Discovery, synthesis and biological evaluation of a series of N-(phenylcarbamothioyl)-2-napthamides as inhibitors of Claudin-1

Viktoriya Mashinson, Thomas M. Webster, Anish K. Vadukoot, Kirsten T. Tolentino, Princess Simeon, Iram Fatima, Punita Dhawan, Corey R. Hopkins

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, despite advancements in diagnosis. The main reason for this is that many newly diagnosed CRC patients will suffer from metastasis to other organs. Thus, the development of new therapies is of critical importance. Claudin-1 protein is a component of tight junctions in epithelial cells, including those found in the lining of the colon. It plays a critical role in the formation and maintenance of tight junctions, which are essential for regulating the passage of molecules between cells. In CRC, claudin-1 is often overexpressed, leading to an increase in cell adhesion, which can contribute to the development and progression of the disease. Studies show that high levels of claudin-1 are associated with poor prognosis in CRC patients and targeting claudin-1 may have therapeutic potential for the treatment of CRC. Previously, we have identified a small molecule that inhibits claudin-1 dependent CRC progression. Reported herein are our lead optimization efforts around this scaffold to identify the key SAR components and the discovery of a key new compound that exhibits enhanced potency in SW620 cells.

Original languageEnglish (US)
Article number117416
JournalBioorganic and Medicinal Chemistry
Volume92
DOIs
StatePublished - Sep 7 2023

Keywords

  • Claudin-1
  • Colorectal cancer
  • In vitro PK
  • In vivo PK
  • Structure–activity relationship
  • Thiourea

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Discovery, synthesis and biological evaluation of a series of N-(phenylcarbamothioyl)-2-napthamides as inhibitors of Claudin-1'. Together they form a unique fingerprint.

Cite this