Nilotinib repositioning in cancers implying Cx43 tumorigenesis process

Abstract

Objective: Among the 21 human connexins, the ubiquitous protein Cx43 is the most abundant in many cell types. It is also associated with the tumorigenic process and the formation of metastases in several types of common cancers such as breast and colorectal cancers. Therefore, it constitutes an interesting therapeutic target in the fight against cancer. This study aims to search for drugs that could potentially interact with the Cx43 C-ter among the ones approved by the FDA. Materials and Methods: By molecular modeling, we selected four molecules among 1615 (Lumacaftor, Lomapitapide, Ponatinb and Nilotinib). We analyzed their interaction with Cx43 by molecular docking and molecular dynamics simulation Results: The analysis of data allowed to highlight Nilotinib as the molecule that can best target Cx43. Indeed, although the four molecules showed strong binding energies, probably due to the hydrophobic molecular interactions with the C-ter of Cx43, only Nilotinib remains stable during the 100 ns of simulation with 2-4 hydrogen bonds. Conclusions: All the molecules mentioned could play a non-negligible role in Cx43-mediated cancers. However, Nilotinib appears to be an optimal candidate in this context.

Keywords

• cx43
• cancer
• drug repurposing
• molecular docking
• md simulation