Staurosporine
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| Surname | Staurosporine | ||||||||||||||||||
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| Molecular formula | C 28 H 26 N 4 O 3 | ||||||||||||||||||
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| Drug class |
Protein kinase inhibitors |
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| Molar mass | 466.53 g mol −1 | ||||||||||||||||||
| Melting point |
270 ° C (decomposition) |
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| solubility |
soluble in DMSO |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||||||||
Staurosporine is a chemical compound from the group of indolecarbazoles that effectively but unspecifically inhibits the function of kinases , a type of enzyme that transduces signals in the cell.
properties
Staurosporine was originally isolated from Streptomyces staurosporeus , but is also produced by other Streptomyces species. It has antifungal properties and acts as an antihypertensive and anticoagulant . Staurosporine is a competitive inhibitor of the binding of adenosine triphosphate to kinases. It binds in kinases to the GXGXXG motif and to the aspartate in the DFG motif .
Staurosporine is only used in research, as its effect is too unspecific for targeted therapy in certain cancers. It is used in research to induce apoptosis via caspase-3 . It also leads to the arrest of the cell cycle . It also serves as a lead structure in the development of new active ingredients, such as tetrahydrostaurosporine , a significantly more selective kinase inhibitor for cancer treatment, or the benzoyl derivative of staurosporine, midostaurine (synonym PKC412).
synthesis
Synthesis of staurosporine
Staurosporine biosynthesis
Individual evidence
- ↑ a b c Entry on staurosporine. In: Römpp Online . Georg Thieme Verlag, accessed on November 18, 2017.
- ↑ a b c Data sheet Staurosporine from Streptomyces sp., ≥98% (HPLC), film from Sigma-Aldrich , accessed on November 17, 2017 ( PDF ).
- ↑ a b MW Karaman, S. Herrgard, DK Driver, P. Gallant, CE Atteridge, BT Campbell, KW Chan, P. Ciceri, MI Davis, PT Edeen, R. Faraoni, M. Floyd, JP Hunt, DJ Lockhart, ZV Milanov, MJ Morrison, G. Pallares, HK Patel, S. Pritchard, LM Wodicka, PP Zarrinkar: A quantitative analysis of kinase inhibitor selectivity. In: Nature Biotechnology . Volume 26, Number 1, January 2008, pp. 127-132, doi: 10.1038 / nbt1358 , PMID 18183025 .
- ^ GP Ellis, DK Luscombe (Ed.): Progress in medicinal chemistry . tape 33 . Elsevier, Amsterdam 1996, ISBN 978-0-08-086281-1 , pp. 291 ( limited preview in Google Book search).
- ↑ D. Tanramluk, A. Schreyer, WR Pitt, TL Blundell: On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine. In: Chemical biology & drug design. Volume 74, number 1, July 2009, pp. 16-24, doi: 10.1111 / j.1747-0285.2009.00832.x , PMID 19519740 , PMC 2737611 (free full text).
- ↑ HJ Chae, JS Kang, JO Byun, KS Han, DU Kim, SM Oh, HM Kim, SW Chae, HR Kim: Molecular mechanism of staurosporine-induced apoptosis in osteoblasts. In: Pharmacological research. Volume 42, Number 4, October 2000, pp. 373-381, doi: 10.1006 / phrs.2000.0700 , PMID 10987998 .
- ^ S. Bruno, B. Ardelt, JS Skierski, F. Traganos, Z. Darzynkiewicz: Different effects of staurosporine, an inhibitor of protein kinases, on the cell cycle and chromatin structure of normal and leukemic lymphocytes. In: Cancer Research . Volume 52, Number 2, January 1992, pp. 470-473, PMID 1728418 .
- ^ Gerhard Klebe: Active substance design: Design and effect of medicinal substances . 2nd Edition. Spectrum Akademischer Verlag, Heidelberg 2009, ISBN 978-3-8274-2046-6 , Chapter 26: Inhibitors for transferases .
- ↑ Y. Wang, OQ Yin, P. Graf, JC Kisicki, H. Schran: Dose- and time-dependent pharmacokinetics of midostaurin in patients with diabetes mellitus. In: Journal of clinical pharmacology. Volume 48, Number 6, June 2008, pp. 763-775, doi: 10.1177 / 0091270008318006 , PMID 18508951 .
- ↑ Ryan KS: Structural studies of rebeccamycin, staurosporine, and violacein biosynthetic enzymes . In: Ph.D. Thesis . Massachusetts Institute of Technology. 2008.