scholarly journals Bioanalysis and pharmacokinetic studies

2020 ◽  
pp. IPK01
Author(s):  
Maria Veneziano
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Bioanalytical Methods ◽  
High Resolution Mass Spectrometry ◽  
Drug Candidate ◽  
Pharmacokinetic Studies ◽  
Inborn Errors ◽  
Drug Discovery Program

Biography: Maria Veneziano is currently a Research Investigator in the DMPK unit at IRBM (Pomezia, Italy), an Italian CRO and biotech company specializing in preclinical drug discovery of small molecules, peptides and antibodies. She studied Biological Science at ‘Federico II’ University of Naples (Italy) and completed her PhD in Medical Biotechnologies at Merck Research Laboratories (MRL) in Rome (Italy) developing bioanalytical methods used to identify and quantify amino acids and acylcarnitines for the diagnosis and follow-up of inborn errors of metabolism. As part of the DMPK team at MRL, she was involved in PK and ADME profiling of small molecule and peptide candidates for drug-discovery programs. Presently, Maria leads a group supporting PK and PK/PD studies for small molecules and peptides. Maria Veneziano speaks to the International Journal of Pharmacokinetics about her experience working on pharmacokinetic studies. She starts by discussing the conventional bioanalytical methods used for the quantitative analysis of small molecules and peptides and she highlights the important role of LC–MS detection and sample preparation in the bioanalysis of pharmacokinetic studies. She also speaks about the role of high-resolution mass spectrometry in the bioanalysis of peptides as an important tool in a drug-discovery program to simultaneously define pharmacokinetic and metabolic profiles of the same drug candidate. She also describes cassette dosing and cassette analysis approaches as strategies to increase sample throughput, highlighting advantages and limits of each of these strategies. Finally, Maria speaks about her idea of ‘simplified PK workflow’ based on the miniaturization and automation of all the steps in a PK study, from in vivo administration to sample analysis.

scholarly journals PET Imaging Radiotracers of Chemokine Receptors

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5174
Author(s):  
Santosh R. Alluri ◽  
Yusuke Higashi ◽  
Kun-Eek Kil
Keyword(s):  
Small Molecules ◽  
Chemokine Receptors ◽  
Brain Disorders ◽  
Infectious Agents ◽  
Cardiovascular Research ◽  
Critical Signal ◽  
Inflammatory Reactions ◽  
Positron Emission

Chemokines and chemokine receptors have been recognized as critical signal components that maintain the physiological functions of various cells, particularly the immune cells. The signals of chemokines/chemokine receptors guide various leukocytes to respond to inflammatory reactions and infectious agents. Many chemokine receptors play supportive roles in the differentiation, proliferation, angiogenesis, and metastasis of diverse tumor cells. In addition, the signaling functions of a few chemokine receptors are associated with cardiac, pulmonary, and brain disorders. Over the years, numerous promising molecules ranging from small molecules to short peptides and antibodies have been developed to study the role of chemokine receptors in healthy states and diseased states. These drug-like candidates are in turn exploited as radiolabeled probes for the imaging of chemokine receptors using noninvasive in vivo imaging, such as positron emission tomography (PET). Recent advances in the development of radiotracers for various chemokine receptors, particularly of CXCR4, CCR2, and CCR5, shed new light on chemokine-related cancer and cardiovascular research and the subsequent drug development. Here, we present the recent progress in PET radiotracer development for imaging of various chemokine receptors.

Role of Pharmacokinetic Studies in Drug Discovery

2011 ◽  
Vol 03 (11) ◽  
Author(s):  
Nishant Toomula ◽  
Sathish Kumar D ◽  
Arun Kumar ◽  
Phaneendra M
Keyword(s):  
Drug Discovery ◽  
Pharmacokinetic Studies

scholarly journals Mining the Information for Structure Based Drug Designing by Relational Database Management Notion

2009 ◽  
Vol 6 (4) ◽  
pp. 1047-1054
Author(s):  
R. Balajee ◽  
M. S. Dhanarajan
Keyword(s):  
Drug Discovery ◽  
Drug Targets ◽  
Three Dimensional ◽  
Chemical Properties ◽  
Structure Based Drug Design ◽  
Molecular Systems ◽  
Drug Discovery Program ◽  
And Behavior

Structure based drug design is a technique that is used in the initial stages of a drug discovery program. The role of various computational methods in the characterization of the chemical properties and behavior of molecular systems is discussed. The field of bioinformatics has become a major part of the drug discovery pipeline playing a key role for validating drug targets. By integrating data from many inter-related yet heterogeneous resources, informatics can help in our understanding of complex biological processes and help improve drug discovery. The determination of the three dimensional properties of small molecules and macromolecular receptor structures is a core activity in the efforts towards a better understanding of structure-activity relationships.

