In contrast to earlier attempts for the identification of target candidates suitable for monoclonal antibody (mAb) based cancer therapies we concentrated on highly selective lineage-specific genes additionally preserved or even overexpressed in orthotopic cancers. In a script aided workflow we reduced all human entries of the RefSeq mRNA database to those encoding transmembrane domain bearing gene products and subjected them to BLAST analysis against the human EST database. All BLAST results were validated in a gene centric way allowing two types of data curation prior to expression profiling of matching ESTs in selected healthy tissues: (i) exclusion of questionable ESTs arising e.g. from genomic contamination and (ii) elimination of erroneously predicted mRNAs as well as transcripts with only weak EST coverage. The impact of such stringent input control on accuracy of prediction is underlined by RT-PCR confirmation of predicted tissue distribution patterns for a number of selected candidates.
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http://dx.doi.org/10.1016/j.gene.2008.02.009 | DOI Listing |
PLoS One
January 2025
Department of Biology, Swarthmore College, Swarthmore, Pennsylvania, United States of America.
Mental illnesses put a tremendous burden on afflicted individuals and society. Identification of novel drugs to treat such conditions is intrinsically challenging due to the complexity of neuropsychiatric diseases and the need for a systems-level understanding that goes beyond single molecule-target interactions. Thus far, drug discovery approaches focused on target-based in silico or in vitro high-throughput screening (HTS) have had limited success because they cannot capture pathway interactions or predict how a compound will affect the whole organism.
View Article and Find Full Text PDFPLoS One
January 2025
Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, Morocco.
Cognitive dysfunction in Alzheimer's disease results from a complex interplay of various pathological processes, including the dysregulation of key enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidase B (MAO-B). This study proposes and designs a series of novel molecules derived from 8-hydroxyquinoline (Azo-8HQ) as potential multi-target lead candidates for treating AD. An exhaustive in silico analysis was conducted, encompassing docking studies, ADMET analysis, density functional theory (DFT) studies, molecular dynamics simulations, and subsequent MM-GBSA calculations to examine the pharmacological potential of these molecules with the specific targets of interest.
View Article and Find Full Text PDFRheumatology (Oxford)
January 2025
Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangdong Laboratory, Guangzhou, 510515, China.
Objectives: The relationship between proteomic profiles and incident systemic lupus erythematosus (SLE) remains unclear. We aimed to identify candidate plasma proteins for SLE risk in women, discover potential treatment targets for SLE, and develop and validate a protein-based prediction model for SLE risk.
Methods: 28 220 women from the UK Biobank were randomly split into training (70%) and testing (30%) sets.
Mol Divers
January 2025
Integrated Drug Discovery Centre, Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru, 560107, Karnataka, India.
Discoidin domain receptors (DDR) are categorized under tyrosine kinase receptors (RTKs) and play a crucial role in various etiological conditions such as cancer, fibrosis, atherosclerosis, osteoarthritis, and inflammatory diseases. The structural domain rearrangement of DDR1 and DDR2 involved six domains of interest namely N-terminal DS, DS-like, intracellular juxtamembrane, transmembrane juxtamembrane, extracellular juxtamembrane intracellular kinase domain, and the tail portion contains small C-tail linkage. DDR has not been explored to a wide extent to be declared as a prime target for any particular pathological condition.
View Article and Find Full Text PDFInfection
January 2025
Department of Thoracic Surgery, Saarland University, 66421, Homburg/Saar, Germany.
Background: Lung transplantation is the ultimate treatment option for patients with advanced cystic fibrosis. Chronic colonization of these recipients with multidrug-resistant (MDR) pathogens may constitute a risk factor for an adverse outcome. We sought to analyze whether colonization with MDR pathogens, as outlined in the German classification of multiresistant Gram-negative bacteria (MRGN), was associated with the success of lung transplantation.
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