NCI Drug Dictionary

The NCI Drug Dictionary contains technical definitions and synonyms for drugs/agents used to treat patients with cancer or conditions related to cancer. Each drug entry includes links to check for clinical trials listed in NCI's List of Cancer Clinical Trials.

LRP5/6 antagonist BI 905677
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. Check for active clinical trials using this agent. (NCI Thesaurus)

Synonym:anti-LRP5/6 nanobody BI 905677
Code name:BI 905677