The Experts below are selected from a list of 34689 Experts worldwide ranked by ideXlab platform
Bernard Pirotte - One of the best experts on this subject based on the ideXlab platform.
-
three dimensional quantitative structure activity relationships of atp sensitive potassium katp channel openers belonging to the 3 alkylamino 4h 1 2 4 benzo and 3 alkylamino 4h 1 2 4 pyridothiadiazine 1 1 dioxide families
Journal of Medicinal Chemistry, 2006Co-Authors: Pascal De Tullio, L Dupont, Pierre Francotte, Stephane Counerotte, Philippe Lebrun, Bernard PirotteAbstract:Recent studies have demonstrated that selective activation of pancreatic ATP-sensitive potassium (KATP) channels could be of clinical value in the treatment of type I and type II diabetes, obesity, and hypersinsulinemia. Taking into account these promising therapeutic opportunities, we have explored the 3-alkylamino-4H-1,2,4-pyrido- and 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide families. Among these series, numerous Drugs were identified as highly potent and selective openers of either the pancreatic or the aortic KATP channels. Thanks to comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), quantitative structure-activity relationship approaches using more than 100 compounds, pharmacophoric models explaining the activity and selectivity of the Drugs have been elaborated. These models highlighted the importance of several chemical regions for KATP channel activation and could be very helpful for future improvement of Drug Potency, selectivity, or both. Moreover, an original CoMSIA analysis, using a selectivity index (SI) as a dependent variable, was also performed with the aim of identifying the structural parameters influencing tissue selectivity.
Peter D Senter - One of the best experts on this subject based on the ideXlab platform.
-
antibody Drug conjugates targeted Drug delivery for cancer
Current Opinion in Chemical Biology, 2010Co-Authors: Stephen C Alley, Nicole M Okeley, Peter D SenterAbstract:The antibody–Drug conjugate field has made significant progress recently owing to careful optimization of several parameters, including mAb specificity, Drug Potency, linker technology, and the stoichiometry and placement of conjugated Drugs. The underlying reason for this has been obtained in pre-clinical biodistribution and pharmacokinetics studies showing that targeted delivery leads to high intratumoral free Drug concentrations, while non-target tissues are largely spared from chemotherapeutic exposure. Recent developments in the field have led to an increase in the number of ADCs being tested clinically, with 3 in late stage clinical trials: brentuximab vedotin (also referred to as SGN-35) for Hodgkin lymphoma; Trastuzumab-DM1 for breast cancer; and Inotuzumab ozogamicin for non-Hodgkin lymphoma. This review highlights the recent pre-clinical and clinical advances that have been made.
-
Antibody-Drug conjugates for cancer therapy.
Cancer journal (Sudbury Mass.), 2008Co-Authors: Paul J Carter, Peter D SenterAbstract:The antibody-Drug conjugate (ADC) concept is to use an antibody to deliver a cytotoxic Drug selectively to a target such as a tumor-associated antigen. Such conjugates represent a broadly applicable approach to enhance the antitumor activity of antibodies and improve the tumor-to-normal tissue selectivity of chemotherapy. Critical parameters for ADC development include target antigen selection, conjugate internalization by tumor cells, Drug Potency and stability of the linker between Drug and antibody. Other important considerations include the conjugation methods, Drug-to-antibody ratio, and the effects of Drug conjugation on antibody properties. Highly potent Drugs with more stable linkers have been attached to a new generation of antibodies to create conjugates with pronounced antitumor activities in preclinical studies and encouraging results in early stage clinical trials. This review details these advances, discusses some of the remaining challenges, and overviews ADCs currently in clinical trials for cancer therapy.
-
selective activation of anticancer proDrugs by monoclonal antibody enzyme conjugates
Advanced Drug Delivery Reviews, 2001Co-Authors: Peter D Senter, Caroline J SpringerAbstract:A great deal of interest has surrounded the activities of monoclonal antibodies (mAbs), and mAb-Drug, toxin and radionuclide conjugates for the treatment of human cancers. In the last few years, a number of new mAb-based reagents have been clinically approved (Rituxan, Herceptin, and Panorex), and several others are now in advanced clinical trials. Successful therapeutic treatment of solid tumors with Drug conjugates of such macromolecules must overcome the barriers to penetration within tumor masses, antigen heterogeneity, conjugated Drug Potency, and efficient Drug release from the mAbs inside tumor cells. An alternative strategy for Drug delivery involves a two-step approach to cancer therapy in which mAbs are used to localize enzymes to tumor cell surface antigens. Once the conjugate binds to the cancer cells and clears from the systemic circulation, antitumor proDrugs are administered that are catalytically converted to active Drugs by the targeted enzyme. The Drugs thus released are capable of penetrating within the tumor mass and eliminating both cells that have and have not bound the mAb-enzyme conjugate. Significant therapeutic effects have been obtained using a broad range of enzymes along with proDrugs that are derived from both approved anticancer Drugs and highly potent experimental agents. This review focuses on the activities of several mAb-enzyme/proDrug combinations, with an emphasis on those that have provided mechanistic insight, clinical activity, novel protein constructs, and the potential for reduced immunogenicity.
Pascal De Tullio - One of the best experts on this subject based on the ideXlab platform.
-
three dimensional quantitative structure activity relationships of atp sensitive potassium katp channel openers belonging to the 3 alkylamino 4h 1 2 4 benzo and 3 alkylamino 4h 1 2 4 pyridothiadiazine 1 1 dioxide families
Journal of Medicinal Chemistry, 2006Co-Authors: Pascal De Tullio, L Dupont, Pierre Francotte, Stephane Counerotte, Philippe Lebrun, Bernard PirotteAbstract:Recent studies have demonstrated that selective activation of pancreatic ATP-sensitive potassium (KATP) channels could be of clinical value in the treatment of type I and type II diabetes, obesity, and hypersinsulinemia. Taking into account these promising therapeutic opportunities, we have explored the 3-alkylamino-4H-1,2,4-pyrido- and 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide families. Among these series, numerous Drugs were identified as highly potent and selective openers of either the pancreatic or the aortic KATP channels. Thanks to comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), quantitative structure-activity relationship approaches using more than 100 compounds, pharmacophoric models explaining the activity and selectivity of the Drugs have been elaborated. These models highlighted the importance of several chemical regions for KATP channel activation and could be very helpful for future improvement of Drug Potency, selectivity, or both. Moreover, an original CoMSIA analysis, using a selectivity index (SI) as a dependent variable, was also performed with the aim of identifying the structural parameters influencing tissue selectivity.
Philippe Lebrun - One of the best experts on this subject based on the ideXlab platform.
-
three dimensional quantitative structure activity relationships of atp sensitive potassium katp channel openers belonging to the 3 alkylamino 4h 1 2 4 benzo and 3 alkylamino 4h 1 2 4 pyridothiadiazine 1 1 dioxide families
Journal of Medicinal Chemistry, 2006Co-Authors: Pascal De Tullio, L Dupont, Pierre Francotte, Stephane Counerotte, Philippe Lebrun, Bernard PirotteAbstract:Recent studies have demonstrated that selective activation of pancreatic ATP-sensitive potassium (KATP) channels could be of clinical value in the treatment of type I and type II diabetes, obesity, and hypersinsulinemia. Taking into account these promising therapeutic opportunities, we have explored the 3-alkylamino-4H-1,2,4-pyrido- and 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide families. Among these series, numerous Drugs were identified as highly potent and selective openers of either the pancreatic or the aortic KATP channels. Thanks to comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), quantitative structure-activity relationship approaches using more than 100 compounds, pharmacophoric models explaining the activity and selectivity of the Drugs have been elaborated. These models highlighted the importance of several chemical regions for KATP channel activation and could be very helpful for future improvement of Drug Potency, selectivity, or both. Moreover, an original CoMSIA analysis, using a selectivity index (SI) as a dependent variable, was also performed with the aim of identifying the structural parameters influencing tissue selectivity.
L Dupont - One of the best experts on this subject based on the ideXlab platform.
-
three dimensional quantitative structure activity relationships of atp sensitive potassium katp channel openers belonging to the 3 alkylamino 4h 1 2 4 benzo and 3 alkylamino 4h 1 2 4 pyridothiadiazine 1 1 dioxide families
Journal of Medicinal Chemistry, 2006Co-Authors: Pascal De Tullio, L Dupont, Pierre Francotte, Stephane Counerotte, Philippe Lebrun, Bernard PirotteAbstract:Recent studies have demonstrated that selective activation of pancreatic ATP-sensitive potassium (KATP) channels could be of clinical value in the treatment of type I and type II diabetes, obesity, and hypersinsulinemia. Taking into account these promising therapeutic opportunities, we have explored the 3-alkylamino-4H-1,2,4-pyrido- and 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide families. Among these series, numerous Drugs were identified as highly potent and selective openers of either the pancreatic or the aortic KATP channels. Thanks to comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), quantitative structure-activity relationship approaches using more than 100 compounds, pharmacophoric models explaining the activity and selectivity of the Drugs have been elaborated. These models highlighted the importance of several chemical regions for KATP channel activation and could be very helpful for future improvement of Drug Potency, selectivity, or both. Moreover, an original CoMSIA analysis, using a selectivity index (SI) as a dependent variable, was also performed with the aim of identifying the structural parameters influencing tissue selectivity.
