Preferred Label : LRP5/6 Antagonist BI 905677;
NCIt synonyms : Anti-LRP5/6 Nanobody BI 905677;
NCIt definition : A humanized biparatopic nanobody composed of two blocking domains for the Wnt ligand
co-receptors lipoprotein receptor-related proteins (LRP) 5 and 6, with potential antineoplastic
and immunomodulating activities. Upon administration, BI 905677 targets and binds
to LRP5 and LRP6, thereby blocking the binding of Wnt ligands to LRP5/6. This prevents
the activation of the Frizzled (FZD)-Wnt-LRP5/6 trimeric complex and prevents the
inactivation of the beta-catenin degradation complex, which leads to beta-catenin
degradation. This inhibits the Wnt/beta-catenin signaling pathway, prevents the beta-catenin-mediated
activation of Wnt target genes, and inhibits the proliferation and survival of Wnt-driven
tumor cells. In addition, inhibition of Wnt signaling by BI 905677 prevents Wnt-mediated
immune escape, thereby re-activating the immune system, specifically inducing the
activation of dendritic cells (DCs) and activation as well as infiltration of cytotoxic
T-cells into the tumor tissue. The FZD-Wnt-LRP5/6 trimeric complex induces phosphorylation
of LRP5 or LRP6 intracellular domains leading to inactivation of the beta-catenin
degradation complex, allowing beta-catenin accumulation; stabilized beta-catenin enters
the nucleus and acts as a transcriptional activator of Wnt target genes. Wnt/beta-catenin
signaling plays a key role in tumorigenesis and resistance to immunotherapy.;
Molecule name : BI-905677; BI 905677;
NCI Metathesaurus CUI : CL978683;
Origin ID : C165553;
UMLS CUI : C5237262;
Semantic type(s)
- chemical_or_drug_has_physiologic_effect
- concept_is_in_subset
