eLDL-triggered apoptosis, and inhibited eLDL-stimulated secretion of IL-8 and MIP-1β/CCL4. Reference: FASEB J. 2017 Feb;31(2):674-686. https://pubmed.ncbi.nlm.nih.gov/27871059/
In vivo activity:
Intrathecal injection of skepinone prevented formalin induced inflammatory pain in male but not female mice. Intrathecal skepinone reduced chronic constriction injury (CCI) induced neuropathic pain (mechanical allodynia) in male mice on CCI-day 7 but not CCI-day 21. This male-dependent inhibition of neuropathic pain also occurred in rats following intrathecal skepinone. Notably, intraperitoneal or local perineural administration of skepinone inhibited CCI-induced mechanical allodynia in both sexes of mice. Reference: Brain Behav Immun. 2016 Jul;55:70-81. https://pubmed.ncbi.nlm.nih.gov/26472019/
Solvent mg/mL mM comments
Solubility
DMF 20.0 47.01
DMSO 15.0 35.26
Ethanol 20.0 47.01
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 425.43 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. Cheng F, Twardowski L, Fehr S, Aner C, Schaeffeler E, Joos T, Knorpp T, Dorweiler B, Laufer S, Schwab M, Torzewski M. Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis. FASEB J. 2017 Feb;31(2):674-686. doi: 10.1096/fj.201600669R. Epub 2016 Nov 8. PMID: 27871059. 2. Taves S, Berta T, Liu DL, Gan S, Chen G, Kim YH, Van de Ven T, Laufer S, Ji RR. Spinal inhibition of p38 MAP kinase reduces inflammatory and neuropathic pain in male but not female mice: Sex-dependent microglial signaling in the spinal cord. Brain Behav Immun. 2016 Jul;55:70-81. doi: 10.1016/j.bbi.2015.10.006. Epub 2015 Oct 19. PMID: 26472019; PMCID: PMC5502100. 3. Koeberle SC, Romir J, Fischer S, Koeberle A, Schattel V, Albrecht W, Grütter C, Werz O, Rauh D, Stehle T, Laufer SA. Skepinone-L is a selective p38 mitogen-activated protein kinase inhibitor. Nat Chem Biol. 2011 Dec 25;8(2):141-3. doi: 10.1038/nchembio.761. PMID: 22198732.
In vitro protocol:
1. Cheng F, Twardowski L, Fehr S, Aner C, Schaeffeler E, Joos T, Knorpp T, Dorweiler B, Laufer S, Schwab M, Torzewski M. Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis. FASEB J. 2017 Feb;31(2):674-686. doi: 10.1096/fj.201600669R. Epub 2016 Nov 8. PMID: 27871059.
In vivo protocol:
1. Taves S, Berta T, Liu DL, Gan S, Chen G, Kim YH, Van de Ven T, Laufer S, Ji RR. Spinal inhibition of p38 MAP kinase reduces inflammatory and neuropathic pain in male but not female mice: Sex-dependent microglial signaling in the spinal cord. Brain Behav Immun. 2016 Jul;55:70-81. doi: 10.1016/j.bbi.2015.10.006. Epub 2015 Oct 19. PMID: 26472019; PMCID: PMC5502100. 2. Koeberle SC, Romir J, Fischer S, Koeberle A, Schattel V, Albrecht W, Grütter C, Werz O, Rauh D, Stehle T, Laufer SA. Skepinone-L is a selective p38 mitogen-activated protein kinase inhibitor. Nat Chem Biol. 2011 Dec 25;8(2):141-3. doi: 10.1038/nchembio.761. PMID: 22198732.
