Staurosporine

drugbox
IUPAC_name = ("9S,10R,11R,13R")-2,3,10,11,12,13-Hexahydro-
10-methoxy-9-methyl-11-(methylamino)-9,13-epoxy-
1"H",9"H"-diindolo [1,2,3-gh:3',2',1'-lm] pyrrolo [3,4-j] [1,7]
benzodiazonin-1-one

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CAS_number = 62996-74-1
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PubChem = 5280487
DrugBank =
C=28 | H=26 | N=4 | O=3
molecular_weight = 466.53 g/mol
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Staurosporine (antibiotic AM-2282) is a natural product originally isolated in 1977 from bacterium "Streptomyces staurosporeus".cite journal |author= Omura S, Iwai Y, Hirano A, Nakagawa A, Awaya J, Tsuchiya H, Takahashi Y, Masuma R |title= A new alkaloid AM-2282 of Streptomyces origin taxonomy, fermentation, isolation and preliminary characterization |journal= J. Antibiot. |volume= 30 |issue= 4 |pages= 275–282 |year=1977 ] It was the first of over 50 alkaloids to be isolated with this type of bis-indole chemical structure. The chemical structure of staurosporine was elucidated by X-ray analysis of a single crystal and the absolute stereochemical configuration by the same method in 1994. cite journal |author= Funato N, Takayanagi H, Konda Y, Toda Y, Harigaya Y, Omura S |title= Absolute configuration of staurosporine by X-ray analysis |journal= Tetrahedron Lett. |volume= 35 |issue= 8 |pages= 1251-1254 |year= 1994]

Staurosporine was discovered to have biological activities ranging from anti-fungal to anti-hypertensive. [ [http://www.nature.com/nbt/journal/v8/n8/abs/nbt0890-732.html] Rüegg UT, Burgess GM. (1989) Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases." Trends in Pharmacological Science" 10 (6): 218-220.] The interest in these activities resulted in a large investigative effort in chemistry and biology and the discovery of the potential for anti-cancer treatment.

The main biological activity of staurosporine is the inhibition of protein kinases through the prevention of ATP binding to the kinase. This is achieved through the stronger affinity of staurosporine to the ATP-binding site on the kinase. Staurosporine is a prototypical ATP-competitive kinase inhibitor in that it binds to many kinases with high affinity, though with little selectivity.cite journal |author= Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT, Faraoni R, Floyd M, Hunt JP, Lockhart DJ, Milanov ZV, Morrison MJ, Pallares G, Patel HK, Pritchard S, Wodicka LM, Zarrinkar PP |title= A quantitative analysis of kinase inhibitor selectivity |journal= Nat. Biotechnol. |volume= 26 |issue= 1 |pages= 127-132 |year=2008 ] This lack of specificity has precluded its clinical use, but has made it a valuable research tool.

Staurosporine is the precursor of the novel antibiotic PKC412 [ [http://www.fermentek.co.il/pkc412.htm Midostaurin] product page, Fermentek] (Midostaurin)

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