Abstract
[reaction: see text] We have previously described a model of paclitaxel-microtubule binding that led to the prediction that analogues of paclitaxel lacking any D ring could stabilize microtubules as well as paclitaxel if the substituent present at C4 did not have unfavorable steric interactions with the binding pocket. We report the synthesis of a 4-methyl paclitaxel analogue, compound 1, which bears this prediction out. Compound 1 is as potent as paclitaxel at microtubule stabilization in vitro; however, it has only about one-four-hundredth the cytotoxicity of paclitaxel.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents, Phytogenic / chemical synthesis*
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Antineoplastic Agents, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / pharmacology
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Binding Sites
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Docetaxel
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Humans
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Models, Molecular
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Molecular Conformation
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Paclitaxel / analogs & derivatives*
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Paclitaxel / chemical synthesis
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Paclitaxel / chemistry
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Paclitaxel / pharmacology*
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Protein Binding
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Structure-Activity Relationship
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Taxoids / chemistry
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Tubulin Modulators
Substances
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Antineoplastic Agents, Phytogenic
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Taxoids
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Tubulin Modulators
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Docetaxel
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Paclitaxel