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Novel Apelin Receptor Antagonist
Cancer Research Horizons
Peptide
Oncology
Hit To Lead or Lead Optimization
• Apelin is an endogenous peptide identified as a ligand of the G protein-coupled receptor APJ. Extensive tissue distribution of Apelin and its receptor suggests involvement in many physiological processes, and it has also been shown to participate in pathological processes such as heart failure and cancer. Apelin receptor is over-expressed in a number of cancers including glioblastoma (GBM), cervical, renal, lung and liver cancer.
• We have developed a lead compound, MM315, which is a potent competitive antagonist of the Apelin receptor, demonstrating a binding affinity of 2.4 nM (pA2=9.55 for cAMP). MM315 shows in vivo efficacy in GBM models, significantly extending survival in intracranial orthotopically implanted mice, and it has potential for synergy with temozolomide and radiation therapy.
