University of Colorado

Colorado Research Partners. LLC

Miguel Lanaspa-Garcia

Richard J Johnson

William J Greenlee

Sundeep Dugar

Christopher J Rivard

MyPhuong Thi Le

Takuji Ishimoto

Gabriela Garcia

Disclosed herein are novel indazole-based compounds that inhibit fructokinase (aka ketohexokinase) and the downstream metabolic effects mediated by fructose metabolism. Fructokinase inhibitors specifically block the metabolism of both dietary and endogenous fructose metabolism and have a host of potential metabolic benefits. These benefits including blocking sugar craving and sugar induced metabolic syndrome and diabetes, but also blocking fructose metabolism can benefit the rare orphan disease Hereditary Fructose Intolerance, obesity, insulin resistance, metabolic syndrome, fatty liver, hypertension, cardiac injury from ischemia, certain cancers (including hepatocellular and pancreas), acute kidney injury from ischemia, heat stress, rhabdomyolysis or radiocontrast, and chronic diabetic and nondiabetic renal disease.

Indazole inhibitors of fructokinase (KHK) and methods of use in treating KHK-mediated disorders or diseases

The invention relates to the use of isoform-specific fructokinase (ketohexokinase) (KHK) inhibitors alone or in combination with various agents to both prevent and treat a wide variety of diseases including, but not limited to, sugar craving, obesity, features of metabolic syndrome (including insulin resistance, hypertriglyceridemia, hypertension, and fatty liver), polyuria, proximal tubular injury, and diabetic kidney disease.

Methods and compositions for the inhibition of fructokinase

The present invention provides compounds and compositions that modulate adenosine monophosphate deaminase (AMPD) and methods for using the same to treat a clinical condition associated with the metabolic syndrome or a disease associated with the metabolic syndrome. In particular, the present invention provides a compound and a composition comprising a selective AMPD2 inhibitor and methods for using the same, for example, to treat a clinical condition associated with metabolic syndrome as well as diseases manifested by the metabolic syndrome.

Methods of using AMPD2 inhibitors for the treatment of fatty liver, obesity and diabetes

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Denver, CO, United States of America

Miguel Lanaspa-Garcia