Organotrifluoroborate mimics of amino acids and uses thereof
Patent Number: WO2016176572
Executive Summary:
General Description:
Boron mimics of amino acids are compounds created by substituting the carboxylate group (-COO-) of an amino acid with trifluoroborate (-BF3-). The boramino acids (or BAA) of the present invention are metabolically stable in vivo and non-distinguishable to natural amino acid transporters. Compared with traditional amino acid drugs, boramino acids provide better specificity and efficacy for cancer treatments. Indeed, highly replicating cancer cells overexpress amino acid transporters and, therefore, uptake higher concentration of BAAs compared to healthy tissue. Therefore, BAAs could be very efficacious in cancer treatments like the boron neutron capture therapy (BNCT). BCNT is a non-invasive treatment that utilizes a boron-containing capture agent and relies on the propensity of the boron to capture slow neutrons. After administration of the capture agent, the patient is irradiated with neutrons that penetrate the tissue and are absorbed by the boron of the capture agent. Upon absorption, the capture agent emits high-energy particles that destroy the cells containing the capture agent itself. As BAAs are concentrated in tumor tissue, the BAAs of the present invention represent potentially efficient capture agents to be employed in BCNT. Moreover, BAAs could be labeled with fluorene-18 (18F) and used as tracer for imaging tumors using positron emission tomography (PET). By imaging the tumor at different times, tumor size could be followed and used to evaluate the effectiveness of potential anti-cancer drugs.
Strengths:
Weaknesses:
Patent Status:
Publications:
Boramino acid as a marker for amino acid transporters. Liu Z, Chen H, Chen K, Shao Y, Kiesewetter DO, Niu G, Chen X. Sci Adv. 2015 Sep 11;1(8):e1500694. doi: 10.1126/sciadv.1500694. eCollection 2015 Sep. PMID: 26601275
Inventor Bio: Xiaoyuan Chen
https://www.nibib.nih.gov/about-nibib/staff/xiaoyuan-chen
Executive Summary:
- Invention Type: Diagnostic/Therapeutic
- Patent Status: International Application
- Patent Link: https://www.google.com/patents/WO2016176572
- Research Institute: NIH/NHLBI/NIBIB
- Disease Focus: Glioma, prostate cancer, and pancreas cancer; other cancers
- Basis of Invention: Generation of boron amino acids (BAA) by substituting the carboxylate group (-COO-) with trifluoroborate (-BF3-). Fluorene-18 labeling
- How it works: BAAs could be used as tracer for positron emission tomography (PET) imaging of cancers and neutron-capture agents employed in boron neutron capture therapy (BNCT)
- Lead Challenge Inventor: Xiaoyuan Chen
- Inventors: Zhibo Liu, Xiaoyuan Chen
- Development Stage: Pre-clinical (in vivo data available)
- Novelty:
- Traceable amino acid mimics for imaging and neuron capture therapy
- Clinical Applications:
- Imaging technology for clinical diagnosis and anti-cancer drug evaluation
- Cancer therapy
General Description:
Boron mimics of amino acids are compounds created by substituting the carboxylate group (-COO-) of an amino acid with trifluoroborate (-BF3-). The boramino acids (or BAA) of the present invention are metabolically stable in vivo and non-distinguishable to natural amino acid transporters. Compared with traditional amino acid drugs, boramino acids provide better specificity and efficacy for cancer treatments. Indeed, highly replicating cancer cells overexpress amino acid transporters and, therefore, uptake higher concentration of BAAs compared to healthy tissue. Therefore, BAAs could be very efficacious in cancer treatments like the boron neutron capture therapy (BNCT). BCNT is a non-invasive treatment that utilizes a boron-containing capture agent and relies on the propensity of the boron to capture slow neutrons. After administration of the capture agent, the patient is irradiated with neutrons that penetrate the tissue and are absorbed by the boron of the capture agent. Upon absorption, the capture agent emits high-energy particles that destroy the cells containing the capture agent itself. As BAAs are concentrated in tumor tissue, the BAAs of the present invention represent potentially efficient capture agents to be employed in BCNT. Moreover, BAAs could be labeled with fluorene-18 (18F) and used as tracer for imaging tumors using positron emission tomography (PET). By imaging the tumor at different times, tumor size could be followed and used to evaluate the effectiveness of potential anti-cancer drugs.
Strengths:
- Metabolic stability
- Fluorene-18 labeling
- Boron
Weaknesses:
- The findings of the present invention have not been independently reproduced by others
- The patent for the present invention has not been granted yet
Patent Status:
- Priority date: 2015-04-30
- Filing date: 2016-04-29
- Publication date: 2016-11-03
Publications:
Boramino acid as a marker for amino acid transporters. Liu Z, Chen H, Chen K, Shao Y, Kiesewetter DO, Niu G, Chen X. Sci Adv. 2015 Sep 11;1(8):e1500694. doi: 10.1126/sciadv.1500694. eCollection 2015 Sep. PMID: 26601275
Inventor Bio: Xiaoyuan Chen
https://www.nibib.nih.gov/about-nibib/staff/xiaoyuan-chen