Gregory J. Tesz

TL;DR: It is proposed that the small intestine shields the liver from otherwise toxic fructose exposure, finding that dietary fructose is cleared by theSmall intestine, both by prior exposure to fructose and by feeding.

TL;DR: It is demonstrated that sebum production in humans depends on local flux through the de novo lipogenesis (DNL) pathway within the sebocyte, highlighting the importance of local sebocytes DNL for human skin sebaceous gland biology and illuminating a potentially exploitable therapeutic target for the treatment of acne vulgaris.

TL;DR: The discovery of 12 is reported, a selective KHK inhibitor with potency and properties suitable for evaluating KHK inhibition in rat models, and key structural features interacting with KHK were discovered through fragment-based screening and subsequent optimization using structure-based drug design, and parallel medicinal chemistry led to the identification of pyridine 12.

TL;DR: In this paper, a small molecule inhibitor of the primary fructose metabolizing enzyme ketohexokinase (KHK) was used to block fructose metabolism in primary hepatocytes and Sprague Dawley rats fed either a high-fructose diet (30% fructose kcal/g) or a diet reflecting the average macronutrient dietary content of an American diet (AD).

TL;DR: The discovery of a first-in-class KHK inhibitor is reported, currently in phase 2 clinical trials, and the recognition of an alternative, rotated binding mode upon changing the ribose-pocket binding moiety from a pyrrolidinyl to an azetidinyl ring system enables efficient exploration of the vector directed at the Arg-108 residue.