Increasing the Potential of the Auristatin Cancer-Drug Family by Shifting the Conformational Equilibrium.

ABSTRACT: Monomethyl auristatin E and monomethyl auristatin F are widely used cytotoxic agents in antibody-drug conjugates (ADCs), a group of promising cancer drugs. The ADCs specifically target cancer cells, releasing the auristatins inside, which results in the prevention of mitosis. The auristatins suffer from a potentially serious flaw, however. In solution, the molecules exist in an equal mixture of two conformers, cis and trans. Only the trans-isomer is biologically active and the isomerization process, i.e., the conversion of cis to trans is slow. This significantly diminishes the efficiency of the drugs and their corresponding ADCs, and perhaps more importantly, raises concerns over drug safety. The potency of the auristatins would be enhanced by decreasing the amount of the biologically ina

SUBMITTER: Sokka IK 

PROVIDER: S-EPMC6750905 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature