{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cui J"],"funding":["Wntrix INC","Janice David Gordon Endowment for Bowel Cancer Research","National Cancer Institute","NCI NIH HHS","Cancer Prevention and Research Institute of Texas"],"pagination":["12572-12581"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8713425"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["64(17)"],"pubmed_abstract":["LGR4-6 (leucine-rich repeat-containing G-protein-coupled receptors 4, 5, and 6) are three related receptors with an upregulated expression in gastrointestinal cancers to various extents, and LGR5 is enriched in cancer stem cells. Antibody-drug conjugates (ADCs) targeting LGR5 showed a robust antitumor effect in vivo but could not eradicate tumors due to plasticity of LGR5-positive cancer cells. As LGR5-negative cancer cells often express LGR4 or LGR6 or both, we reasoned that simultaneous targeting of all three LGRs may provide a more effective approach. R-spondins (RSPOs) bind to LGR4-6 with high affinity and potentiate Wnt signaling. We identified an RSPO4 furin domain mutant (Q65R) that retains potent LGR binding but no longer potentiates Wnt signaling. Drug conjugates of a peptibody co"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Drug Conjugates of Antagonistic R-Spondin 4 Mutant for Simultaneous Targeting of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors 4/5/6 for Cancer Treatment."],"pmcid":["PMC8713425"],"funding_grant_id":["R01CA226894","RP190542","R01 CA226894"],"pubmed_authors":["Carmon KS","Wu L","Jacob J","Toh Y","Pan S","Cui J","Yu W","Tu J","Liu QJ","Park S","Li L"],"additional_accession":[]},"is_claimable":false,"name":"Drug Conjugates of Antagonistic R-Spondin 4 Mutant for Simultaneous Targeting of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors 4/5/6 for Cancer Treatment.","description":"LGR4-6 (leucine-rich repeat-containing G-protein-coupled receptors 4, 5, and 6) are three related receptors with an upregulated expression in gastrointestinal cancers to various extents, and LGR5 is enriched in cancer stem cells. Antibody-drug conjugates (ADCs) targeting LGR5 showed a robust antitumor effect in vivo but could not eradicate tumors due to plasticity of LGR5-positive cancer cells. As LGR5-negative cancer cells often express LGR4 or LGR6 or both, we reasoned that simultaneous targeting of all three LGRs may provide a more effective approach. R-spondins (RSPOs) bind to LGR4-6 with high affinity and potentiate Wnt signaling. We identified an RSPO4 furin domain mutant (Q65R) that retains potent LGR binding but no longer potentiates Wnt signaling. Drug conjugates of a peptibody co","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2026-05-09T16:15:12.503Z","creation":"2024-12-03T16:10:10.889Z"},"accession":"S-EPMC8713425","cross_references":{"pubmed":["34406767"],"doi":["10.1021/acs.jmedchem.1c00395"]}}