Altenusin

Altenusin is a polyphenol fungal metabolite originally isolated from the fungus Alternaria that has diverse biological activities.^1,2 It inhibits Src kinase with an IC₅₀ value of 20 nM.³ Altenusin inhibits fibrillization of recombinant tau fragments in vitro and phosphorylation of tau in SH-SY5Y cells expressing human P301L mutant tau when used at a concentration of 10 μM.¹ It is an agonist of the farnesoid X receptor (FXR; EC₅₀ = 3.2 μM) that reduces blood glucose, serum insulin, and serum cholesterol levels, as well as hepatic lipogenic gene expression and steatosis, in a high fat diet-induced mouse model of obesity when administered at 30 mg/kg per day.² Altenusin also has antioxidant and antifungal properties.

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1. Chua, S.W., Cornejo, A., van Eersel, J., et al. The polyphenol altenusin inhibits in vitro fibrillization of tau and reduces induced tau pathology in primary neurons. ACS Chem. Neurosci. 8(4), 743-751 (2017).

2. Zheng, Z., Zhao, Z., Li, S., et al. Altenusin, a nonsteroidal microbial metabolite, attenuates nonalcoholic fatty liver disease by activating the farnesoid X receptor. Mol. Pharmacol. 92(4), 425-436 (2017).

3. Oyama, M., Xu, Z., Lee, K.-H., et al. Fungal metabolites as potent protein kinase inhibitors: Identification of a novel metabolite and novel activities of known metabolites. Lett. Drug. Des. Discov. 100(1), 24-29 (2004).