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

Andrew Beekman; Marco Cominetti; Oliver Cartwright; Dale L. Boger; Mark Searcey

doi:10.1039/C9MD00279K

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

Andrew Beekman, Marco Cominetti, Oliver Cartwright, Dale L. Boger, Mark Searcey

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Abstract

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.

Original language	English
Pages (from-to)	2170-2174
Number of pages	5
Journal	MedChemComm
Volume	10
Issue number	12
Early online date	27 Nov 2019
DOIs	https://doi.org/10.1039/C9MD00279K
Publication status	Published - Dec 2019

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10.1039/C9MD00279K

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Cite this

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abstract = "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.",

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AB - 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.

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