107474-63-5Relevant articles and documents
CHEMICAL LINKERS AND CLEAVABLE SUBSTRATES AND CONJUGATES THEREOF
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Page/Page column 73, (2010/06/19)
The present disclosure provides drug-ligand conjugates and drug-cleavable substrate conjugates that are potent cytotoxins. The disclosure is also directed to compositions containing the drug-ligand conjugates, and to methods of treatment using them.
Systematic exploration of the structural features of yatakemycin impacting DNA alkylation and biological activity
Tichenor, Mark S.,MacMillan, Karen S.,Trzupek, John D.,Rayl, Thomas J.,Hwang, Inkyu,Boger, Dale L.
, p. 10858 - 10869 (2008/03/13)
A systematic examination of the impact of the yatakemycin left and right subunits and their substituents is detailed along with a study of its unique three subunit arrangement (sandwiched vs extended and reversed analogues). The examination of the ca. 50 analogues prepared illustrate that within the yatakemycin three subunit structure, the subunit substituents are relatively unimportant and that it is the unique sandwiched arrangement that substantially increases the rate and optimizes the efficiency of its DNA alkylation reaction. This potentiates the cytotoxic activity of yatakemycin and its analogues overcoming limitations typically observed with more traditional compounds in the series (CC-1065, duocarmycins). Moreover, a study of the placement of the alkylation subunit within the three subunit arrangement (sandwiched vs extended and reversed analogues) indicates that it not only has a profound impact on the rate and efficiency of DNA alkylation but also controls and establishes the DNA alkylation selectivity as well, where both enantiomers of such sandwiched agents alkylate the same adenine sites exhibiting the same DNA alkylation selectivity independent of their absolute configuration.
