Discovering Negative Allosteric Modulators of Frizzled 4 Receptor Using the NPASS Database

Authors: Ni L
Publication: Saint Joseph’s University ProQuest Dissertations Publishing
Software: ADMET Predictor®


The class F G protein-coupled receptors (GPCRs) consists of the Smoothened receptor (SMO) and 10 Frizzled receptors (FZDs). Among the Frizzled receptors, FZD4 has been found to be upregulated in several cancers, highlighting its potential significance in tumorigenesis. To identify potential NAMs of FZD4, virtual screening techniques were employed using the X-ray crystallographic structure of FZD4 in its inactive state. Compounds from the NPASS database were screened, and five lead NAMs were selected based on their strong binding affinity and favourable ADMET profiles (absorption, distribution, metabolism, excretion, and toxicity). These lead drugs show promise for further development as selective and orally bioavailable NAMs of FZD4, providing potential new therapeutic options for targeting FZD4-associated signalling pathways in cancer. The development of small molecule orally bioavailable NAMs for FZD4 could offer an alternative approach for targeting FZD4-associated signalling pathways in cancer and potentially provide new therapeutic options.

By Ling Ni