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Metabolic activation and cytotoxicity of 4-ipomeanol in human non-small cell lung cancer lines.

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In the normal lungs of many animal species, 4-ipomeanol is transformed to a highly reactive metabolite preferentially in pulmonary bronchiolar Clara cells and to a lesser extent in alveolar type II cells, potentially leading to damage or destruction of these cell types. Since Clara cells and type II

4-Ipomeanol: a novel investigational new drug for lung cancer.

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4-Ipomeanol (IPO) is the first agent to undergo preclinical development at the National Cancer Institute (NCI) based principally on a specific biochemical-biological rationale for clinical investigation as an antineoplastic agent targeted against lung cancer. This disease-specific development of IPO

Preclinical toxicology studies of 4-ipomeanol: a novel candidate for clinical evaluation in lung cancer.

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4-Ipomeanol (ipomeanol) is being developed as a potential antitumor agent to treat lung cancer. Ipomeanol produced a dose-related toxicity in CD2F1 mice, Fischer 344 rats, and beagle dogs. The LD50 in mice after a single iv dose of ipomeanol was 35 mg/kg in males and 26 mg/kg in females. Minimal

Phase I study of a five-day dose schedule of 4-Ipomeanol in patients with non-small cell lung cancer.

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The mammalian pulmonary toxin 4-ipomeanol (IPO) is activated by the cytochrome P450 system in bronchial Clara cells in animals. The resulting metabolites bind rapidly to macromolecules, producing localized cytotoxicity. IPO has in vitro and in vivo antitumor activity in non-small cell lung cancer

Phase I and pharmacological study of the pulmonary cytotoxin 4-ipomeanol on a single dose schedule in lung cancer patients: hepatotoxicity is dose limiting in humans.

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4-Ipomeanol (IPO), a naturally occurring pulmonary toxin, is the first cytotoxic agent to undergo clinical development based on a biochemical-biological rationale as an antineoplastic agent targeted specifically against lung cancer. This rationale is based on preclinical observations that metabolic

Acute effects of 4-ipomeanol on experimental lung tumors with bronchiolar or alveolar cell features in Syrian hamsters or C3H/HeNCr mice.

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4-Ipomenaol (IPO) has been shown to induce P-450-mediated necrosis of Clara cells in experimental animals, and clinical trials were initiated to treat people with bronchioloalveolar cancers with this novel drug. We therefore performed experiments to examine two different animal lung tumor models for

Metabolic activation of 4-ipomeanol in human lung, primary pulmonary carcinomas, and established human pulmonary carcinoma cell lines.

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4-Ipomeanol (IPO) is a pulmonary-specific toxin that is metabolically activated by a cytochrome P450 pathway in lung tissue. In this study, IPO metabolism, as determined by measurement of [14C]IPO covalent binding, was evaluated in a diverse sampling of 18 established, human lung cancer cell lines

Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone pulmonary metabolism and tumorigenicity in mice by analogues of the investigational chemotherapeutic drug 4-ipomeanol.

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4-Ipomeanol (IPO) is an investigational chemotherapeutic drug with specific toxicity toward the lung. It is metabolically activated to reactive intermediates by cytochrome P450 enzymes present in Clara cells. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a highly carcinogenic

Phase II study of 4-ipomeanol, a naturally occurring alkylating furan, in patients with advanced hepatocellular carcinoma.

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OBJECTIVE 4-Ipomeanol (IPO; NSC 394438), a naturally occurring furan isolated from common sweet potatoes (Ipomoea batatas) infected with the fungus Fusarium solani was the first agent to be developed by the National Cancer Institute based on a biochemical-biological rationale as an anticancer agent

Metabolic basis for the pulmonary Clara cell as a target for pulmonary carcinogenesis.

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The furan compound, 4-ipomeanol, is activated in lung tissue by cytochrome P-450 dependent oxidation to a highly reactive, electrophilic product that binds covalently to tissue macromolecules. Although the reactive metabolite(s) of 4-ipomeanol have not yet been definitively identified, recent

Ipomeanol analogs as chemopreventive agents: effect on the in vitro metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific, powerful, organospecific lung carcinogen. 4-Ipomeanol (IPO) is an investigational chemotherapeutic drug with specific toxicity towards the lung. We hypothesized that non-toxic analogs of IPO could be competitive inhibitors

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