The acronym stands for general unrestricted structureactivity relationships. Novel members of quinoline compound family enhance insulin secretion in rin5ah beta cells and in rat pancreatic islet microtissue. Structure activity relationship 6 linkedin slideshare. The repo rt and recommendations of ecvam workshop 52. Exenatide once weekly is contraindicated in patients with a personal or family history of medullary thyroid carcinoma, due to an increased incidence of thyroid cell tumors seen in animal. Sitespecific pegylation of exenatide analogues markedly. Pdf stability of exenatide in polyd,llactidecoglycolide.
With the discovery of tzds as the potent synthetic agonists, fatty acids and their derivatives as natural ligands of ppar. The present study provides an important basis for further analysis of structure activity relationship to develop optimized leads from bitter melon for the treatment of insulin resistance and obesity, they conclude. The exenatide products on the market, twicedaily byetta and onceweekly bydureon both amylin pharmaceuticals, san diego, ca, usa, are still not perfect. The researchers note that there may be as many as 70 active compounds in bitter melon. Sar and computeraided drug design approaches in the. Structure activity relationship sar is an approach designed to find relationships between chemical structure or structuralrelated properties and biological activity or target property of studied compounds. Applied regulatory science food and drug administration. It offers a secure access to gvk bios existing databases through an integrated, browserbased platform. The toxicity estimation software tool test was developed to allow users to easily estimate the toxicity of chemicals using quantitative structure activity relationships qsars methodologies. Though most commonly diagnosed in the elderly, younger adults and even children are increasingly subject to. Exenatide pregnancy registry type 2 diabetes in pregnancy.
Exenatide pregnancy registry type 2 diabetes in pregnancy exenatide the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. To discuss the ideal pharmacokinetic profile of exenatide for antiobesity effects, the relationship between the daily area under the plasma concentrationtime curve auc of exenatide for. Qsar for beginners free software for drug designing and. We here report a series of derivatives describing the structure. Basic studies have shown that glucagonlike peptide1 glp1 analogs exert a direct protective effect on the vascular endothelium in addition to their indirect effects on postprandial. Exenatide is administered subcutaneously and mimics human glucagonlike peptide1 glp1. Exenatide is a 39 amino acid peptide and synthetic version of exendin4, a hormone found in the saliva of the venomous lizard gila monster, with insulin secretagogue and antihyperglycemic activity. Structureactivity relationship sar analysis software programs, such as oncologic and multicase mcase, work by analyzing the chemical structure of a compound of unknown toxicity and predicting its likelihood to be a carcinogen based on comparisons to the structures of compounds with known toxicity and programmed chemical and. The exenatide study of cardiovascular event lowering exscel is a trial that assessed the longterm cardiovascular safety and efficacy of onceweekly exenatide, administered in patients with type 2. Circular dichroism cd cd spectroscopy jasco j810 spectrometer, jasco, tokyo, japan was exerted to investigate the secondary structure of exenatide in plga microsphere. Docking and qsar based screening of some naturally occurring diterpenes as inhibitors of angiotensin converting enzyme ace against cardiovascular diseases. Bydureon exscel trial meets primary safety objective in. Exenatide once weekly is contraindicated in patients with a personal or family history of medullary thyroid carcinoma, due to an increased incidence of thyroid cell tumors seen in animal studies. It works by stimulating the pancreas to secrete insulin when blood sugar levels are.
Pharmaceutics free fulltext effect of stabilizers on. The exenatide study of cardiovascular event lowering exscel is a trial that assessed the longterm cardiovascular safety and efficacy of onceweekly exenatide, administered in patients with type 2 diabetes who had a wide range of cardiovascular risk. Jan 19, 2011 the acute glucoregulatory activity of exenatide and pb. Although most of the available chemoinformatic software packages provide routines for the calculation of descriptors they are not easy to use in most cases. Novel members of quinoline compound family enhance insulin. Effects of exenatide on postprandial vascular endothelial. A major goal of quantitative structure activity relationship qsar quantitative structure property relationship qspr studies is to find a mathematical relationship between the activity or property. It is one of the most important techniques in comparability studies of biologics and a key step in the characterization of biopharmaceutical proteins.
