Steroidal derived acids as inhibitors of human Cdc25A protein phosphatase

A group of steroidal derived acids were synthesized and found to be human Cdc25A inhibitors. Their potency ranged from 1.1 to > 100 microM; the best ones compare very favorably with that of the novel cyano-containing 5,6-seco-cholesteryl acid 1 (IC50=2.2microM) reported by us recently (Peng, H.;...

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Published in:Bioorganic & medicinal chemistry 2000-02, Vol.8 (2), p.299-306
Main Authors: HAIRUO PENG, WENGE XIE, KIM, D.-I, ZALKOW, L. H, POWIS, G, OTTERNESS, D. M, ABRAHAM, R. T
Format: Article
Language:English
Subjects:
Acids
Antineoplastic agents
Biological and medical sciences
cdc25 Phosphatases - antagonists & inhibitors
Chemotherapy
Drug Screening Assays, Antitumor
Enzyme Inhibitors - pharmacology
Humans
Medical sciences
Pharmacology. Drug treatments
Recombinant Proteins - antagonists & inhibitors
Spectrum Analysis
Steroids - chemistry
Steroids - pharmacology
Tumor Cells, Cultured
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Summary:A group of steroidal derived acids were synthesized and found to be human Cdc25A inhibitors. Their potency ranged from 1.1 to > 100 microM; the best ones compare very favorably with that of the novel cyano-containing 5,6-seco-cholesteryl acid 1 (IC50=2.2microM) reported by us recently (Peng, H.; Zalkow, L. H.; Abraham, R. T.; Powis, G. J. Med. Chem. 1998, 41, 4677). Structure-activity relationships of these compounds revealed that a hydrophobic cholesteryl side chain and a free carboxyl group are crucial for activity. The distance between these two pharmacophores is also important for the potency of these compounds. Several of the compounds showed selective growth inhibition effects in the NCI in vitro cancer cell line panel.
ISSN:0968-0896
DOI:10.1016/S0968-0896(99)00284-9