Studies on the mechanism of phosphatidylinositol 3-kinase inhibition by wortmannin and related analogs

Journal of Medicinal Chemistry

Volumn 39, Issue 5, 1996, Pages 1106-1111

  Norman, Bryan H ^a   Shih, Chuan ^a   Toth, John E ^a   Ray, James E ^a   Dodge, Jeffrey A ^a   Johnson, Doug W ^a   Rutherford, Pamela G ^a   Schultz, Richard M ^a   Worzalla, John F ^a   Vlahos, Chris J ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

17BETA HYDROXYWORTMANNIN; PHOSPHATIDYLINOSITOL 3 KINASE; UNCLASSIFIED DRUG; WORTMANNIN;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER; CANCER CHEMOTHERAPY; DRUG MECHANISM; ENZYME INHIBITION; ENZYME PURIFICATION; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANDROSTADIENES; ANIMALS; ANTINEOPLASTIC AGENTS; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; HUMANS; MAMMARY NEOPLASMS, EXPERIMENTAL; MICE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; NEOPLASM TRANSPLANTATION; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); STRUCTURE-ACTIVITY RELATIONSHIP; THERMODYNAMICS; TUMOR CELLS, CULTURED;

EID: 13344276592     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950619p     Document Type: Article

References (30)

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10. Haefliger, W.; Hauser, D. Isolierung und Strukturaufklärung von 11-Desacetoxy-wortmannin. (Isolation and structure elucidation of 11-deacetoxywortmannin.) Helv. Chim. Acta 1973, 56, 2901-2904. Haefliger, W.; Kis, Z.; Hauser, D. Selektive Funktionalisierung von Wortmannin mit Hilfe einer Furanring-Maskierung. (Selective functionalization of wortmannin using furan ring masking.) Helv. Chim. Acta 1975, 58, 1620-1628. Haefliger, W.; Hauser, D. Einführung der Corticoid-Seitenkette bie Wortmannin. (Introduction of the corticoid side chain into wortmannin.) Helv. Chim. Acta 1975, 58, 1629-1633.
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13. Our PI 3-kinase assay, which utilizes purified enzyme from bovine brain has been described in detail in ref 6.
14. 1H NMR and was observed for all of the primary amine adducts (3a-d). This effect has been previously addressed (see ref 9).
15. -5. It should be pointed out that wortmannin reacts with dimethylamine to give the product model 2, analogous to the reaction with diethylamine. We have chosen to use dimethylamine to simplify our thermodynamic calculations.
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