Herbimycins

The ansa-chain of the ansamycins streptovaricins (4), rifamycins (263), geldanamycin (4), and herbimycin (32) has been shown to be polyketide in origin, being made up of propionate and acetate units with the 0-methyl groups coming from methionine. The remaining aromatic C N portion of the ansamacroHdes is derived from 3-amino-5-hydroxybenzoic acid (264—266) which is formed via shikimate precursors. Based on the precursors of the rifamycins and streptovaricins isolated from mutant bacteria strains, a detailed scheme for the biosynthesis of most of the ansamacroHdes has been proposed (95,263). 

Fujio Y, Yamada F, Takahashi K, Shibata N. Responses of smooth muscle cells to platelet-derived growth factor are inhibited by herbimycin-A tyrosine kinase inhibitor. Biochem Biophys Res Commun 1993 195(1) 79—83. 

The tyrosine kinase inhibitors genistein [4—50pM dissolved in 0.05% dimethyl sulfoxide (DMSO), 30 minutes] and herbimycin (500 pM dissolved in 0.05%i DMSO, 30 minutes) are described as being useful inhibitors of caveolae uptake (61,62), which can be applied to discriminate this pathway from clathrin-mediated uptake (63). It should be questioned if a block of the enzyme affects the uptake via caveolae uptake selectively. However, genistein is thought to inhibit the receptor-induced formation of caveolae (18). As for herbimycin, no comment can be given on its selectivity. 

The following inhibiting agents are often used NEM, the PI-3 kinase inhibitors wortmannin and LY294002, filipin, nocodazole, colchicine, cyto-chalasin D, and the tyrosine kinase inhibitors herbimycin and genistein (all described above). 

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,... 

A significant breakthrough in identifying protein clients of Hsp90 was the realization that the chaperone is inhibited by benzoquinone ansamycins like geldanamycin and Herbimycin A (Whitesell et al. 1994). The first... 

Sakagami, M., P. Morrison, and W. J. Welch. Benzoquinoid ansamycins (herbimycin A and geldanamycin) interfere with the maturation of growth factor receptor tyrosine kinases. Cell Stress Chaperones. 4 19-28.1999. 

Sepp-Lorenzino, L., Z. Ma, D. E. Lebwohl, A. Vinitsky, and N. Rosen. Herbimycin A induces the 20 S proteasome- and ubiquitin-dependent degradation of receptor tyrosine kinases. J Biol Chem. 270 16580-7.1995. 

Several derivatives of herbimycin A have been prepared that possess greater antitumor activity than the parent. 

Matsumura C, Kuwashima H, Soma S, Kimura T. 2007. Effects of genistein and herbimycin, tyrosine kinase inhibitors, on catecholamine release in bovine adrenal chromaffin cells. Auton Autacoid Pharmacol 27 181-187. 

S Omura, Y Iwai, Y Takahashi, N Sadakane, A Nakagawa, H Oiwa, Y Hasegawa, T Ikai. Herbimycin, a new antibiotic produced by a strain of Streptomyces. J Anti-biot 32 255-261, 1979. 

YUehara, HFukazawa. Use and selectivity of herbimycin A as inhibitor of protein-tyrosine kinases. Meth Enzymol 201 370-379, 1991. 

Takahashi M, Berk BC. Mitogen activated protein kinase (ERK1/2) activation by shear stress and adhesion in endothelial cells. Essential role for a herbimycin-sensitive kinase. J Clin Invest. 1996 98 2623-2631. 

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