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Wei Meng

Bio: Wei Meng is an academic researcher from Bristol-Myers Squibb. The author has contributed to research in topics: Aryl & Hyperinsulinemia. The author has an hindex of 16, co-authored 49 publications receiving 2195 citations.


Papers
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Journal ArticleDOI
TL;DR: The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats.
Abstract: The C-aryl glucoside 6 (dapagliflozin) was identified as a potent and selective hSGLT2 inhibitor which reduced blood glucose levels in a dose-dependent manner by as much as 55% in hyperglycemic streptozotocin (STZ) rats. These findings, combined with a favorable ADME profile, have prompted clinical evaluation of dapagliflozin for the treatment of type 2 diabetes.

571 citations

Journal ArticleDOI
01 Jun 2008-Diabetes
TL;DR: In vivo and in vitro data suggest that dapagliflozin has the potential to be an efficacious treatment for type 2 diabetes.
Abstract: OBJECTIVE— The inhibition of gut and renal sodium-glucose cotransporters (SGLTs) has been proposed as a novel therapeutic approach to the treatment of diabetes. We have identified dapagliflozin as a potent and selective inhibitor of the renal sodium-glucose cotransporter SGLT2 in vitro and characterized its in vitro and in vivo pharmacology. RESEARCH DESIGN AND METHODS— Cell-based assays measuring glucose analog uptake were used to assess dapagliflozin's ability to inhibit sodium-dependent and facilitative glucose transport activity. Acute and multi-dose studies in normal and diabetic rats were performed to assess the ability of dapagliflozin to improve fed and fasting plasma glucose levels. A hyperinsulinemic-euglycemic clamp study was performed to assess the ability of dapagliflozin to improve glucose utilization after multi-dose treatment. RESULTS— Dapagliflozin potently and selectively inhibited human SGLT2 versus human SGLT1, the major cotransporter of glucose in the gut, and did not significantly inhibit facilitative glucose transport in human adipocytes. In vivo, dapagliflozin acutely induced renal glucose excretion in normal and diabetic rats, improved glucose tolerance in normal rats, and reduced hyperglycemia in Zucker diabetic fatty (ZDF) rats after single oral doses ranging from 0.1 to 1.0 mg/kg. Once-daily dapagliflozin treatment over 2 weeks significantly lowered fasting and fed glucose levels at doses ranging from 0.1 to 1.0 mg/kg and resulted in a significant increase in glucose utilization rate accompanied by a significant reduction in glucose production. CONCLUSIONS— These data suggest that dapagliflozin has the potential to be an efficacious treatment for type 2 diabetes.

377 citations

Patent
15 May 2003
TL;DR: In this article, an SGLT2 inhibiting compound is provided having the formula having the chemical structure, and a method is also provided for treating diabetes and related diseases employing an sGLT 2 inhibiting amount of the above compound alone or in combination with another antidiabetic agent or other therapeutic agent.
Abstract: An SGLT2 inhibiting compound is provided having the formula[Chemical structure] A method is also provided for treating diabetes and related diseases employing an SGLT2 inhibiting amount of the above compound alone or in combination with another antidiabetic agent or other therapeutic agent.

327 citations

Patent
02 Oct 2000
TL;DR: In this paper, a method for treating diabetes and related diseases employing an SGLT2 inhibiting amount of the above compound alone or in combination with another antidiabetic agent or other therapeutic agent.
Abstract: SGLT2 inhibiting compounds are provided having formula (I) where R?1, R2, and R2a? are independently hydrogen, OH, OR5, lower alkyl, CF?3?, OCHF2, OCF3, SR?5i? or halogen, or two of R?1, R2 and R2a? together with the carbons to which they are attached can form an annelated five, six or seven membered carbocycle or heterocycle; R?3 and R4? are independently hydrogen, OH, OR5a, OAryl, OCH?2?Aryl, lower alkyl, cycloalkyl, CF3, -OCHF2, -OCF3, halogen, -CN, -CO2R?5b, -CO?2H, -COR6b, -CH(OH)R6c, -CH(OR?5h)R6d, -CONR6R6a?, -NHCOR5c, -NHSO?2R?5d, -NHSO?2?Aryl, Aryl, -SR?5e, -SOR5f, SO?2R5g, SO2Aryl, or a five, six or seven membered heterocycle, or R?3 and R4? together with the carbons to which they are attached form an annelated five, six or seven membered carbocycle or heterocycle; R?5, R5a, R5b, R5c, R5d, R5e, R5f, R5g, R5h, and R5I? are independently lower alkyl; R?6, R6a, R6b, R6c and R6d? are independently hydrogen, alkyl, aryl, alkylaryl or cycloalkyl, or R?6 and R6a? together with the nitrogen to which they are attached form an annelated five, six or seven membered heterocycle; A is O, S, NH, or (CH?2?)n where n is 0 - 3. A method is also provided for treating diabetes and related diseases employing an SGLT2 inhibiting amount of the above compound alone or in combination with another antidiabetic agent or other therapeutic agent.

182 citations

Journal ArticleDOI
TL;DR: Pharmacokinetic parameters for dapagliflozin in preclinical species revealed a compound with adequate oral exposure, clearance, and elimination half-life, consistent with the potential for single daily dosing in humans.
Abstract: (2 S ,3 R ,4 R ,5 S ,6 R )-2-(3-(4-Ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyl-tetrahydro-2 H -pyran-3,4,5-triol (dapagliflozin; BMS-512148) is a potent sodium-glucose cotransporter type II inhibitor in animals and humans and is currently under development for the treatment of type 2 diabetes. The preclinical characterization of dapagliflozin, to allow compound selection and prediction of pharmacological and dispositional behavior in the clinic, involved Caco-2 cell permeability studies, cytochrome P450 (P450) inhibition and induction studies, P450 reaction phenotyping, metabolite identification in hepatocytes, and pharmacokinetics in rats, dogs, and monkeys. Dapagliflozin was found to have good permeability across Caco-2 cell membranes. It was found to be a substrate for P-glycoprotein (P-gp) but not a significant P-gp inhibitor. Dapagliflozin was not found to be an inhibitor or an inducer of human P450 enzymes. The in vitro metabolic profiles of dapagliflozin after incubation with hepatocytes from mice, rats, dogs, monkeys, and humans were qualitatively similar. Rat hepatocyte incubations showed the highest turnover, and dapagliflozin was most stable in human hepatocytes. Prominent in vitro metabolic pathways observed were glucuronidation, hydroxylation, and O -deethylation. Pharmacokinetic parameters for dapagliflozin in preclinical species revealed a compound with adequate oral exposure, clearance, and elimination half-life, consistent with the potential for single daily dosing in humans. The pharmacokinetics in humans after a single dose of 50 mg of [ 14 C]dapagliflozin showed good exposure, low clearance, adequate half-life, and no metabolites with significant pharmacological activity or toxicological concern.

156 citations


Cited by
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Journal ArticleDOI
TL;DR: Compounds Currently in Phase II−III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas is presented.
Abstract: Compounds Currently in Phase II−III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas Yu Zhou,† Jiang Wang,† Zhanni Gu,† Shuni Wang,† Wei Zhu,† Jose ́ Luis Aceña,*,‡,§ Vadim A. Soloshonok,*,‡,∥ Kunisuke Izawa,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastiań, Spain Department of Organic Chemistry, Autońoma University of Madrid, Cantoblanco, 28049 Madrid, Spain IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, 48013 Bilbao, Spain Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka, Japan 533-0024

1,740 citations

Patent
11 Jan 2011
TL;DR: In this article, an intelligent automated assistant system engages with the user in an integrated, conversational manner using natural language dialog, and invokes external services when appropriate to obtain information or perform various actions.
Abstract: An intelligent automated assistant system engages with the user in an integrated, conversational manner using natural language dialog, and invokes external services when appropriate to obtain information or perform various actions. The system can be implemented using any of a number of different platforms, such as the web, email, smartphone, and the like, or any combination thereof. In one embodiment, the system is based on sets of interrelated domains and tasks, and employs additional functionally powered by external services with which the system can interact.

1,462 citations

Journal ArticleDOI
TL;DR: A personal review of advances in the genetics, molecular biology, biochemistry, biophysics, and structure of SGLTs, including cotransporters for sugars, anions, vitamins, and short-chain fatty acids.
Abstract: There are two classes of glucose transporters involved in glucose homeostasis in the body, the facilitated transporters or uniporters (GLUTs) and the active transporters or symporters (SGLTs). The ...

1,082 citations

Patent
29 Oct 2007
TL;DR: The present invention encompasses albumin fusion proteins as discussed by the authors, as well as vectors containing these nucleic acids, host cells transformed with the nucleic acid vectors, and methods of making the fusion proteins of the invention.
Abstract: The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

998 citations

Journal ArticleDOI
TL;DR: Addition of dapagliflozin to meetformin provides a new therapeutic option for treatment of type 2 diabetes in patients who have inadequate glycaemic control with metformin alone.

783 citations