Neuropilin-1 and Neuropilin-2 (NRP1/NRP2)

Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2) are non-tyrosine kinase transmembrane glycoproteins that serve as critical co-receptors for various ligands, including the vascular endothelial growth factor (VEGF) family and class 3 semaphorins [UniProt, 2024]. NRP1 is primarily involved in VEGF-A-mediated angiogenesis and SEMA3A-mediated neuronal axon guidance, while NRP2 is essential for lymphangiogenesis and responds to VEGF-C and SEMA3F [PubMed: 22431812]. These receptors are frequently upregulated in multiple tumor types, where they facilitate tumor progression, epithelial-mesenchymal transition, and immune evasion by potentiating signaling through VEGFRs and Plexins [PubMed: 16166298]. In addition to their roles in cancer and development, NRP1 has been identified as a host entry factor for SARS-CoV-2, enhancing viral infectivity [PubMed: 32442134]. Therapeutic targeting of the neuropilin family involves monoclonal antibodies like Vesencumab and small molecule inhibitors designed to block the b1b2 ligand-binding domains [PubMed: 28651511]. Despite their potential, drug development is complicated by the receptors' widespread expression and their vital roles in vascular homeostasis and nervous system maintenance [PubMed: 23566695]. Current research also explores their role in fibrotic diseases and as potential targets for modulating the immune microenvironment in tumors [PubMed: 30104715].

Other names

NRPNPVEGF165RBDCA-4VEGF165R2

Neuropilin inhibitors typically function by binding to the extracellular b1b2 domains, thereby sterically hindering the interaction between neuropilins and their ligands, such as VEGF-A or Semaphorin 3A, which prevents the formation of active signaling complexes with VEGFRs or Plexins [PubMed: 22431812].