Novel analogues of CC-1065 and the duocarmycins for the use in targeted tumour therapies
- PMID: 19275523
- DOI: 10.2174/1871520610909030304
Novel analogues of CC-1065 and the duocarmycins for the use in targeted tumour therapies
Abstract
In recent years, a series of new and highly cytotoxic analogues of CC-1065 and the duocarmycins have been developed that can be transformed into much less toxic prodrugs for the use in antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) and prodrug monotherapy (PMT) of cancer. In all these approaches, a relatively non-toxic prodrug is applied and subsequently converted selectively in the tumour tissue into a highly cytotoxic drug, thus reducing undesired side effects accompanying conventional chemotherapy. Here, the design and biological evaluation of prodrugs based on analogues of CC-1065 and the duocarmycins for the use in tumour selective cancer therapies is reviewed. The advantage of this approach is the excellent therapeutic index of some of the new prodrugs of over 5000 and the high cytotoxicity of the corresponding drugs with IC(50) values of as low as 16 pM (IC(50): concentration required for 50 % growth inhibition of target cells). In addition, a novel method for the correlation of the alkylation efficiency and the cytotoxicity based on mass spectrometry is described.
Similar articles
-
Selective treatment of cancer: synthesis, biological evaluation and structural elucidation of novel analogues of the antibiotic CC-1065 and the duocarmycins.Chemistry. 2007;13(16):4396-409. doi: 10.1002/chem.200700113. Chemistry. 2007. PMID: 17455190
-
Prodrugs for targeted tumor therapies: recent developments in ADEPT, GDEPT and PMT.Curr Pharm Des. 2011;17(32):3527-47. doi: 10.2174/138161211798194459. Curr Pharm Des. 2011. PMID: 22074425 Review.
-
Asymmetric synthesis and biological evaluation of glycosidic prodrugs for a selective cancer therapy.ChemMedChem. 2008 Dec;3(12):1946-55. doi: 10.1002/cmdc.200800250. ChemMedChem. 2008. PMID: 19021160
-
Antibody-directed enzyme prodrug therapy: a promising approach for a selective treatment of cancer based on prodrugs and monoclonal antibodies.Chem Biol Drug Des. 2009 Sep;74(3):205-11. doi: 10.1111/j.1747-0285.2009.00856.x. Epub 2009 Jul 29. Chem Biol Drug Des. 2009. PMID: 19660031
-
Beta-glucuronidase-mediated drug release.Curr Pharm Des. 2002;8(15):1391-403. doi: 10.2174/1381612023394485. Curr Pharm Des. 2002. PMID: 12052215 Review.
Cited by
-
Determination of the biological activity and structure activity relationships of drugs based on the highly cytotoxic duocarmycins and CC-1065.Toxins (Basel). 2009 Dec;1(2):134-50. doi: 10.3390/toxins1020134. Epub 2009 Dec 2. Toxins (Basel). 2009. PMID: 22069536 Free PMC article.
-
Evaluation of a reductively activated duocarmycin prodrug against murine and human solid cancers.Cancer Biol Ther. 2013 Jun;14(6):527-36. doi: 10.4161/cbt.24348. Cancer Biol Ther. 2013. PMID: 23760495 Free PMC article.
-
Asymmetric synthesis of a CBI-based cyclic N-acyl O-amino phenol duocarmycin prodrug.J Org Chem. 2014 Oct 17;79(20):9699-703. doi: 10.1021/jo501839x. Epub 2014 Oct 3. J Org Chem. 2014. PMID: 25247380 Free PMC article.
-
Diversity of the reaction mechanisms of SAM-dependent enzymes.Acta Pharm Sin B. 2021 Mar;11(3):632-650. doi: 10.1016/j.apsb.2020.08.011. Epub 2020 Aug 26. Acta Pharm Sin B. 2021. PMID: 33777672 Free PMC article. Review.
-
A radical S-adenosyl-L-methionine enzyme and a methyltransferase catalyze cyclopropane formation in natural product biosynthesis.Nat Commun. 2018 Jul 17;9(1):2771. doi: 10.1038/s41467-018-05217-1. Nat Commun. 2018. PMID: 30018376 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
