Neuropilin (NRPs) Related Pathological Conditions and Their Modulators

Abstract

Neuropilin 1 (NRP1) represents one of the two homologous neuropilins (NRP, splice variants of neuropilin 2 are the other) found in all vertebrates. It forms a transmembrane glycoprotein distributed in many human body tissues as a (co)receptor for a variety of different ligands. In addition to its physiological role, it is also associated with various pathological conditions. Recently, NRP1 has been discovered as a coreceptor for the SARS-CoV-2 viral entry, along with ACE2, and has thus become one of the COVID-19 research foci. However, in addition to COVID-19, the current review also summarises its other pathological roles and its involvement in clinical diseases like cancer and neuropathic pain. We also discuss the diversity of native NRP ligands and perform a joint analysis. Last but not least, we review the therapeutic roles of NRP1 and introduce a series of NRP1 modulators, which are typical peptidomimetics or other small molecule antagonists, to provide the medicinal chemistry community with a state-of-the-art overview of neuropilin modulator design and NRP1 druggability assessment.

NRP1 promotes prostate cancer progression via modulating EGFR-dependent AKT pathway activation

“…5E, F ). A previous study reported that NRP1 can act as a co-receptor of multiple tyrosine kinase receptors to promote tumor proliferation and migration [ 27 ]. Thus, it can be speculated that NRP1 may interact with EGFR and modulate EGFR phosphorylation.…”

Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications

“…They act as co-receptors for proteins such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and transforming growth factor β (TGF-β). 7,9 There are two NRPs (NRP1 and NRP2) encoded by different genes on independent chromosomes but with a common domain structure. 8,9 While both NRPs share some characteristics and ligands, they differ in their tissue distribution and modulated signaling pathways.…”

“…7,9 There are two NRPs (NRP1 and NRP2) encoded by different genes on independent chromosomes but with a common domain structure. 8,9 While both NRPs share some characteristics and ligands, they differ in their tissue distribution and modulated signaling pathways. 8,10 Moreover, while NRP1 has been widely studied and characterized, fewer studies have focused on NRP2.…”

“…8,10 Moreover, while NRP1 has been widely studied and characterized, fewer studies have focused on NRP2. 9 Nevertheless, the role played by both NRPs in cancer, including HCC, has recently become of interest due to their strong correlation with key cellular and molecular mechanisms involved in tumor progression. 8,9 Interestingly, despite increasing studies evaluating the role of NRP1 and NRP2 in human HCC, no attempt has been made to compile the main findings of their potential roles in the HCC tumor landscape.…”

“…9 Nevertheless, the role played by both NRPs in cancer, including HCC, has recently become of interest due to their strong correlation with key cellular and molecular mechanisms involved in tumor progression. 8,9 Interestingly, despite increasing studies evaluating the role of NRP1 and NRP2 in human HCC, no attempt has been made to compile the main findings of their potential roles in the HCC tumor landscape. Therefore, we aimed to summarize through a systematic literature review the findings of published studies using preclinical and/or clinical HCC models and evaluating one or both NRPs.…”