SKI606 Src Kinase Inhibitor Osteolytic Lesion Treatment
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Solution Overview
Problem
Current treatments for bone metastases associated with cancer, such as bisphosphonate therapy, only delay skeletal events and do not completely prevent them, and not all patients respond to this treatment, highlighting the need for a more effective biological and molecular approach to regulate osteoclastogenesis and prevent bone destruction.
Innovation Solution
The use of specific compounds, including 4-((2,4-Dichloro-5-methoxyphenyl) amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl) propoxy)-3-quinolinecarbonitrile, and its pharmaceutically acceptable salts, which inhibit osteoclastogenesis and bone resorption by targeting the RANK signal transduction machinery, thereby preventing unwanted bone destruction associated with cancer and metabolic bone disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bisphosphonate therapy is used to treat bone metastases, then skeletal events are delayed, but they are not completely prevented and not all patients respond
Solution Approach 1:
The patent changes the therapeutic parameter from bisphosphonates (which inhibit osteoclast function) to RANKL inhibitors (which prevent osteoclast formation). This parameter change targets the upstream RANK signaling pathway, providing a more effective and reliable treatment that addresses the root cause of osteoclast-mediated bone destruction in metastatic cancer patients.
Solution Approach 2:
The patent extracts and targets the specific RANKL-RANK interaction pathway from the complex bone remodeling system. By using monoclonal antibodies or soluble receptors that specifically bind RANKL, the invention isolates and inhibits this critical signaling step, preventing osteoclastogenesis without affecting other bone metabolic processes.
2Object-affected harmful factors
If RANKL-RANK interaction is inhibited to prevent osteoclastogenesis, then bone destruction is reduced, but complete elimination of osteoclast activity may cause osteopetrosis
Solution Approach 1:
The patent applies partial inhibition of the RANKL-RANK interaction rather than complete blockade. By using soluble decoy receptors or monoclonal antibodies at controlled levels, the treatment partially reduces osteoclast formation and activity, sufficient to prevent metastasis-induced bone destruction while maintaining enough osteoclast function for normal bone remodeling and preventing osteopetrosis.
Data Source
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AI summary
The present invention include methods and compositions for treating bone-resorbing diseases or bone resorption related to a pathologic condition generally, including, but not limited to osteoporosis, arthritis, rheumatoid arthritis, cancer metastases to the bone, bone cancer, hypercalcemia, osteolytic lesions with orthopedic implants, Paget's disease, and bone loss associated with hyperparathyroidism. Representative cancers include, but are not limited to breast cancer, prostrate cancer, colon cancer, endometrial cancer, multiple myeloma, renal cell carcinoma, heck and neck cancers, and cervical carcinoma. Arthritic conditions include, but are not limited to adjuvant-, collagen-, bacterial- and antigen-induced arthritis, particularly rheumatoid arthritis.