The specific role of O6-methylguanine-DNA methyltransferase inhibitors in cancer chemotherapy.

Abstract:

:The DNA repair protein, O6-methylguanine DNA methyltransferase (MGMT), can confer resistance to guanine O6-alkylating agents. Therefore, inhibition of resistant MGMT protein is a practical approach to increase the anticancer effects of such alkylating agents. Numerous small molecule inhibitors were synthesized and exhibited potential MGMT inhibitory activities. Although they were nontoxic alone, they also inhibited MGMT in normal tissues, thereby enhancing the side effects of chemotherapy. Therefore, strategies for tumor-specific MGMT inhibition have been proposed, including local drug delivery and tumor-activated prodrugs. Over-expression of MGMT in hematopoietic stem cells to protect bone marrow from the toxic effects of chemotherapy is also a feasible selection. The future prospects and challenges of MGMT inhibitors in cancer chemotherapy were also discussed.

journal_name

Future Med Chem

authors

Sun G,Zhao L,Zhong R,Peng Y

doi

10.4155/fmc-2018-0069

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

1971-1996

issue

16

eissn

1756-8919

issn

1756-8927

journal_volume

10

pub_type

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