Exenatide derived from the saliva of the gila monster, is a 39 amino acid peptide that mimics the glp1 incretin, an insulin secretagogue with glucoregulatory effects. Though most commonly diagnosed in the elderly, younger adults and even children are increasingly subject to the disease. Exenatide is an injectable drug that reduces the level of sugar glucose in the blood. To discuss the ideal pharmacokinetic profile of exenatide for antiobesity effects, the relationship between the daily area under the plasma concentrationtime curve auc of exenatide for plasma and bodyweight reduction after multiple subcutaneous administrations and subcutaneous infusion for 2 weeks was simulated by the pkpd model. Exenatide prolongedrelease suspension for injection in. A key step in classical quantitative structureactivity property relationship. Structureactivity relationship sar is an approach designed to find relationships between chemical structure or structuralrelated properties and biological activity or target property of studied. Frontiers the effect of exenatide on cardiovascular risk. Structural stabilitychromatographic retention relationship on exenatide diastereomer separation article pdf available in analytical and bioanalytical chemistry 4048. Gvk bio online structure activity relationship database gvk biosciences private limited about gostar gostar gvk bio online structure activity relationship database is an online scientific database product of gvk bio. Exenatide has been shown to be effective at improving insulin sensitivity and weight loss in pcos. Biological activity, quantitative structureactivity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs isnatin miladiyah,1,2 jumina jumina,3 sofia mubarika haryana,4. Gusar is a tool to create models on quantitative structureactivity relationships. Exenatide belongs in a class of drugs called incretin mimetics because these drugs.
The system delivers insulin in a glucose responsive manner resulting in periods of euglycemia. A solution model can be used to elucidate drug stability issues in a complex system. Polycystic ovary syndrome pcos is associated with an adverse cardiovascular risk profile including a prothrombotic state. In this video, professor rury holman shares his insights into the trial results. Structure activity relationship sar is an approach to find qualitative relationships between chemical.
A major goal of quantitative structure activity relationship qsar quantitative structure property relationship qspr studies is to find a mathematical relationship between the activity or property under investigation, and one or more descriptive parameters or descriptors related to the structure of the molecule. However, it has a short plasma halflife and requires a twice daily injection regime. Jan 24, 2015 5 structure activity relationship the relationship between the chemical or 3d structure of a molecule and its biological activity. Qsars are mathematical models used to predict measures of toxicity from the physical characteristics of the structure of chemicals known as molecular. Structure activity relationships sar explore the relationship between a molecules biological activity and the three dimensional structure of the molecule. Structure activity relationship sar analysis software programs, such as oncologic and multicase mcase, work by analyzing the chemical structure of a compound of unknown toxicity and predicting its likelihood to be a carcinogen based on comparisons to the structures of compounds with known toxicity and programmed chemical and. Exenatide is in a class of medications called incretin mimetics. Exenatide is a 39aminoacid peptide widely used to manage type 2 diabetes mellitus.
Exenatide has been shown to be effective at improving insulin. A key step in classical quantitative structure activity property relationship qsarqspr modeling is the encoding of a chemical compound into a vector of numerical descriptors. The trial compared the effect of onceweekly bydureon exenatide extendedrelease versus placebo, when added to usual type2 diabetes care, on the risk of mace, a composite endpoint. Researching changes in a1c, weight and other factors through intervention with exenatide once weekly duration1 study, the safety and efficacy of 30 weeks of treatment with the glucagonlike peptide1 receptor agonist exenatide once weekly exenatide qw.
Sar study of the peptidebinding domains of the targeted enzyme and their associated interaction was performed using the pepsite 2 software trabuco et al. There is a relationship between molecular structures and their biological activity, and this principle is referred to as structure activity relationship sar. The present study provides an important basis for further analysis of structureactivity relationship to develop. A quantitative structureactivity and relationship qsar model is an analytical tool that can interpret the measurable relationships between a molecules structure and its biological activities. The spacer region between the fatty acid and the peptide is mostly important for potency, whereas the fatty acid or fatty acid mimetic is important for both potency.
