Impaired migration and lung invasion of human melanoma by a novel small molecule targeting the ...

ABSTRACT: Receptor transmembrane domains (TMDs) are crucially involved in relaying ligand information from extracellular to intracellular spaces and represent attractive targets for small molecule manipulation of receptor function. Screening a library of over 8,000 drug-like compounds with an assay based on the TMD of death receptor p75NTR, we identified a novel small molecule capable of inhibiting p75NTR-mediated migration of human melanoma cells. Employing medicinal chemistry, a more potent derivative termed Np75-4A22 was identified that blocked nerve growth factor (NGF)-mediated melanoma invasion at sub-micromolar concentrations. The specific interaction of Np75-4A22 with the p75NTR TMD was confirmed by 2D NMR. Mechanistically, Np75-4A22 was found to antagonize NGF-mediated recruitment of the act

SUBMITTER: Vanessa Lopes-Rodrigues 

PROVIDER: S-SCDT-10_1038-S44321-025-00297-1 | biostudies-other |

REPOSITORIES: biostudies-other