STAUROSPORINE

Description

Staurosporine (Stsp) is potent inhibitor of protein kinase C (PKC) from rat brain, exhibiting an IC₅₀ value of 2.7 nM. It inhibits rat recombinant PKC-α approximately 100- and 1,000-fold better than PKC-δ and PKC-ζ, respectively. However, Stsp is non-selective in that it also inhibits the activity of a variety of other protein kinases, not only PKC isoforms. The biological effects of Stsp include cytotoxicity, relaxation of smooth muscle, and regulation of eNOS gene expression.

Chemical Properties

Light Yellow Solid

Occurrence

A complex alkaloid. staurosporine has been isolated from a strain of Streptomyces.

Uses

Staurosporine is an unusual indolocarbazole alkaloid produced by a range of actinomycete species. It is a potent antitumour active, inducing apoptosis in a variety of cell lines. Staurosporine is a potent inhibitor of many kinases including protein kinase C, tyrosine kinase, CDK2/cyclin A and CDK4/cyclin D. At submicromolar concentrations, staurosporine inhibits both IKKalpha and IKKbeta.

Uses

Staurosporine is a protein Kinase C inhibitor that induces apoptosis in many cell types.

Definition

ChEBI: Staurosporine is an indolocarbazole alkaloid and an organic heterooctacyclic compound. It has a role as an EC 2.7.11.13 (protein kinase C) inhibitor, a geroprotector, a bacterial metabolite and an apoptosis inducer. It is a conjugate base of a staurosporinium.

General Description

A potent, cell-permeable, reversible, ATP-competitive and broad spectrum inhibitor of protein kinases. Inhibits CaM kinase (IC₅₀ = 20 nM), myosin light chain kinase (IC₅₀ = 1.3 nM), protein kinase A (IC₅₀ = 7 nM), protein kinase C (IC₅₀ = 0.7 nM), and protein kinase G (IC₅₀ = 8.5 nM). Also inhibits platelet aggregation induced by collagen or ADP but has no effect on thrombin-induced platelet aggregation. Induces apoptosis in human malignant glioma cell lines. Arrests normal cells at the G₁ checkpoint.

Biological Activity

Broad spectrum protein kinase inhibitor. Enzymes inhibited include protein kinase C (IC 50 = 3 nM), protein kinase A (IC 50 = 7 nM), p 60v-src tyrosine protein kinase (IC 50 = 6 nM) and CaM kinase II (IC 50 = 20 nM). Also available as part of the Mixed Kinase Inhibitor Tocriset™ .

Biochem/physiol Actions

Reversible: yes

storage

+4°C

References

1) Omura et al. (1977) A new alkaloid AM-2282 of Streptomyces origin taxonomy, fermentation, isolation and preliminary characterization; J. Antibiot., 30 275 2) Ruegg and Burgess (1989) Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases; Trends in Pharmacological Science 10 218