Mechanisms of action of quinone-containing alkylating agents i: NQO1-directed drug development

10.2741/beall ◽  
2000 ◽  
Vol 5 (1) ◽  
pp. d639 ◽  
Author(s):  
Howard, D. Beall
2007 ◽  
Vol 54 (3) ◽  
pp. 459-468 ◽  
Author(s):  
Jadwiga Nieminuszczy ◽  
Elzbieta Grzesiuk

Environmental and endogenous alkylating agents generate cytotoxic and mutagenic lesions in DNA. Exposure of prokaryotic cells to sublethal doses of DNA alkylating agents induces so called adaptive response (Ada response) involving the expression of a set of genes which allows the cells to tolerate the toxic and mutagenic action of such agents. The Ada response includes the expression of four genes: ada, alkA, alkB, and aidB. The product of ada gene, Ada protein, is an activator of transcription of all four genes. DNA bases damaged by alkylation are removed by distinct strategies. The most toxic lesion 3meA is removed by specific DNA glycosylase initiating base excising repair. The toxic and mutagenic O6meG is repaired directly by methyltransferases. 1meA and 3meC are corrected by AlkB DNA dioxygenase. The mechanisms of action of E. coli AlkB dioxygenase and its human homologs ABH2 and ABH3 are described in more details.


2016 ◽  
pp. 186-195
Author(s):  
David Kerr ◽  
Daniel Haller ◽  
Jaap Verweij

This chapter discusses the principles of chemotherapy, and includes information on the mechanism of action of commonly available drugs (anthracyclines, Vinca alkaloids, taxenes, alkylating agents, bleomycin, platinum–based agents, antimetabolites, topoisomerase inhibitors, hormonal agents, antiandrogens, cell signalling inhibitors, and growth factor receptor inhibitors), cellular principles of chemotherapy, pharmacological principles of chemotherapy (effects of hepatic and renal impairment, pharmacogenetics, dose intensity, locoregional drug administration, increase of the dose per administration, and treatment intervals), principles of combination chemotherapy (activity as a single agent, different mechanisms of action and resistance, dose-limiting toxicities, and cell-cycle-related and biochemical interactions), and adjuvant and neoadjuvant systemic therapy.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Angela Jiang ◽  
Jillian Wang ◽  
Malav Joshi ◽  
John Byron Christoforidis

Vitreous inflammation, or vitritis, may result from many causes, including both infectious and noninfectious, including rheumatologic and autoimmune processes. Vitritis is commonly vision threatening and has serious sequelae. Treatment is frequently challenging, but, today, there are multiple methods of systemic treatment for vitritis. These categories include corticosteroids, antimetabolites, alkylating agents, T-cell inhibitors/calcineurin inhibitors, and biologic agents. These treatment categories were reviewed last year, but, even over the course of just a year, many therapies have made progress, as we have learned more about their indications and efficacy. We discuss here discoveries made over the past year on both existing and new drugs, as well as reviewing mechanisms of action, clinical dosages, specific conditions that are treated, adverse effects, and usual course of treatment for each class of therapy.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
John B. Christoforidis ◽  
Susie Chang ◽  
Angela Jiang ◽  
Jillian Wang ◽  
Colleen M. Cebulla

Non infectious vitreous inflammation is often vision threatening and can be associated with potentially life-threatening systemic conditions. Treatment is often challenging as it involves systemic medications that can be associated with adverse effects. The classes of drugs are ever expanding and include corticosteroids, antimetabolites, alkylating agents, T-cell and calcineurin agents, biologic agents, and interferons. Each class of systemic therapy for non-infectious vitreous inflammation is reviewed. We discuss the mechanisms of action, usual clinical dosages, the specific conditions that are treated, the adverse effects, and usual course of treatment for each class of therapy.


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