A small molecule drug conjugate (SMDC) of DUPA and a duocarmycin built on the solid phase.

In a proof-of-concept study, solid phase synthesis allowed the rapid generation of a small molecule drug conjugate in which the glutamate carboxypeptidase II (GCPII) targeting small molecule DUPA was conjugated to the alkylating subunit of the potent cytotoxin duocarmycin SA. The targeted SMDC contained a cathepsin B cleavable linker, which was shown to be active and selective against cathepsin B over-expressing and GCPII-expressing tumour cell lines.