Design, synthesis of auristatins-glucuronide conjugates targeting the β-glucuronidase in tumor microenvironment

Auristatins-glucuronide conjugates designed targeting the beta-Glucuronidase in tumor microenvironment were synthesized and evaluated on stabilities, the release of auristatins and the antitumor activities in this study. Conjugates 20 and 21 showed remarkable stabilities in phosphate buffer and bovine serum solution, and excellent selectivity between the in vitro antiproliferative activities against beta-glucuronidase pretreated and untreated cancer cells (IC50 = 5.7 nM similar to 9.7 nM, IC50 (-Enz) > 1 NM). Furthermore, conjugate 20 showed potent antitumor efficacy in HCT-116 xenograft mouse model without inducing side effects.

Automated summary

Auristatins-glucuronide conjugates designed to target beta-Glucuronidase in the tumor microenvironment were synthesized and evaluated. The conjugates showed remarkable stability and selectivity in vitro antiproliferative activities against beta-glucuronidase pretreated and untreated cancer cells. Conjugate 20 exhibited potent antitumor efficacy in a mouse model without inducing side effects.