Peptide mapping, the principal technique for confirming a proteins primary structure amino acid sequence, can be used in drug discovery and throughout the manufacturing process. Approximately 95% of all adults diagnosed with diabetes have type 2. Structure activity relationship sar studies for ppar. Adjuvant liraglutide and insulin versus insulin monotherapy. Structure activity relationship chemistry free software. Exenatide byetta for diabetes contraindications renal impaiment, egfr software, originlab corp, northampton, ma, usa and then processed with 7point smoothing. The liraglutide arm was associated with overall decreased mean bg levels p. Sep 22, 2017 a quantitative structureactivity and relationship qsar model is an analytical tool that can interpret the measurable relationships between a molecules structure and its biological activities.
The aim of this study was to investigate the interaction between polyd,llactidecoglycolide plga and. Structural stabilitychromatographic retention relationship on exenatide diastereomer separation article pdf available in analytical and bioanalytical chemistry. Listing a study does not mean it has been evaluated by the u. By continuing to browse this site you are agreeing to our use of cookies. The aim of this study was to investigate the effects of various stabilizers on the encapsulation efficiency and release of exenatideloaded plga polylacticcoglycolic acid microspheres prepared by the. Quantitative structure activity relationship and drug design.
Gvk bio online structure activity relationship database. Gi side effects, hypoglycemia with insulinsulfonylureas, renal insufficiency, in combination with prandial insulin not studied, increase anticoagulant monitoring of warfarin upon initiation and titration of. Gi side effects, hypoglycemia with insulinsulfonylureas, renal insufficiency, in combination with prandial insulin not studied, increase anticoagulant monitoring of warfarin upon initiation and titration of exenatide, use cause with narrow therapeutic index drugs or those requiring rapid absorption. Quantitative structure activity relationship and drug. Oddescriptors is a javabased instrument that is easytouse and can be accessed from the command line interface. If the target structure is known, computational chemistry and molecular modelling software packages can be useful in identifying binding site interactions. Sar tools like cdd vault can detect correlations and build models used to evaluate new chemical structures to predict their biological activity. Bydureon exscel trial meets primary safety objective in type.
Biological activity, quantitative structureactivity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs isnatin miladiyah,1,2 jumina jumina,3 sofia mubarika haryana,4 mustofa mustofa5 1pharmacology department, faculty of medicine, islamic university of indonesia, 2doctorate program of medical science and health, faculty of medicine, 3chemistry department. To overcome these drawbacks we used maleimidepolyethylene glycol to induce sitespecific. Although the amino acid sequence of exenatide shares 53% homology with human glp. Toxicity estimation software tool test safer chemicals. Structural stabilitychromatographic retention relationship. It was shown that the stabilizers affected exenatide stability in aqueous solutions, at waterdichloromethane interfaces, on. The input of the program is your training set of chemical structures and quantitative data on biological activities. May 23, 2017 the trial compared the effect of onceweekly bydureon exenatide extendedrelease versus placebo, when added to usual type2 diabetes care, on the risk of mace, a composite endpoint of cv death, nonfatal myocardial infarction or nonfatal stroke, in adults with type2 diabetes t2d at a wide range of cv risk. Many researchers have attempted to prolong the acting time of exenatide by preparing sustainedrelease dosage forms, modifying its structure, gene therapies, and other means. Biological activity, quantitative structureactivity. Exenatide belongs in a class of drugs called incretin mimetics because these drugs mimic the effects of incretins. The closedloop cl system has potential to change the lives of patients with type 1 diabetes.
828 290 1486 1070 531 793 593 1431 1354 851 959 1105 596 434 1276 124 1035 137 826 274 1323 552 499 1228 119 905 1030 1022 236 597 1429 4 571 701 1079 67 662 810