Baylor College of Medicine

Research Development Foundation

Other

Salih J Wakil

Lutfi Abu-Elheiga

Motonari Uesugi

Mizuki Watanabe

Akira Kugimiya

Qian Mao

Shinji Kamisuki

Martin Matthew Matzuk

The present invention relates to methods of treating a disease related to cell hyper-proliferation via administration of a therapeutically effective amount of a compound having a general tripartite structure A-B-C. In the tripartite structure A, B, and C are identical or non-identical structures, for example, but not limited to, heterocyclic, phenyl or benzyl ring structures with or without substitutions and are described in detail herein. The methods may utilize particular compounds, for example, having a piperidinyl, a pyrrolinyl or pyridinyl A ring, a thiazole B ring, and a phenyl C ring which may be further substituted independently.

Methods and compositions for the treatment of cancer and related hyperproliferative disorders

The present invention relates to methods for reducing body weight in an animal in need thereof via administration of a therapeutically effective amount of a compound having a general tripartite structure A-B-C. In the tripartite structure A, B, and C are identical or non-identical structures, for example, but not limited to, heterocyclic, phenyl or benzyl ring structures with or without substitutions and are described in detail herein. The methods may utilize particular compounds, for example, having a piperidinyl, a pyrrolinyl or pyridinyl A ring, a thiazole B ring, and a phenyl C ring which may be further substituted independently. Also provided are methods for increasing thermogenesis without reducing lean body mass during weight loss in an animal by administering of a therapeutically effective amount of the compounds described.

Methods and compositions for the treatment of body weight related disorders

The present invention relates to the compound for treatment and/or prevention of one or more metabolic disorders utilizes an A-B-C tripartite structure, wherein A, B, and C are identical or non-identical structures, for example, but not limited to, heterocyclic, phenyl or benzyl ring structures with or without substitutions and are described in detail herein. Also provided are methods for the treatment and/or prevention of one or more metabolic disorders, for example, obesity or diabetes, utilizing fatostatin A and/or a derivative and/or analog thereof and/or the A-B-C tripartite compounds.

Compositions and methods for the treatment of metabolic disorders

Compositions and methods for the treatment of metabolic and related disorders

The present invention relates to treatment and/or prevention of one or more metabolic disorders utilizing fatostatin A and/or a derivative and/or analog thereof. In other aspects, the compound for treatment and/or prevention of one or more metabolic disorders utilizes an A-B-C tripartite structure, wherein A, B, and C are identical or non-identical structures and are described in detail herein. In specific aspects, the metabolic disorder includes obesity or diabetes, for example.

The present invention highlights the role of acetyl-CoA carboxylase through its product malonyl-CoA in regulating fatty acid oxidation and synthesis, glucose metabolism and energy homeostasis. It discloses transgenic mice with inactivating mutations in the endogenous gene for the acetyl-CoA carboxylase 2 isoform of acetyl-CoA carboxylase. Inactivation of acetyl-CoA carboxylase 2 results in mice exhibiting a phenotype of reduced malonyl-CoA levels in skeletal muscle and heart, unrestricted fat oxidation, and reduced fat accumulation in the liver and fat storage cells. As a result, the mice consume more food but accumulate less fat and remain leaner than wild-type mice fed the same diet. The instant invention provides a useful animal model to regulate malonyl-CoA production by ACC2 in the regulation of fatty acid oxidation by muscle, heart, liver and other tissues. They also identify potential inhibitors for studying the mechanisms of fat metabolism and weight control.

Acetyl-coenzyme A carboxylase 2 as a target in the regulation of fat burning, fat accumulation, energy homeostasis and insulin action

The present invention discloses transgenic mice with inactivating mutations in the endogenous gene for the acetyl-CoA carboxylase-2 isoform of acetyl-CoA carboxylase. Inactivation of acetyl-CoA carboxylase-2 results in mice exhibiting a phenotype of reduced malonyl-CoA levels in skeletal muscle and heart, unrestricted fat oxidation, and reduced fat accumulation in the liver and fat storage cells. As a result, the mice consume more food but accumulate less fat and remain leaner than wild type mice fed the same diet. These results demonstrate that inhibition of ACC2 acetyl-CoA carboxylase could be used to regulate fat oxidation and accumulation for purposes of weight control. The transgenic mice of the instant invention provide a useful animal model to identify such inhibitors and for studying the mechanisms of fat metabolism and weight control.

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Houston, TX, United States of America

Salih J Wakil