{"id":"01198","slug":"novel-small-molecule--01198","source":{"id":"01198","dataset":"techtransfer","title":"Novel Small Molecule Therapeutics for Hemorrhagic Shock","description_":"<p>Hemorrhagic shock and tissue hypoxia result in tissue conditions that are at risk of damage upon restored blood circulation. Subsequent oxygen reperfusion increases oxidative species concentrations even further, accelerating the decline of a patient’s systemic health. A patient undergoing severe blood loss suffers hypoxia during which lactic acid and other reactive oxidative species enter the circulatory system. These oxidative species are generated by “electron leakage” from the mitochondria and quickly spread throughout the circulatory system, oxidizing tissues and triggering cell death. Primary causes of hemorrhagic shock include penetrating and blunt trauma, gastrointestinal bleeding, and obstetrical bleeding. Controlling the activity of the reactive oxidative species is as crucial to patient survival as is controlling the bleeding.</p><p><h2>Description</h2>Investigators have developed a novel molecular delivery mechanism that allows hemorrhagic shock therapeutics to be targeted directly to the cell’s mitochondria. The lead compound, XJB-5-131, is a targeted nitroxide agent that allows delivery of the antioxidant TEMPO to the mitochondria using a peptide-like fragment of the antibiotic Gramicidin S. This localized concentration of TEMPO was found to provide greater therapeutic effects than those associated with standard TEMPO administration, providing test subjects with significantly longer survival times during prolonged hemorrhaging. This technology platform additionally allows for conjugation of the mitochondria targeting fragment of Gramicidin S to potentially any drug for delivery to the mitochondria for such indications.</p><p><h2>Applications</h2>· Treatment of any acute disease or condition that is associated with cellular damage or dysfunction caused by excessive mitochondrial production of reactive oxygen species, such as hemorrhagic shock, septic shock, or stroke</p><p><h2>Advantages</h2>· Intravenous treatment increases subject survival time during hemorrhagic shock, providing a greater window for treatment\r<br>· Preserves the protective mucosal lining of the intestines\r<br>· Antioxidant “payload” can be quickly directed to the mitochondria\r<br>· Lower conjugate drug concentrations can be administered\r<br>· Intravenous application delivers protection to the entire circulatory system’s endothelial lining</p><p><h2>Invention Readiness</h2>Proof of concept established\r\nMouse and rat data available</p><p><h2>IP Status</h2><a target=\"_blank\" href=\"https://patents.google.com/patent/US20070161573A1;\">https://patents.google.com/patent/US20070161573A1;</a> <a target=\"_blank\" href=\"https://patents.google.com/patent/US7718603B1;\">https://patents.google.com/patent/US7718603B1;</a> <a target=\"_blank\" href=\"https://patents.google.com/patent/US9006186B2;\">https://patents.google.com/patent/US9006186B2;</a> <a target=\"_blank\" href=\"https://patents.google.com/patent/US20150297578A1\">https://patents.google.com/patent/US20150297578A1</a></p><p><h2>Related Publication(s)</h2><p>Hoye, A. T., Davoren, J. E., Wipf, P., Fink, M. P., &amp; Kagan, V. E. (2008). Targeting Mitochondria. Accounts of Chemical Research, 41(1), 87–97. <a target=\"_blank\" href=\"https://doi.org/10.1021/ar700135m\">https://doi.org/10.1021/ar700135m</a></p></p>","tags":[],"file_number":"01198","collections":[{"key":517,"name":"Cardiometabolic"},{"key":555,"name":"Women's & Reproductive Health"}],"meta_description":"Mitochondria-targeted antioxidant therapy for hemorrhagic shock using XJB-5-131 delivers TEMPO directly, extending survival.","image_url":"","apriori_judge_output":"{\"scores\":{\"novelty\":4.0,\"potential_impact\":4.0,\"readiness\":2.0,\"scalability\":3.0,\"timeliness\":2.0},\"weighted_score\":3.25,\"risks\":[\"Age: date Jan 3, 2006; TRL 3 with initial in-vivo proof-of-concept may be outdated.\",\"Clinical translation risk for mitochondrial-targeted therapies.\",\"Potential safety concerns for mitochondrial targeting and off-target effects.\"],\"one_sentence_take\":\"Moderate novelty with strong potential impact but outdated readiness; promising platform but requires substantial validation for clinical translation.\"}","lead_inventor_name":"Peter Wipf","lead_inventor_dept":"Chemistry","technology_type":"Therapeutic Modality","technology_subtype":"Small Molecule","therapeutic_areas":["Endocrinology and Metabolic Diseases","Cardiovascular"],"therapeutic_indications":[],"custom_tags":[],"all_tech_innovators":["Mitchell Phillip Fink MD","Valerian E. Kagan PhD, DSc","Yulia Yurjevna Tyurina","Peter Wipf","Jingbo Xiao"],"date_submitted":"2006-01-03","technology_readiness_level":"3. Initial proof of concept, in-vivo"},"highlight":{},"matched_queries":null,"score":0.0}