NMR spectroscopy in drug design

2001 ◽  
Vol 73 (9) ◽  
pp. 1429-1436 ◽  
Author(s):  
Markus Heller ◽  
Horst Kessler
Keyword(s):  
Small Molecules ◽  
Lead Optimization ◽  
Drug Candidate ◽  
Resonance Spectroscopy ◽  
Ligand Complex ◽  
New Techniques ◽  
Lead Finding ◽  
Efficient Screening ◽  
Insight Into

The process of preclinical drug discovery consists of two steps: finding of initial hits (binding ligands to a medicinal relevant target, usually a protein) and lead optimization. Nuclear magnetic resonance spectroscopy is a powerful tool that can provide valuable information to every step of drug development. NMR is commonly used for characterizing the structure and molecular dynamics of target or ligand molecules. During the structure-based lead optimization, NMR provides insight into the structural and dynamical properties of the target-ligand complex. Recently, the use of NMR in the lead finding process by screening technologies has been shown. For the latter use, new techniques have also been developed. Those techniques, in combination with high throughput, have lead to an efficient screening of libraries composed of small molecules. In this article, the role of NMR during the discovery of a drug candidate is described.

Double Lumen Needle in Unipuncture Dialysis Type Double Headpump

1981 ◽  
Vol 4 (2) ◽  
pp. 72-74 ◽  
Author(s):  
R. Vanholder ◽  
M. De Paepe ◽  
N.A. Hoenich ◽  
S. Ringoir ◽  
A. De Cubber ◽  
...  
Keyword(s):  
Small Molecules ◽  
Vascular Access ◽  
In Vitro Studies ◽  
Double Lumen ◽  
Single Lumen

Single needle dialysis is used as a method of vascular access in many European dialysis centres. However, recirculation has been incriminated as a disadvantage of this procedure. According to in vitro studies, recirculation should be limited to a minimum when using double lumen needles. The present study makes an in vivo comparison between single and double lumen needles in unipuncture (single needle) dialysis of the type double headpump (Bellco, BL 760) and studies the role of recirculation in dialysis performance. Although recirculation is significantly reduced with the double lumen needle, compared to the single lumen needle, the clearance of small molecules is not significantly different for both needle types.

scholarly journals Mycobacterium tuberculosis Gyrase Inhibitors as a New Class of Antitubercular Drugs

2015 ◽  
Vol 59 (4) ◽  
pp. 1868-1875 ◽  
Author(s):  
Delia Blanco ◽  
Esther Perez-Herran ◽  
Mónica Cacho ◽  
Lluís Ballell ◽  
Julia Castro ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Discovery ◽  
Oral Absorption ◽  
Cell Activity ◽  
Cross Resistance ◽  
Drug Candidate ◽  
Antibacterial Drug ◽  
Gyrase Inhibitors

ABSTRACTOne way to speed up the TB drug discovery process is to search for antitubercular activity among compound series that already possess some of the key properties needed in anti-infective drug discovery, such as whole-cell activity and oral absorption. Here, we present MGIs, a new series ofMycobacterium tuberculosisgyrase inhibitors, which stem from the long-term efforts GSK has dedicated to the discovery and development of novel bacterial topoisomerase inhibitors (NBTIs). The compounds identified were found to be devoid of fluoroquinolone (FQ) cross-resistance and seem to operate through a mechanism similar to that of the previously described NBTI GSK antibacterial drug candidate. The remarkablein vitroandin vivoantitubercular profiles showed by the hits has prompted us to further advance the MGI project to full lead optimization.

Role of Phytochemicals in the Prevention of Menopausal Bone Loss: Evidence from In Vitro and In Vivo, Human Interventional and Pharmacokinetic Studies

2009 ◽  
Vol 16 (9) ◽  
pp. 1138-1157 ◽  
Author(s):  
Kunal Sharan ◽  
Jawed Siddiqui ◽  
Gaurav Swarnkar ◽  
Rakesh Maurya ◽  
Naibedya Chattopadhyay
Keyword(s):  
Bone Loss ◽  
Pharmacokinetic Studies

scholarly journals Recent insights into the role of the contact pathway in thrombo-inflammatory disorders

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 60-65 ◽  
Author(s):  
Maurits L. van Montfoort ◽  
Joost C.M. Meijers
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Antisense Oligonucleotides ◽  
Contact System ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Vascular Beds ◽  
Contact Pathway

Abstract The contact pathway of coagulation consists of the proteins factor XI, factor XII, prekallikrein, and high-molecular-weight kininogen. Activation of the contact system leads to procoagulant and proinflammatory reactions. The contact system is essential for surface-initiated coagulation, as exemplified by aPTT, but there is probably no role for the contact system in initiating physiologic in vivo coagulation. However, over the last few years, there has been renewed interest, especially because of experimental evidence suggesting that the contact system contributes to thrombosis. Knockout mice deficient in one of the contact proteins were protected against artificially induced thrombosis. Furthermore, inhibiting agents such as monoclonal antibodies, antisense oligonucleotides, and small molecules were found to prevent thrombosis in rodents and primates in both venous and arterial vascular beds. Although it remains to be established whether targeting the contact system will be effective in humans and which of the contact factors is the best target for anticoagulation, it would constitute a promising approach for future effective and safe antithrombotic therapy.

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