生物活性

• 靶点

  CaMKII IC50:20nM

  PKA IC50:7nM

  PKC IC50:0.7nM

  PKG IC50:8.5nM

  v-Src (p60) IC50:6nM

• 描述Protein kinase C (PKC) is a serine/threonine protein kinase, which plays a crucial role in signaling transduction mechanisms in many cell types and tissues. Staurosporine is the first reported and widely used PKC inhibitor with IC50 value of 2.7 nM for PKC (rat brain, measured by enzyme activity assay)^[1] and also displays broadly potent across the kinome with IC50 values of 15 nM, 18 nM, 3 nM, 5 nM, 21 nM, 20 nM, 9 nM, 6 nM, 20 nM, 2 nM, 16 nM for PKA, PKG, Phosphorylase kinase, S6 kinase, MLCK, Ca²⁺/CaM PK-II, cdc2, v-Src, Lyn, c-Fgr, TPK-IIB/Syk (measured by recombinant enzyme), respectively. Staurosporine is a broad selective protein kinase inhibitor and can suppress the auto-phosphorylation of Lyn and c-Fgr in a dose-dependent manner^[2]. Staurosporine induces the translocation of PKC from the soluble to the membrane, considered as the inactivation of PKC, and causes the Inhibition of PKC activity with decreased phosphorylation of PKC substrate. The inhibition of staurosporine against PKC is Ca²⁺ dependent^[3]. Staurosporine can disturb different cell response, including neuronal function, cell growth and differentiation, cell motility, secretion and cellular metabolism and smooth muscle contraction, through inhibition of PKC^[4].
• 作用机制Staurosporine is an ATP-competitive inhibitor of PKC^[2].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  FL5.12-Akt1 cells	-	Proliferation assay	-	Antiproliferative activity against FL5.12-Akt1 cells by MTT assay, IC50=0.29 μM.	16403626
  HEK293 cells	-	Cytotoxic assay	72 h	Cytotoxicity against HEK293 cells after 72 hrs by CellTiterGlo assay, IC50=56 nM.	24763262
  HEK293 cells	-	Function assay	-	Inhibition of IL-8 release by HEK293 cells expressing PKC-beta2, IC50=77 nM.	15771419

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• 动物研究
  剂量	Rat[5] (i.v.): min = 0.1 mg/kg, max = 10 mg/kg
  给药途径	i.v.
  动物药代数据	Animal Rats[6] T1/2 51.6 min (in plasma) 75.3 min (in RBC)

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00651261	Leukemia	Phase 3	Active, not recruiting	-	-
  NCT01161550	Leukemia, Myeloid, Acute	Phase 1	Completed	-	United States, Missouri ... more >> Washington University School of Medicine St. Louis, Missouri, United States, 63110 Collapse <<
  NCT00019838	Leukemia Lymp... more >>homa Collapse <<	Phase 1	Completed	-	United States, Maryland ... more >> Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland, United States, 20892-1182 NCI - Center for Cancer Research Bethesda, Maryland, United States, 20892 Collapse <<

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• 参考文献

• [1] Tamaoki T, Nomoto H, et al. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem Biophys Res Commun. 1986 Mar 13;135(2):397-402.

  [2] Meggio F, Donella Deana A, et al. Different susceptibility of protein kinases to staurosporine inhibition. Kinetic studies and molecular bases for the resistance of protein kinase CK2. Eur J Biochem. 1995 Nov 15;234(1):317-22.

  [3] Wolf M, Baggiolini M, et al. The protein kinase inhibitor staurosporine, like phorbol esters, induces the association of protein kinase C with membranes. Biochem Biophys Res Commun. 1988 Aug 15;154(3):1273-9.

  [4] Ōmura S, Asami Y, et al. Staurosporine: new lease of life for parent compound of today's novel and highly successful anti-cancer drugs. J Antibiot (Tokyo). 2018 Aug;71(8):688-701.

  [5] Secrest RJ, Williams P, et al. Hypotensive properties of the protein kinase inhibitor, staurosporine, in normotensive and spontaneously hypertensive rats. Clin Exp Hypertens A. 1991;13(2):219-34.

  [6] Gurley LR, Umbarger KO, et al. High-performance liquid chromatographic analysis of staurosporine in vivo. Its translocation and pharmacokinetics in rats. J Chromatogr B Biomed Sci Appl. 1998 Aug 7;712(1-2):211-24.

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