erbstatin and Neoplasms

erbstatin has been researched along with Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for erbstatin and Neoplasms

ArticleYear
Induction of cellular differentiation and apoptosis by signal transduction inhibitors.
    Advances in enzyme regulation, 1997, Volume: 37

    We have isolated signal transduction inhibitors of low molecular weight from microorganisms and plants. Since inducers of differentiation and apoptosis may be developed as new anticancer agents, we have studied induction of differentiation and apoptosis in neoplastic cells by our signal transduction inhibitors. Aristeromycin isolated as an Abl function inhibitor induced erythroid differentiation in human CML K562 cells. Aristeromycin may induce differentiation by inhibition of methylating reactions in the cell. We isolated dephostatin from Streptomyces as a tyrosine phosphatase inhibitor, and synthesized its stable analogue, 3,4-dephostatin. The stable analogue, 3,4-dephostatin, potentiated NGF-induced morphological differentiation in rat pheochromocytoma PC12h cells, possibly by inhibition of tyrosine dephosphorylation of MAPK. Erbstatin, a tyrosine kinase inhibitor, induced morphological apoptosis and internucleosomal DNA fragmentation in mouse leukemia L1210 and human SCLC cells. Erbstatin was shown to induce apoptosis by hydrogen peroxide formation. Thus, these signal transduction inhibitors appear to be useful tools for the mechanistic study of cellular differentiation and apoptosis.

    Topics: Adenosine; Animals; Antineoplastic Agents; Apoptosis; Cell Differentiation; Cell Division; Formycins; Gene Expression Regulation, Neoplastic; Genes, abl; Humans; Hydroquinones; Molecular Structure; Neoplasms; Protein Tyrosine Phosphatases; Signal Transduction; Tubercidin; Tumor Cells, Cultured

1997
Protein-tyrosine kinases: potential targets for anticancer drug development.
    Stem cells (Dayton, Ohio), 1994, Volume: 12, Issue:1

    Protein-tyrosine kinases (PTKs) were originally discovered over a decade ago as the dominant transforming components of certain tumor viruses. Since then these enzymes have become recognized as important intracellular mediators of a variety of mitogenic signaling pathways, including those associated with several growth factor receptors. The strong correlation of aberrant or over-expressed PTKs with a number of proliferative diseases has raised the possibility that PTK inhibitors may afford new approaches toward anticancer therapeutics. To address this possibility, potent and specific PTK inhibitors are needed both as pharmacological probes to study PTK-dependent signaling and as potential antiproliferative agents in their own right. De novo design of PTK inhibitors is hampered by a lack of three dimensional information regarding PTKs or the interaction of inhibitors with the enzymes. Motifs for the design of new inhibitors are therefore frequently derived by modification of structural them identified in natural-product screens. Exemplary of this process is the Laboratory of Medicinal Chemistry's program to develop PTK inhibitors based on pharmacophores present in three natural-product PTK inhibitors: lavendustin A, erbstatin and piceatannol. As summarized in this report, such efforts have led to new inhibitors with increased potency and interkinase selectivity. Whether PTK inhibitors will ultimately prove to be useful as antiproliferative therapeutics remains an open question whose answer will be heavily reliant on a cooperative partnership among natural-product and medicinal chemists, pharmacologists and clinicians.

    Topics: Drug Design; Humans; Hydroquinones; Neoplasms; Phenols; Phosphotyrosine; Protein-Tyrosine Kinases; Signal Transduction; Tyrosine

1994