title: From old alkylating agents to new minor groove binders.
abstract: Alkylating agents represent the oldest class of anticancer agents with the approval of mechloretamine by the FDA in 1949. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in the treatment of specific malignancies, sometimes representing the unique option for the treatment of refractory tumors. Here, we are reviewing the major classes of alkylating agents, with a particular focus on the latest generations of compounds that specifically target the minor groove of the DNA. These naturally occurring derivatives have a unique mechanism of action that explains the recent regain of interest in developing new classes of alkylating agents that could be used in combination with other anticancer drugs to enhance tumor response in the clinic.
authors: INSERM U916, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux cedex, France.
authors: Stéphane
authors: S
authors: Puyo
authors: INSERM U916, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux cedex, France.
authors: Danièle
authors: D
authors: Montaudon
authors: INSERM U916, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux cedex, France. Electronic address: philippe.pourquier@inserm.fr.
authors: Philippe
authors: P
authors: Pourquier
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D000478:Alkylation; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000477:Alkylating Agents; D018906:Antineoplastic Agents, Alkylating; D004247:DNA
keywords: Alkylating agents; DNA adducts; DNA crosslinks; DNA repair; O6-methylguanine