Bifunctional antagonists of activator proteins/TGF-beta and RANKL and uses thereof

• Main Authors: HAN HUIQUAN, ZHOU XIAOLAN
• Format: Patent
• Language: Chinese; English
• Published: 20.10.2023
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present disclosure provides novel bifunctional molecules comprising at least one RANKL binding molecule and at least one activator protein or TGF-beta binding molecule capable of concurrently isolating RANKL and activator protein or TGF-beta. Also provided are pharmaceutical compositions of such bifunctional antagonist molecules and their therapeutic use for the treatment of various bone disorders, the pathogenesis of which involves both activation of RANKL-NF [kappa] B and activation of the protein/TGF [beta]-Smad2/3 signaling pathway, the bone disorders such as bone metastasis, bone loss in cancer, bone brittleness in neuromuscular disease, osteogenesis imperfection, fracture, osteopenia, and osteoporosis. 本发明公开内容提供了新颖的双功能分子，其包含至少一种RANKL结合分子和至少一种激活蛋白或TGF-β结合分子，其能够并行地隔离RANKL和激活蛋白或TGF-β。还提供了这样的双功能拮抗剂分子的药物组合物及其用于治疗各种骨紊乱的治疗用途，这些骨紊乱的发病机制涉及激活RANKL-NFκB和激活蛋白/TGFβ-Smad2/3信号传导途径两者，所述骨紊乱诸如骨转移、癌症中的骨损失、神经肌肉疾病中的骨脆性、成骨不全、骨折、骨质减少和骨质疏松。