Bisphosphonate-KBU2046 Conjugates for Bone-Targeted Cancer Therapy
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Solution Overview
Problem
There is a need for improved delivery and efficacy of oncology agents for treating cancers that metastasize to the bone, including breast, prostate, lung, kidney, thyroid, bladder, esophagus, stomach, liver, pancreas, testicles, skin, head and neck cancers, lymphomas, multiple myelomas, and sarcomas, as well as bone-related disorders such as osteoporosis, Paget's disease, and osteogenesis imperfecta.
Innovation Solution
Development of novel bisphosphonate-linked compounds, including those linking a bisphosphonate moiety with KBU2046, in the form of pharmaceutically acceptable salts, co-crystals, polymorphs, solvates, and enantiomers, which are administered to inhibit osteoclast-mediated bone degradation and treat bone-related cancers and disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional oncology agents are used to treat bone metastases, then cancer cells can be targeted, but delivery to bone tissue is insufficient and efficacy is limited
Solution Approach 1:
The patent combines an oncology agent (KBU2046) with a bisphosphonate moiety into a single conjugate molecule. The bisphosphonate component provides selective targeting to bone tissue through high affinity binding to hydroxyapatite, while the oncology agent provides cancer cell killing activity. This merging resolves the contradiction by ensuring both sufficient delivery to bone (via bisphosphonate targeting) and effective cancer treatment (via oncology agent activity).
Solution Approach 2:
The bisphosphonate moiety acts as an intermediary that mediates the delivery of the oncology agent to bone tissue. It serves as a targeting vector that carries the therapeutic payload specifically to the bone metastasis site, overcoming the limitation of poor delivery of conventional systemic administration.
2Adaptability or versatility
If multiple separate agents are used to treat bone metastases, then both cancer cells and bone degradation can be addressed, but treatment complexity increases
Solution Approach 1:
The patent merges multiple therapeutic functions into a single conjugate molecule. The bisphosphonate component addresses bone degradation through osteoclast inhibition, while the KBU2046 component addresses cancer cell proliferation and motility. This single agent performs what previously required multiple separate treatments, resolving the contradiction between treatment versatility and treatment complexity.
Solution Approach 2:
The conjugate molecule exhibits multi-functionality: it targets bone metastases, inhibits osteoclast-mediated bone degradation, and kills cancer cells. This universal agent replaces the need for multiple specialized treatments, simplifying the therapeutic regimen while maintaining comprehensive treatment capability.
Data Source
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AI summary
The present invention concerns novel compounds useful in the treatment of cancer, particularly including compounds linking a bisphosphonate moiety with KBU2046, and pharmaceutically acceptable salts, co-crystals, polymorphs, solvates, hydrates, and enantiomers thereof, as well as methods for their production and pharmaceutical compositions comprising them.