Development of Ligand-Drug Conjugates Targeting Melanoma through the Overexpressed Melanocortin 1 Receptor.

ABSTRACT: Melanoma is a lethal form of skin cancer. Despite recent breakthroughs of BRAF-V600E and PD-1 inhibitors showing remarkable clinical responses, melanoma can eventually survive these targeted therapies and become resistant. To solve the drug resistance issue, we designed and synthesized ligand-drug conjugates that couple cytotoxic drugs, which have a low cancer resistance issue, with the melanocortin 1 receptor (MC1R) agonist melanotan-II (MT-II), which provides specificity to MC1R-overexpressing melanoma. The drug-MT-II conjugates maintain strong binding interactions to MC1R and induce selective drug delivery to A375 melanoma cells through its MT-II moiety in vitro. Furthermore, using camptothecin as the cytotoxic drug, camptothecin-MT-II (compound 1) can effectively inhibit A375 me

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC7551717 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature