Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage

Takeshi Nishikawa, Diane Edelstein, Xue Du, +9

Nature

Metabolic SyndromeBiochemistryMitochondrial FunctionHyperglycaemic DamageLipid Peroxidation +9

X-Ray Crystallographic and Kinetic Studies of Human Sorbitol Dehydrogenase

Thomas Pauly, J.L. Ekstrom, David A. Beebe, +14

Structure

Human Sorbitol DehydrogenaseBioanalysisAlcohol DehydrogenasesBiochemistry

Acetyl-CoA Carboxylase Inhibition Improves Multiple Dimensions of NASH Pathogenesis in Model Systems

Trenton T. Ross, Collin Crowley, Kenneth L. Kelly, +13

Cellular and Molecular Gastroenterology and Hepatology

Pyridones as glucokinase activators: Identification of a unique metabolic liability of the 4-sulfonyl-2-pyridone heterocycle

Jeffrey A. Pfefferkorn, Jihong Lou, Martha L. Minich, +14

Bioorganic & Medicinal Chemistry Letters

Unique Metabolic LiabilityBiochemistryMedicineMechanism Of ActionGlucokinase Activators +8

A Highly Selective, Non-Hydantoin, Non-Carboxylic Acid Inhibitor of Aldose Reductase with Potent Oral Activity in Diabetic Rat Models:  6-(5-Chloro-3-methylbenzofuran- 2-sulfonyl)-2-<i>H</i>-pyridazin-3-one

Banavara L. Mylari, Sandra J. Armento, David A. Beebe, +10

Journal of Medicinal Chemistry

Oral BioavailabilityAldo-keto ReductaseGlycobiologyMetabolic SyndromePotent Oral Activity +15

Designing glucokinase activators with reduced hypoglycemia risk: discovery of N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)-carbamoyl)benzofuran-4-yloxy)pyrimidine-2-carboxamide as a clinical candidate for the treatment of type 2 diabetes mellitus

Jeffrey A. Pfefferkorn, Angel Guzmán-Pérez, Peter J. Oates, +53

MedChemComm

A Novel Series of Non-Carboxylic Acid, Non-Hydantoin Inhibitors of Aldose Reductase with Potent Oral Activity in Diabetic Rat Models:  6-(5-Chloro-3-methylbenzofuran-2-sulfonyl)-2<i>H</i>-pyridazin-3-one and Congeners

Banavara L. Mylari, Sandra J. Armento, David A. Beebe, +10

Journal of Medicinal Chemistry

Medicinal ChemistryAldo-keto ReductaseBiochemistryMedicineAldose Reductase +13

Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK)

Kim Huard, Kay Ahn, Paul A. Amor, +30

Journal of Medicinal Chemistry

Metabolic SyndromeMedicinal ChemistryVivo InhibitionDrug TargetBiochemistry +12

Orally-Effective, Long-Acting Sorbitol Dehydrogenase Inhibitors:  Synthesis, Structure−Activity Relationships, and in Vivo Evaluations of Novel Heterocycle-Substituted Piperazino-Pyrimidines

Margaret Y. Chu‐Moyer, William E. Ballinger, David A. Beebe, +7

Journal of Medicinal Chemistry

PharmacotherapyPharmaceutical ChemistryVivo EvaluationsMedicinal ChemistrySorbitol Dehydrogenase +14

Spirolactam-Based Acetyl-CoA Carboxylase Inhibitors: Toward Improved Metabolic Stability of a Chromanone Lead Structure

David A. Griffith, Robert L. Dow, Kim Huard, +20

Journal of Medicinal Chemistry

Medicinal ChemistryChromanone Lead StructureBioorganic ChemistryPharmaceutical ChemistryBiochemistry +12