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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
2001-10-18
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pubmed:abstractText |
The novel anticancer compound T138067 is an irreversible inhibitor of tubulin polymerization. Amides 3-6 were synthesized using standard methodologies and determined to be significantly less lipophilic than T138067 based on logP calculations. Tubulin polymerization and [(3)H]-T138067 competition assays revealed that these amides are pro-drugs for parent aniline 2. Amides 3-5 showed no detectable signs of crossing the blood brain barrier, while amide 6 was found in extremely small amounts (12 ng/g of brain tissue). Aniline 2, which was formed in vivo from these amides, was found in significantly smaller amounts (approximately 20 to >5000 times) in the brain than when 2 was administered directly. The in vivo efficacy of amide 6 approached that of T138067 and was better tolerated when administered to athymic nude mice bearing MX-1 human mammary tumor xenografts.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BaichwalVV,
pubmed-author:BeckmannHH,
pubmed-author:ClarkD LDL,
pubmed-author:FrankmoelleWW,
pubmed-author:KIDDR ARA,
pubmed-author:RocheDD,
pubmed-author:RubensteinS MSM,
pubmed-author:SanthaEE,
pubmed-author:SchwenderSS,
pubmed-author:ThoolenMM,
pubmed-author:YuAA
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3599-605
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:11606124-Aniline Compounds,
pubmed-meshheading:11606124-Animals,
pubmed-meshheading:11606124-Antineoplastic Agents,
pubmed-meshheading:11606124-Blood-Brain Barrier,
pubmed-meshheading:11606124-Brain,
pubmed-meshheading:11606124-Drug Screening Assays, Antitumor,
pubmed-meshheading:11606124-Humans,
pubmed-meshheading:11606124-Male,
pubmed-meshheading:11606124-Mice,
pubmed-meshheading:11606124-Mice, Nude,
pubmed-meshheading:11606124-Polymers,
pubmed-meshheading:11606124-Structure-Activity Relationship,
pubmed-meshheading:11606124-Sulfonamides,
pubmed-meshheading:11606124-Transplantation, Heterologous,
pubmed-meshheading:11606124-Tubulin,
pubmed-meshheading:11606124-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Hydrophilic, pro-drug analogues of T138067 are efficacious in controlling tumor growth in vivo and show a decreased ability to cross the blood brain barrier.
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pubmed:affiliation |
Tularik Inc., Two Corporate Drive, South San Francisco, CA 94080, USA. rubenstein@tularik.com
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pubmed:publicationType |
Journal Article
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