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

Yang Zhou, Saghar Mowlazadeh Haghighi, Zekun Liu, Lingzhi Wang, Victor J. Hruby, Minying Cai

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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 melanoma cell growth with an IC50 of 16 nM. By providing selectivity to melanoma cells through its MT-II moiety, this approach of drug-MT-II conjugates enables us to have many more options for cytotoxic drug selection, which can be the key to solving the cancer resistant problem for melanoma.

Original languageEnglish (US)
Pages (from-to)921-930
Number of pages10
JournalACS Pharmacology and Translational Science
Issue number5
StatePublished - Oct 9 2020


  • GPCR internalization
  • MC1R
  • ligand-drug conjugate
  • melanoma
  • targeted cancer therapy

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology


Dive into the research topics of 'Development of Ligand-Drug Conjugates Targeting Melanoma through the Overexpressed Melanocortin 1 Receptor'. Together they form a unique fingerprint.

Cite this