Search results for "Drug development"
showing 10 items of 115 documents
89 Zr-Immuno-Positron Emission Tomography in Oncology: State-of-the-Art 89 Zr Radiochemistry
2017
Contains fulltext : 181624.pdf (Publisher’s version ) (Open Access) Immuno-positron emission tomography (immunoPET) with (89)Zr-labeled antibodies has shown great potential in cancer imaging. It can provide important information about the pharmacokinetics and tumor-targeting properties of monoclonal antibodies and may help in anticipating on toxicity. Furthermore, it allows accurate dose planning for individualized radioimmunotherapy and may aid in patient selection and early-response monitoring for targeted therapies. The most commonly used chelator for (89)Zr is desferrioxamine (DFO). Preclinical studies have shown that DFO is not an ideal chelator because the (89)Zr-DFO complex is partly…
Peptide microarrays enable rapid mimotope optimization for pharmacokinetic analysis of the novel therapeutic antibody IMAB362.
2014
As membrane proteins play an important role in a variety of life-threatening diseases, the development of therapeutic monoclonal antibodies against membrane proteins is of significant interest. Among many other requirements, the process of antibody drug development requires a set of tailor-made assays for the characterization of the antibodies and for monitoring their activity. Designing assays to characterize antibodies directed to membrane proteins is challenging, because the natural targets are often not available in a format that is compatible with a biochemical assay setup. Thus, alternatives that mimic the targeted membrane proteins are needed. In this study, we developed optimal pept…
Combining the wisdoms of traditional medicine with cutting-edge science and technology at the forefront of medical sciences
2019
Abstract Background A central topic is to bring traditional medicine to a new horizon by integrating the latest advances in genomic, metabolomic, and system biological approaches, in order to re-examine the wisdom and knowledge of traditional Chinese medicine (TCM) and other traditional medicines. Purpose A new consortium has been formed at a conference of the Harvard Medical School, Boston, on October 29–30, 2018. The main goal was to build a collaborative platform for the scientific investigation of traditional medicine with cutting edge sciences and technologies at the forefront of biomedicine. Results Traditional medicines are largely experience-based, but the scientific basis is largel…
The use of porous and surface modified silicas as drug delivery and stabilizing agents
1983
(1983). The use of porous and surface modified silicas as drug delivery and stabilizing agents. Drug Development and Industrial Pharmacy: Vol. 9, No. 1-2, pp. 69-91.
QRAR models for central nervous system drugs using biopartitioning micellar chromatography.
2002
The capability of biopartitioning Micellar Chromatography, BMC, to describe and estimate pharmacokinetic and pharmacodynamic parameters of central nervous system drugs is reviewed in this article. BMC is a mode of micellar liquid chromatography, MLC, that uses micellar mobile phases of Brij35 (polyoxyethilene(23) lauryl ether) prepared in physiological conditions (pH, ionic strength). The retention of a drug in this system depends on its hydrophobic, electronic and steric properties, which also determine its biological activity. The results of BMC studies suggest that this in vitro approach is an attractive useful tool to be implemented into the lead optimization step of drug development sc…
An update on metabolism studies using human hepatocytes in primary culture
2008
Background: Cultured human hepatocytes are the closest in vitro model to human liver and constitute a very predictive model for drug metabolism in vivo. The variability observed in human hepatocytes reflects the existing phenotypic heterogeneity of cytochrome P450 expression in human liver. Objectives: As drug metabolism is the major source of pharmacokinetic variability in human beings, the main areas of current drug metabolism research in human hepatocytes are reviewed. Methods: To speed up the selection of drug candidates, the evaluation of metabolic stability, metabolite profiling and identification, and drug–drug interaction potential are key issues in drug development. Results/conclus…
Antioxidants as treatment for neurodegenerative disorders.
2002
Oxidative stress is a ubiquitously observed hallmark of neurodegenerative disorders. Neuronal cell dysfunction and cell death due to oxidative stress may causally contribute to the pathogenesis of progressive neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, as well as acute syndromes of neurodegeneration, such as ischaemic and haemorrhagic stroke. Neuroprotective antioxidants are considered a promising approach to slowing the progression and limiting the extent of neuronal cell loss in these disorders. The clinical evidence demonstrating that antioxidant compounds can act as protective drugs in neurodegenerative disease, however, is still relatively scarce. …
Transcriptional regulation and expression of CYP3A4 in hepatocytes.
2007
CYP3A4 is the most abundantly expressed drug-metabolizing P450 enzyme in human liver and contributes to the metabolism of a large number of drugs in use today. CYP3A4 is constitutively expressed in adult hepatocytes but it can also be transcriptionally induced by a variety of structurally diverse xenochemicals. CYP3A4 strongly contributes to the important variability in the therapeutic and toxic effects of drugs owing to the major role it plays in xenobiotic metabolism and the large intra- and inter-individual variability to which it is subjected. The functional examination of up to 13 kb of the CYP3A4 5'-flanking region has revealed that the regulation of this gene is a complex issue, with…
Toward the Discovery of New Agents Able to Inhibit the Expression of Microsomal Prostaglandin E Synthase-1 Enzyme as Promising Tools in Drug Developm…
2010
In our recent studies, we focused our attention on the synthesis of several γ-hydroxybutenolides designed on the basis of petrosaspongiolide M 1 (PM) structure that has been recognized to potently inhibit the inflammatory process through the selective PLA2 enzyme inhibition. By means of a combination of computational methods and efficient synthetic strategies, we generated small collections of PM modified analogs to identify new potent PLA2 inhibitors, suitable for clinical development. In the course of the biological screening of our compounds, we discovered a potent and selective inhibitor of mPGES-1 expression, the benzothiophene γ-hydroxybutenolide 2, which so far represents the only pr…
mRNA-based therapeutics — developing a new class of drugs
2014
In vitro transcribed (IVT) mRNA has recently come into focus as a potential new drug class to deliver genetic information. Such synthetic mRNA can be engineered to transiently express proteins by structurally resembling natural mRNA. Advances in addressing the inherent challenges of this drug class, particularly related to controlling the translational efficacy and immunogenicity of the IVTmRNA, provide the basis for a broad range of potential applications. mRNA-based cancer immunotherapies and infectious disease vaccines have entered clinical development. Meanwhile, emerging novel approaches include in vivo delivery of IVT mRNA to replace or supplement proteins, IVT mRNA-based generation o…