Nov. 3, 2015
Small molecule fatty acid uptake inhibitors as potential treatment for obesity and other metabolic disorders.
University of Nebraska—Lincoln researchers, Drs. Concetta DiRusso & Paul Black, used a proprietary high-throughput screening method to identify and characterize in cell based assays compounds that inhibit FATP2 mediated fatty acid uptake. The compounds have unique structural properties, are not toxic to cells, do not disrupt the cell-cell contacts required for barrier function, and are specific to long chain fatty acid transport. These compounds have potential therapeutic applicability for the prevention and resolution of diseases involving fatty acid uptake and metabolism including but not limited to obesity, Type 2 Diabetes, metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease.
• Proprietary screen to identify small molecule inhibitors of FATP2 mediated fatty acid uptake
• Compound efficacy and safety have been confirmedin vivo&in vitro
• Effective at micro-molar concentrationsin vitro
Ahowesso, C., Black, P. N., Saini, N., Montefusco, D., Chekal, J., Malosh, C., Lindsley, C. W., Stauffer, S. R., and DiRusso, C. C. (2015) Chemical inhibition of fatty acid absorption and cellular uptake limits lipotoxic cell death .Biochem Pharmacol
Saini, N., Black, P. N., Montefusco, D., and DiRusso, C. C. (2015) Fatty acid transport protein-2 inhibitor Grassofermata/CB5 protects cells against lipid accumulation and toxicity .Biochem Biophys Res Commun465, 534-541
Sandoval, A., Chokshi, A., Jesch, E. D., Black, P. N., and Dirusso, C. C. (2010) Identification and characterization of small compound inhibitors of human FATP2 .Biochem Pharmacol79, 990-999
Li, H., Black, P. N., Chokshi, A., Sandoval-Alvarez, A., Vatsyayan, R., Sealls, W., and DiRusso, C. C. (2008) High-throughput screening for fatty acid uptake inhibitors in humanized yeast identifies atypical antipsychotic drugs that cause dyslipidemias .J Lipid Res49, 230-244
NUtech Ventures is the non-profit technology commercialization affiliate of the University of Nebraska—Lincoln. Our mission is to facilitate the commercialization and practical use of innovations generated through the research activities at the University of Nebraska.
Treatment for obesity and other metabolic disorders
• Low toxicity
• Fatty acid uptake inhibition is specific to long chain fatty acid transport
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unique structural properties
cell-cell contacts required
• proprietary screen
vitro • effective
fatty acid absorption
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