Development of novel alkylating drugs as anticancer agents.
Although conventional alkylating drugs have proven efficacy in the treatment of malignancies, the agents themselves are not selective. Therefore, non-specific alkylation of cellular nucleophilic targets may contribute to many of the observed toxic effects. Novel approaches to drug discovery have resulted in candidate agents that are focused on 'soft alkylation'--alkylators with greater target selectivity. This review highlights the discovery of small molecule drugs that bind to DNA with higher selectivity, act in a unique hypoxic tumor environment, or covalently bind specific protein targets overexpressed in cancer, such as topoisomerase II, glutathione transferase pi1, beta-tubulin and histone deacetylase.
Izbicka
Elzbieta
E
Cancer Therapy and Research Center, The Institute for Drug Development, 14960 Omicron Drive, San Antonio, TX 78245, USA. eizbicka@idd.org
Tolcher
Anthony W
AW
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D018906:Antineoplastic Agents, Alkylating; D015507:Drugs, Investigational