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Novel small molecules for treating NASH

Novel candidates for NASH: Novel thiourea derivatives bind to RORα protein which leads to suppression of lipid accumulation in hepatocytes

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Place of Origin: South Korea

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Keyword: nash, metabolic disease, small molecule, rorα activator

Category: Medicines

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Seoul National University R&DB Foundation

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Country / Year Established: South Korea / 2003

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Unmet Needs

• Nonalcoholic steatohepatitis (NASH) is a liver disease that is characterized by the accumulation of fat in the liver, inflammation, and liver cell damage with multiple underlying factors contributing to its pathogenesis such as obesity, insulin resistance, dyslipidemia, and gut dysbiosis

• There are currently no FDA-approved drugs for the treatment of NASH, and clinical management involves lifestyle modifications such as weight loss, dietary changes, and exercise

Technology Overview

• Exacerbation of non-alcoholic steatohepatitis (NASH) is associated with mitochondrial dysfunction and a homeostatic imbalance

• Retinoic acid receptor-related orphan receptor α (RORα) enhances oxygen consumption rate and expression of genes associated with mitochondrial quality control

• Novel thiourea derivatives directly bind to RORα protein and increase transcriptional activity which leads to suppression of lipid accumulation in hepatocytes

Patent Pending

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PCT

PCT-KR2022-017924

2022.11.15

Unpublished

Paper

Lee, Mi-Ock, et al. “RORα suppresses interleukin-6-mediated hepatic acute phase response”. Sci Rep. 2019 Aug 13;9(1):11798.

Park, Hyeung-Geun, et al. “Enantioselective Synthesis of Chiral α‐Alkylthiomalonates via a Phase‐Transfer‐Catalyzed α‐Sulfenylation of α‐Alkylmalonates”. Asian J. Org. Chem. 2019, 8, 1732–1739.