1: Koeberle SC, Romir J, Fischer S, Koeberle A, Schattel V, Albrecht W, Grütter C, Werz O, Rauh D, Stehle T, Laufer SA. Skepinone-L is a selective p38 mitogen- activated protein kinase inhibitor. Nat Chem Biol. 2011 Dec 25;8(2):141-3. doi: 10.1038/nchembio.761. PMID: 22198732. 2: Koeberle SC, Fischer S, Schollmeyer D, Schattel V, Grütter C, Rauh D, Laufer SA. Design, synthesis, and biological evaluation of novel disubstituted dibenzosuberones as highly potent and selective inhibitors of p38 mitogen activated protein kinase. J Med Chem. 2012 Jun 28;55(12):5868-77. doi: 10.1021/jm300327h. Epub 2012 Jun 15. PMID: 22676210. 3: Fischer S, Wentsch HK, Mayer-Wrangowski SC, Zimmermann M, Bauer SM, Storch K, Niess R, Koeberle SC, Grütter C, Boeckler FM, Rauh D, Laufer SA. Dibenzosuberones as p38 mitogen-activated protein kinase inhibitors with low ATP competitiveness and outstanding whole blood activity. J Med Chem. 2013 Jan 10;56(1):241-53. doi: 10.1021/jm301539x. Epub 2012 Dec 27. PMID: 23270382. 4: Borst O, Walker B, Münzer P, Russo A, Schmid E, Faggio C, Bigalke B, Laufer S, Gawaz M, Lang F. Skepinone-L, a novel potent and highly selective inhibitor of p38 MAP kinase, effectively impairs platelet activation and thrombus formation. Cell Physiol Biochem. 2013;31(6):914-24. doi: 10.1159/000350110. Epub 2013 Jun 18. PMID: 23817201. 5: Hosseinzadeh Z, Schmid E, Shumilina E, Laufer S, Borst O, Gawaz M, Lang F. Effect of TGFβ on Na+/K+ ATPase activity in megakaryocytes. Biochem Biophys Res Commun. 2014 Sep 26;452(3):537-41. doi: 10.1016/j.bbrc.2014.08.093. Epub 2014 Aug 27. PMID: 25168590. 6: Zhao ZW, Abendroth DK, Zhou ZC, Liu YZ, Pan FM, Ge JJ. Anti-inflammatory and anti-proliferative effects of CBS3830 in arterialized vein grafts in rats. Immunopharmacol Immunotoxicol. 2014 Dec;36(6):397-403. doi: 10.3109/08923973.2014.956754. Epub 2014 Sep 10. PMID: 25204222. 7: Koeberle A, Pergola C, Shindou H, Koeberle SC, Shimizu T, Laufer SA, Werz O. Role of p38 mitogen-activated protein kinase in linking stearoyl-CoA desaturase-1 activity with endoplasmic reticulum homeostasis. FASEB J. 2015 Jun;29(6):2439-49. doi: 10.1096/fj.14-268474. Epub 2015 Feb 12. PMID: 25678624. 8: Yan J, Schmid E, Almilaji A, Shumilina E, Borst O, Laufer S, Gawaz M, Lang F. Effect of TGFβ on calcium signaling in megakaryocytes. Biochem Biophys Res Commun. 2015 May 22;461(1):8-13. doi: 10.1016/j.bbrc.2015.03.159. Epub 2015 Apr 4. PMID: 25849886. 9: Taves S, Berta T, Liu DL, Gan S, Chen G, Kim YH, Van de Ven T, Laufer S, Ji RR. Spinal inhibition of p38 MAP kinase reduces inflammatory and neuropathic pain in male but not female mice: Sex-dependent microglial signaling in the spinal cord. Brain Behav Immun. 2016 Jul;55:70-81. doi: 10.1016/j.bbi.2015.10.006. Epub 2015 Oct 19. PMID: 26472019; PMCID: PMC5502100. 10: Signoretto E, Laufer SA, Lang F. Stimulating Effect of Sclareol on Suicidal Death of Human Erythrocytes. Cell Physiol Biochem. 2016;39(2):554-64. doi: 10.1159/000445647. Epub 2016 Jul 11. PMID: 27395049. 11: Cheng F, Twardowski L, Fehr S, Aner C, Schaeffeler E, Joos T, Knorpp T, Dorweiler B, Laufer S, Schwab M, Torzewski M. Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis. FASEB J. 2017 Feb;31(2):674-686. doi: 10.1096/fj.201600669R. Epub 2016 Nov 8. PMID: 27871059. 