Of staurosporine

Ping L, Kimihiro M, Tohru Y, Yasushi O. Nardosinone, the first enhancer of neurite outgrowth-promoting activity of staurosporine and dibutyryl cyclic AMP in PCI 2D cells. Dev Brain Res 2003 145 177-183. 

Fig. 2.5 Concentrations of staurosporine in eluate fractions obtained in sequential CPC spin column/HPLC ESI-MS experiments. Mixtures of compounds were spiked with staurosporine and incubated with PKA (-A-) and without PKA (-o-) as a control. The first eluate fraction shows the most significant ligand concentration difference between the protein-ligand and control samples. Reprinted from reference [16] with permission from Elsevier Science.

In 2006, Greis and co-workers reported on the application of MALDI-TOF MS as a tool for rapid inhibitor screening [10]. Different kinases (protein kinase C-a, cAMP-dependent protein kinase) in combination with their substrates were assayed, and the inhibitory potencies of staurosporine and three novel compounds were determined. For all four compounds, IC50 values could be determined, and... 

Protein Kinase Inhibitors Pseudosubstrate-based peptide inhibitors, 201, 287 utilization of the inhibitor protein of adenosine cyclic monophosphate-dependent protein kinase, and peptides derived from it, as tools to study adenosine cyclic monophosphate-mediated cellular processes, 201, 304 use of sphingosine as inhibitor of protein kinase C, 201, 316 properties and use of H-series compounds as protein kinase inhibitors, 201, 328 use and specificity of staurosporine, UCN-01, and calphostin C as protein kinase inhibitors, 201, 340 inhibition of protein-tyrosine kinases by tyrphostins, 201, 347 use and specificity of genistein as inhibitor of protein-tyrosine kinases, 201, 362 use and selectivity of herbimycin a as inhibitor of protein-tyrosine kinases,... 

Budworth J, Davis R, Malkhandi J, Gant TW, Ferry DR, Gescher A (1996) Comparison of staurosporine and four analogues their effects on growth, rhodamine 123 retention and binding to P-glycoprotein in multidrug-resistant MCF-7/Adr cells. Br J Cancer 73 1063-1068... 

Caravatti G, Meyer T, Fredenhagen A, Trinks U, Mett H, Fabbro D (1994) Inhibitory activity and selectivity of staurosporine derivatives towards protein kinase C. Bioorg Med Chem Lett 4 399-404... 

Courage C, Snowden R, Gescher A (1996) Differential effects of staurosporine analogs on cell cycle, growth and viability in A549 cells. Br J Cancer 74 1199-1205... 

Courage C, Bradder SM, Jones T, Schultze-Mosgau MH, Gescher A (1997) Characterisation of novel human lung carcinoma cell lines selected for resistance to anti-neoplastic analogues of staurosporine. Int J Cancer 73 763-768... 

Gescher A (1998) Analogs of staurosporine Potential anticancer drugs Gen Phar-mac 31 721-728... 

Harkin ST, Cohen GM, Gescher A (1998) Modulation of apoptosis in rat thymocytes by analogs of staurosporine lack of direct association with inhibition of protein kinase C. Mol Pharmacol 54 663-670... 

Meyer T, Regenass U, Fabbro D, Alter E, Rdsel J, Muller M, Carvatti G, Matter A (1989) A derivative of staurosporine (CGP 41251) shows selectivity for PKC inhibition and in vitro antiprolif erative as well as in vivo antitumor activity. Int J Cancer,43 851-856... 

Shimizu E, Zhao MR, Nakanishi H, Yamamoto A, Yoshida S, Takada M, Ogura T, Sone S (1996) Differing effects of staurosporine and UCN-01 on RB protein phosphorylation and expression of lung cancer cell lines. Oncology 53 494-504... 

The UV spectrum [Amax 243, 267 (sh), 292, 322 (sh), 335, 356, and 372 nm] of (+)-staurosporine (AM-2282) (295) was very similar to that of staurosporinone (293), indicating the presence of a similar indolo[2,3-fl]pyrrolo[3,4-c]carbazole framework. The IR spectrum indicated the presence of an NH band at v ax 3500 cm and an amide band at 1675 cm . The structure and relative stereochemistry of this isolate were established by X-ray crystallographic analysis of the methanol solvate (282,283). The structure 295, indicating the presence of an indolocarbazole subunit, wherein two... 

In 1989, Tanida et al. reported the isolation of a 10-methoxy derivative of staurosporine, TAN-999 (296) from the culture broths of Nocardiopsis dassonvillei C-71425 in its optically active form [a]o +42.0 (c 0.50, DME). This isolate functions as a macrophage activator, useful for the treatment of mycosis, bacterial infection, and cancer (291,292). 

The UV 242, 291, 320, 334, 354, and 370 nm) and IR 1670 and 3400 cm ) spectra of 4 -N-methyl-5 -hydroxystaurosporine (300) were very similar to those of (+)-staurosporine (295) (see Scheme 2.74), indicating the presence of a similar indolo[2,3-fl]carbazole framework with a lactam function. The NMR spectra of 4 -N-methyl-5 -hydroxystaurosporine (300) were also very similar to those of (+)-staurosporine (295) (see Scheme 2.74), except for the difference in the substitution pattern of the sugar moiety. Thus, the H-NMR spectrum showed two shielded N-methyl singlets at 2.37 and a doublet (/=9.9Hz) for the C-5 proton at 4.43 and the C-3 singlet at 5 3.95, and a shielded doublet (/=9.9 Hz) for the C-4 proton at 5 3.02, indicating the presence of additional methyl and hydroxy groups at the C-4 N-methyl and the C-5 carbon, respectively. Based on these spectral data, and the structural similarity to (+)-staurosporine (295), the structure 300 was assigned to 4 -N-methyl-5 -hydroxystaurosporine. This structure was further supported by the C-NMR and NOESY spectra (298) (Scheme 2.75). 

The IR (Vmax 1685 and 3450 cm ) spectrum of N-methylstaurosporine (308) was similar to that of 4 -N -methyl-5 -hydroxystaurosporine (300) (see Scheme 2.75), indicating the presence of a similar indolo[2,3-fl]carbazole framework with a lactam function (300). The H-NMR spectrum of N-methylstaurosporine (308) was very similar to that of (+)-staurosporine (295), except for a broad methyl signal at 6 2.94 corresponding to two N-methyl groups. Based on these spectral data, and the... 

In 1989, Tanida et al. reported the isolation of the oxime analog of staurosporine, TAN-1030A (313) from culture broth of Streptomyces sp. C-71799, along with previously known (+)-staurosporine (295) (see Scheme 2.74) (291). In 1995, Cai et al. also reported TAN-1030A (313) from a different Streptomyces sp., S. longisporoflavus R19 strain (301). TAN-1030A (313) was shown to activate macrophage function in mice (291). 

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