Detail for staurosporine
Basic Information
DrugID 96
DrugName staurosporine
DrugDetail Staurosporine (antibiotic AM-2282 or STS) is a natural product originally isolated in 1977 from the bacterium Streptomyces staurosporeus. 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. Staurosporine was discovered to have biological activities ranging from anti-fungal to anti-hypertensive.[3] 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.[4] This lack of specificity has precluded its clinical use, but has made it a valuable research tool. In research, staurosporine is used to induce apoptosis. The mechanism of how it mediates this is not well understood. It has been found that one way in which staurosporine induces apoptosis is by activating caspase-3. Staurosporine is the precursor of the novel protein kinase inhibitor midostaurin (PKC412).Besides midostaurin, staurosporine is also used as a starting material in the commercial synthesis of K252c (also called staurosporine aglycone). In the natural biosynthetic pathway, K252c is a precursor of staurosporine.

Structure Click to see the orginal picture.
Drug Name PMIDLink Reference
Caspofungin Markovich S, Yekutiel A, Shalit I, Shadkchan Y, Osherov N. (2004) Genomic approach to identification of mutations affecting caspofungin susceptibility in Saccharomyces cerevisiae. Antimicrob Agents Chemother. 48(10):3871-6.
TargetName References EssentialGene? Link
3-phosphoinositide-dependent protein kinase 1 Yes
5'-AMP-activated protein kinase catalytic subunit alpha-1 No
70 kDa zeta-associated protein No
Activated CDC42 kinase 1 No
Agammaglobulinaemia tyrosine kinase No
Alpha-type platelet-derived growth factor receptor Yes
Aurora kinase A No
Basic fibroblast growth factor receptor 1 Yes
Beta-type platelet-derived growth factor receptor Yes
Calcium/calmodulin-dependent protein kinase type II alpha chain No
cAMP-dependent protein kinase catalytic subunit alpha No
Casein kinase I isoform gamma-2 No
Casein kinase II subunit alpha Yes
CD220 Yes
CD309 Yes
CDC-like kinase 1 No
Cell division protein kinase 2 Yes
Cell division protein kinase 4 Yes
Cell division protein kinase 5 Yes
Cell division protein kinase 6 Yes
Cell division protein kinase 9 No
c-kit Yes
Conserved helix-loop-helix ubiquitous kinase No
c-Src Yes
c-Yes No
Ephrin type-A receptor 2 No
Epidermal growth factor receptor Yes
ERK-2 Yes
FADK 1 Yes
Fibroblast growth factor receptor 2 Yes
Fibroblast growth factor receptor 3 Yes
FL cytokine receptor No
Glycogen synthase kinase-3 alpha No
Glycogen synthase kinase-3 beta Yes
Hepatocyte growth factor receptor Yes
High affinity nerve growth factor receptor Yes
I-kappa-B kinase 2 Yes
Insulin-like growth factor 1 receptor Yes
JAK-2 Yes
JAK-3 No
Kinase EMT No
MAP kinase-activated protein kinase 2 Yes
Mitogen-activated protein kinase 1 Yes
Mitogen-activated protein kinase 10 No
Mitogen-activated protein kinase 12 No
Mitogen-activated protein kinase 3 No
nPKC-epsilon No
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform No
Protein kinase C theta type No
Proto-oncogene serine/threonine-protein kinase Pim-1 No
Proto-oncogene tyrosine-protein kinase ABL1 Yes
Proto-oncogene tyrosine-protein kinase Fyn Yes
Proto-oncogene tyrosine-protein kinase LCK No
RAC-alpha serine/threonine-protein kinase Yes
Ribosomal protein S6 kinase alpha-5 No
Spleen tyrosine kinase Yes
Tyrosine-protein kinase ABL2 Yes
Tyrosine-protein kinase CSK Yes
Tyrosine-protein kinase HCK Yes
Tyrosine-protein kinase receptor FLT4 Yes
Tyrosine-protein kinase ITK/TSK No
Tyrosine-protein kinase SYK Yes
Tyrosine-protein kinase ZAP-70 No