12: Wentsch HK, Walter NM, Bührmann M, Mayer-Wrangowski S, Rauh D, Zaman GJR, Willemsen-Seegers N, Buijsman RC, Henning M, Dauch D, Zender L, Laufer S. Optimized Target Residence Time: Type I1/2 Inhibitors for p38α MAP Kinase with Improved Binding Kinetics through Direct Interaction with the R-Spine. Angew Chem Int Ed Engl. 2017 May 2;56(19):5363-5367. doi: 10.1002/anie.201701185. Epub 2017 Apr 11. PMID: 28397331. 13: Al-Maghout T, Pelzl L, Sahu I, Sukkar B, Hosseinzadeh Z, Gutti R, Laufer S, Voelkl J, Pieske B, Gawaz M, Lang F. P38 Kinase, SGK1 and NF-κB Dependent Up- Regulation of Na+/Ca2+ Exchanger Expression and Activity Following TGFß1 Treatment of Megakaryocytes. Cell Physiol Biochem. 2017;42(6):2169-2181. doi: 10.1159/000479992. Epub 2017 Aug 15. PMID: 28813704. 14: Walter NM, Wentsch HK, Bührmann M, Bauer SM, Döring E, Mayer-Wrangowski S, Sievers-Engler A, Willemsen-Seegers N, Zaman G, Buijsman R, Lämmerhofer M, Rauh D, Laufer SA. Design, Synthesis, and Biological Evaluation of Novel Type I1/2 p38α MAP Kinase Inhibitors with Excellent Selectivity, High Potency, and Prolonged Target Residence Time by Interfering with the R-Spine. J Med Chem. 2017 Oct 12;60(19):8027-8054. doi: 10.1021/acs.jmedchem.7b00745. Epub 2017 Sep 7. PMID: 28834431. 15: Guenthoer P, Fuchs K, Reischl G, Quintanilla-Martinez L, Gonzalez-Menendez I, Laufer S, Pichler BJ, Kneilling M. Evaluation of the therapeutic potential of the selective p38 MAPK inhibitor Skepinone-L and the dual p38/JNK 3 inhibitor LN 950 in experimental K/BxN serum transfer arthritis. Inflammopharmacology. 2019 Dec;27(6):1217-1227. doi: 10.1007/s10787-019-00593-6. Epub 2019 Apr 29. PMID: 31037574. 16: Bhargava P, Janda J, Schnellmann RG. Elucidation of cGMP-dependent induction of mitochondrial biogenesis through PKG and p38 MAPK in the kidney. Am J Physiol Renal Physiol. 2020 Feb 1;318(2):F322-F328. doi: 10.1152/ajprenal.00533.2019. Epub 2019 Dec 16. PMID: 31841384; PMCID: PMC7052650. 17: Werner M, Pace S, Czapka A, Jordan PM, Gerstmeier J, Koeberle A, Werz O. Communication between human macrophages and epithelial cancer cell lines dictates lipid mediator biosynthesis. Cell Mol Life Sci. 2020 Nov;77(21):4365-4378. doi: 10.1007/s00018-019-03413-w. Epub 2020 Jan 1. PMID: 31894359; PMCID: PMC11104889. 18: Carrillo García C, Becker C, Forster M, Lohmann S, Freitag P, Laufer S, Sievers S, Fleischmann BK, Hesse M, Schade D. High-Throughput Screening Platform in Postnatal Heart Cells and Chemical Probe Toolbox to Assess Cardiomyocyte Proliferation. J Med Chem. 2022 Jan 27;65(2):1505-1524. doi: 10.1021/acs.jmedchem.1c01173. Epub 2021 Nov 24. PMID: 34818008. 19: Gong M, Tu M, Sun H, Li L, Zhu L, Li H, Zhao Z, Li S. Design, Synthesis, and Structure-Activity Relationship Study of Potent MAPK11 Inhibitors. Molecules. 2021 Dec 29;27(1):203. doi: 10.3390/molecules27010203. PMID: 35011435; PMCID: PMC8746797. 20: Anton DB, Galvez Bulhões Pedreira J, Zvirtes ML, Laufer SA, Ducati RG, Goettert M, Saraiva Macedo Timmers LF. Targeting SARS-CoV-2 Main Protease (MPro) with Kinase Inhibitors: A Promising Approach for Discovering Antiviral and Anti- inflammatory Molecules against SARS-CoV-2. J Chem Inf Model. 2023 Jul 10;63(13):4138-4146. doi: 10.1021/acs.jcim.3c00324. Epub 2023 Jun 17. PMID: 37329322.