Staurosporine
[CAS# 62996-74-1]

Identification

• Classification: API >> Antibiotics >> Other antibiotics
• Name: Staurosporine
• Synonyms: (2R,3S,4S,6S)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one
• Molecular Formula: C₂₈H₂₆N₄O₃
• Molecular Weight: 466.53
• CAS Registry Number: 62996-74-1
• EC Number: 613-127-7
• SMILES: C[C@]12[C@H]([C@H](C[C@H](O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)NC)OC

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Boiling point: 677.5±55.0 °C 760 mmHg (Calc.)^*
• Flash point: 363.6±31.5 °C (Calc.)^*
• Solubility: DMSO: 32mg/mL (Expl.)
• Index of refraction: 1.81 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H340-H350-H351-H361-H361d-H373-H410-H413
• Safety Statements: P203-P260-P264-P270-P273-P280-P301+P317-P318-P319-P330-P391-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Chronic hazardous to the aquatic environment	Aquatic Chronic	4	H413
Acute toxicity	Acute Tox.	2	H300
Flammable solids	Flam. Sol.	1	H228
Carcinogenicity	Carc.	1B	H350
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Carcinogenicity	Carc.	1A	H350
Carcinogenicity	Carc.	2	H351
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	2	H361d
Reproductive toxicity	Repr.	2	H361
Germ cell mutagenicity	Muta.	1B	H340
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Acute toxicity	Acute Tox.	2	H310

Discovery and Applications

Staurosporine is a naturally occurring alkaloid isolated from the bacterium Streptomyces staurosporeus. It is well-known as a potent and broad-spectrum inhibitor of protein kinases, a class of enzymes that regulate various cellular processes through phosphorylation of target proteins. Staurosporine’s chemical structure features an indolocarbazole framework, which contributes to its high affinity for the ATP-binding sites of many kinases.

Discovered in the late 1970s during screening of microbial metabolites for biological activity, staurosporine quickly became of interest due to its strong inhibitory effects on kinase activity. Its ability to interact with a wide range of protein kinases distinguished it as a valuable tool for studying signal transduction pathways, cellular regulation, and the role of phosphorylation in cell function.

The mechanism of action of staurosporine involves competitive inhibition at the ATP-binding pocket of kinases, thereby preventing the transfer of phosphate groups to substrate proteins. This inhibition disrupts critical signaling cascades that control cell growth, differentiation, and survival. Because of this broad-spectrum activity, staurosporine is not selective for any single kinase but affects multiple kinases across different families.

In biological research, staurosporine has been extensively used as a pharmacological tool to induce apoptosis (programmed cell death) in various cell types. By inhibiting kinases involved in survival signaling pathways, staurosporine triggers apoptotic mechanisms, making it a standard compound for investigating apoptosis regulation and pathways. This property has rendered it useful in studies related to cancer biology, neurodegeneration, and cell cycle control.

Despite its potent biological activity, staurosporine’s lack of kinase selectivity and high toxicity limit its direct therapeutic applications. However, it has served as a lead compound for the development of more selective kinase inhibitors that are used clinically. Derivatives of staurosporine have been synthesized to enhance specificity, reduce toxicity, and improve pharmacokinetic properties for potential use as anticancer and immunomodulatory agents.

Staurosporine is generally supplied as a purified compound soluble in organic solvents such as dimethyl sulfoxide (DMSO). Proper storage conditions, typically under refrigeration and protection from light, are necessary to preserve its stability and activity.

In summary, staurosporine is a microbial alkaloid that acts as a broad-spectrum inhibitor of protein kinases by competing with ATP binding. Its discovery has profoundly influenced the study of kinase signaling and apoptosis. While not used therapeutically due to toxicity, staurosporine remains an essential biochemical tool and a structural basis for designing more selective kinase inhibitors.

References

1990. Staurosporine, a potent inhibitor of C-kinase, enhances drug accumulation in multidrug-resistant cells. Biochemical and Biophysical Research Communications, 173(3).
DOI: 10.1016/s0006-291x(05)80921-0

1991. Highly synchronous culture of fibroblasts from G2 block caused by staurosporine, a potent inhibitor of protein kinases. Experimental Cell Research, 192(1).
DOI: 10.1016/0014-4827(91)90166-r

2024. Marine Staurosporine Analogues: Activity and Target Identification in Triple-Negative Breast Cancer. Marine Drugs, 22(10).
DOI: 10.3390/md22100459