Nedaplatin

As a platinum analog, nedaplatin likely works similarly to DB00515 on which the following mechanistic description is based. Once it has entered the cell it is hydrolyzed to its active form which complexes with water molecules. This form binds to to nucleophiles in the cytoplasm such as glutathione and other cyteine rich proteins resulting in an overall increase in oxidative stress as the cell loses antioxidant proteins. It also binds to purine nucleotides in the DNA. The active form allows for two binding interactions to form cross-links between these nucleotides. High mobility group proteins-1 and -2 induce apoptosis in response to guanine cross-links and their binding serves to shield the cross-linked DNA from repair mechanisms. The mismatch repair (MMR) protein complex also recognizes the distortion caused by platinum complexes and attempts to repair the DNA. This results in single strand breaks when the MMR complex attempts to remove the platinum cross-link. The MMR complex induces apoptosis after the repair attempt has failed. The single strand break in DNA makes it easier to form lethal double strand breaks with radiation treatment thus creating the radiosensitizing effect of nedaplatin.