[Five classes of anticarcinogens--phorbol ester antagonists].
Literary data concerning structure-activity relationships in compounds exhibiting an antipromoter activity in skin tests of full tumour promotion by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or its analogs have been reviewed. Five classes of antipromoters differing in their action on the first and second stages of tumour promotion have been identified, namely: i) 2nd stage promoters/1st stage inhibitors; ii) 1st stage promoters/2nd stage inhibitors; iii) 2nd stage inhibitors; iiii) 1st stage inhibitors; iiiii) 1st and 2nd stage inhibitors. The results on structure-activity of antipromoters were compared with the results of previous studies on phorbol tumour promoters. These data made it possible to determine the reciprocal localization of binding sites for various classes of antipromoters and individual functionally important phorbol fragments on protein kinase C. A new detailed variant of the model of two-center binding of full phorbol tumour promoters on protein kinase C is proposed.
Kozhemiakina
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Iaguzhinskiĭ
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D003043:Cocarcinogenesis; D004336:Drug Antagonism; D010703:Phorbol Esters / Q000633:toxicity*; D011493:Protein Kinase C / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D016588:Anticarcinogenic Agents; D010703:Phorbol Esters; D011493:Protein Kinase C