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2. Identification of small-molecule protein–protein interaction inhibitors for NKG2D

Author

Thompson, Aaron A., primary, Harbut, Michael B., additional, Kung, Pei-Pei, additional, Karpowich, Nathan K., additional, Branson, Jeffrey D., additional, Grant, Joanna C., additional, Hagan, Deborah, additional, Pascual, Heather A., additional, Bai, Guoyun, additional, Zavareh, Reza Beheshti, additional, Coate, Heather R., additional, Collins, Bernard C., additional, Côte, Marjorie, additional, Gelin, Christine F., additional, Damm-Ganamet, Kelly L., additional, Gholami, Hadi, additional, Huff, Adam R., additional, Limon, Luis, additional, Lumb, Kevin J., additional, Mak, Puiying A., additional, Nakafuku, Kohki M., additional, Price, Edmund V., additional, Shih, Amy Y., additional, Tootoonchi, Mandana, additional, Vellore, Nadeem A., additional, Wang, Jocelyn, additional, Wei, Na, additional, Ziff, Jeannie, additional, Berger, Scott B., additional, Edwards, James P., additional, Gardet, Agnès, additional, Sun, Siquan, additional, Towne, Jennifer E., additional, Venable, Jennifer D., additional, Shi, Zhicai, additional, Venkatesan, Hariharan, additional, Rives, Marie-Laure, additional, Sharma, Sujata, additional, Shireman, Brock T., additional, and Allen, Samantha J., additional

Published
2023
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6. Credit reporting and privacy issues.

Author

Hagan, Deborah

Subjects
Credit ratings -- Laws, regulations and rules, Liability for credit information -- Laws, regulations and rules, Fair Credit Reporting Act
Published
1992

10. Discovery of Dapagliflozin: A Potent, Selective Renal Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitor for the Treatment of Type 2 Diabetes

Author

Meng, Wei, primary, Ellsworth, Bruce A., additional, Nirschl, Alexandra A., additional, McCann, Peggy J., additional, Patel, Manorama, additional, Girotra, Ravindar N., additional, Wu, Gang, additional, Sher, Philip M., additional, Morrison, Eamonn P., additional, Biller, Scott A., additional, Zahler, Robert, additional, Deshpande, Prashant P., additional, Pullockaran, Annie, additional, Hagan, Deborah L., additional, Morgan, Nathan, additional, Taylor, Joseph R., additional, Obermeier, Mary T., additional, Humphreys, William G., additional, Khanna, Ashish, additional, Discenza, Lorell, additional, Robertson, James G., additional, Wang, Aiying, additional, Han, Songping, additional, Wetterau, John R., additional, Janovitz, Evan B., additional, Flint, Oliver P., additional, Whaley, Jean M., additional, and Washburn, William N., additional

Published
2008
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11. Dapagliflozin, a Selective SGLT2 Inhibitor, Improves Glucose Homeostasis in Normal and Diabetic Rats.

Author

Whaley, Jean, Hagan, Deborah, Taylor, Joseph, Li Xin, Songping Han, Wei Meng, Ellsworth, Bruce, Slier, Philip, McCann, Peggy, Gang Wu, Biller, Scott, Wetterau, John, and Washburn, William

Subjects
*ENZYME inhibitors, *HYPOGLYCEMIC agents, *GLUCOSE, *TREATMENT of diabetes, *GLUCOSE tolerance tests, *TYPE 2 diabetes, *ANIMAL disease models, *LABORATORY rats
Abstract

The inhibition of sodium-glucose transporters (SGLT) has been proposed as a novel therapeutic approach to treat diabetes. Relatively nonselective sodium-glucose cotransporter (SGLT) inhibitors such as phlorizin have been demonstrated to improve ambient plasma glucose levels as well as insulin sensitivity in diabetic animal models. Dapagliflozin (BMS-512148), a novel SGLT2 inhibitor under clinical investigation, selectively inhibits human SGLT2 vs. human SGLT1 in cell based assays (SGLT2 EC]sub 50] = 1.1 nM, SGLT1 EC[sub 50] = 1391 nM). In vivo, dapagliflozin acutely induces renal glucose excretion in normal and diabetic rats at doses of 0.1-1.0 mg/kg without hypoglycemia, improves glucose tolerance in normal rats at 1 and 10 mg/kg, and effectively lowers hyperglycemia in Zucker diabetic fatty (ZDF) rats following single oral doses ranging from 0.1-1.0 mg/kg. At a 1 mg/kg dose, the peak concentration of dapagliflozin in ZDF rat plasma was 1.2 µM with an area under the curve (AUC) over 6 hr of 5.2 µM*hr. In a 15 day study with 17 week old male ZDF rats, dapagliflozin treatment resulted in significantly lowered fasting and fed glucose levels at doses ranging from 0.1-1.0 mg/kg. Dapagliflozin treatment also improved key aspects of metabolic dysregulation in this model as evaluated in a hyperinsulinemic euglycemic clamp procedure. A significant increase in glucose infusion rate (GIR) was accompanied by a significant reduction in hepatic glucose production (HGP) when measured on the third day following the final dose. These data suggest that dapagliflozin has the potential to be an efficacious treatment for human type 2 diabetes. [ABSTRACT FROM AUTHOR]

Published
2007

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