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Baka, Israel

Ursu O.,University of New Mexico | Rayan A.,Hebrew University of Jerusalem | Rayan A.,Qasemi Research Center | Goldblum A.,Hebrew University of Jerusalem | Oprea T.I.,University of New Mexico
Wiley Interdisciplinary Reviews: Computational Molecular Science

'Drug-likeness', a qualitative property of chemicals assigned by experts committee vote, is widely integrated into the early stages of lead and drug discovery. Its conceptual evolution paralleled work related to Pfizer's 'rule of five' and lead-likeness, and is placed within this framework. The discrimination between 'drugs' (represented by a collection of pharmaceutically relevant small molecules, some of which are marketed drugs) and 'nondrugs' (typically, chemical reagents) is possible using a wide variety of statistical tools and chemical descriptor systems. Here we summarize 18 papers focused on drug-likeness, and provide a comprehensive overview of progress in the field. Tools that estimate drug-likeness are valuable in the early stages of lead discovery, and can be used to filter out compounds with undesirable properties from screening libraries and to prioritize hits from primary screens. As the goal is, most often, to develop orally available drugs, it is also useful to optimize drug-like pharmacokinetic properties. We examine tools that evaluate drug-likeness and some of their shortcomings, challenges facing these tools, and address the following issues: What is the definition of drug-likeness and how can it be utilized to reduce attrition rate in drug discovery? How difficult is it to distinguish drugs from nondrugs? Are nondrug datasets reliable? Can we estimate oral drug-likeness? We discuss a drug-like filter and recent advances in the prediction of oral drug-likeness. The heuristic aspect of drug-likeness is also addressed. © 2011 John Wiley & Sons, Ltd. Source

Daragmeh J.,Arab American University - Jenin | Barriah W.,Qasemi Research Center | Saad B.,Arab American University - Jenin | Zaid H.,Arab American University - Jenin
Oncology Letters

Recent advances in genomics, proteomics, cell biology and biochemistry of tumors have revealed new pathways that are aberrantly activated in numerous cancer types. However, the enormous amount of data available in this field may mislead scientists in focused research. As cancer cell growth and progression is often dependent upon the phosphoinositide 3-kinase (PI3K)/AKT pathway, there has been extensive research into the proteins implicated in the PI3K pathway. Using data available in the Human Protein Atlas database, the current study investigated the expression of 25 key proteins that are known to be involved with PI3K pathway activation in a distinct group of 20 cancer types. These proteins are AKTIP, ARP1, BAD, GSK3A, GSK3B, MERTK-1, PIK3CA, PRR5, PSTPIP2, PTEN, FOX1, RHEB, RPS6KB1, TSC1, TP53, BCL2, CCND1, WFIKKN2, CREBBP, caspase-9, PTK2, EGFR, FAS, CDKN1A and XIAP. The analysis revealed pronounced expression of specific proteins in distinct cancer tissues, which may have the potential to serve as targets for treatments and provide insights into the molecular basis of cancer. © 2016, Spandidos Publications. All rights reserved. Source

Saad B.,Regional Development Centre | Saad B.,Qasemi Research Center | Saad B.,Arab American University - Jenin | Abouatta B.S.,Regional Development Centre | And 5 more authors.
Evidence-based Complementary and Alternative Medicine

Based on knowledge from traditional Arab herbal medicine, this in vitro study aims to examine the anti-inflammatory mechanism of Hypericum triquetrifolium by measuring the expression and release of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6), and inducible nitric oxide synthase (iNOS) in human monocytic cells, THP-1. The effects were assessed by measuring the levels of secretory proteins and mRNA of TNF-α and IL-6, the levels of nitric oxide (NO) secretion and the expression of iNOS in THP-1 cells. Cells were treated with 5g lipopolysaccharide/ml (LPS) in the presence and absence of increasing concentrations of extracts from the aerial parts of H. triquetrifolium. During the entire experimental period, we used extract concentrations (up to 250μgmL-1) that had no cytotoxic effects, as measured with MTT and LDH assays. Hypericum triquetrifolium extracts remarkably suppressed the LPS-induced NO release, significantly attenuated the LPS-induced transcription of iNOS and inhibited in a dose-dependent manner the expression and release of TNF-α. No significant effects were observed on the release of IL-6. Taken together, these results suggest that H. triquetrifolium probably exerts anti-inflammatory effects through the suppression of TNF-α and iNOS expressions. Copyright © 2011 Bashar Saad et al. Source

Shahaf N.,Qasemi Research Center | Pappalardo M.,University of Catania | Rayan A.,Qasemi Research Center | Rayan A.,AMR Research
Molecular Informatics

G protein-coupled receptors (GPCRs) are a super-family of membrane proteins that attract great pharmaceutical interest due to their involvement in almost every physiological activity, including extracellular stimuli, neurotransmission, and hormone regulation. Currently, structural information on many GPCRs is mainly obtained by the techniques of computer modelling in general and by homology modelling in particular. Based on a quantitative analysis of eighteen antagonist-bound, resolved structures of rhodopsin family "A" receptors - also used as templates to build 153 homology models - it was concluded that a higher sequence identity between two receptors does not guarantee a lower RMSD between their structures, especially when their pair-wise sequence identity (within trans-membrane domain and/or in binding pocket) lies between 25% and 40%. This study suggests that we should consider all template receptors having a sequence identity ≤50% with the query receptor. In fact, most of the GPCRs, compared to the currently available resolved structures of GPCRs, fall within this range and lack a correlation between structure and sequence. When testing suitability for structure-based drug design, it was found that choosing as a template the most similar resolved protein, based on sequence resemblance only, led to unsound results in many cases. Molecular docking analyses were carried out, and enrichment factors as well as attrition rates were utilized as criteria for assessing suitability for structure-based drug design. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Azaizeh H.,Galilee Society R and nter | Azaizeh H.,Qasemi Research Center | Saad B.,Galilee Society R and nter | Saad B.,Qasemi Research Center | And 4 more authors.
Evidence-based Complementary and Alternative Medicine

Complementary medicine is a formal method of health care in most countries of the ancient world. It is expected to become more widely integrated into the modern medical system, including the medical curriculum. Despite the perception of modern medicine as more efficacious, traditional medicine continues to be practiced. More than 70 of the developing worlds population still depends primarily on the complementary and alternative systems of medicine (CAM). In rural areas, cultural beliefs and practices often lead to self-care, home remedies or consultation with traditional healers. Herbal medicine can be broadly classified into four basic systems as follows: Traditional Chinese Herbalism, Ayurvedic Herbalism, Western Herbalismwhich originally came from Greece and Rome to Europe and then spread to North and South America and Traditional Arabic and Islamic Medicine (TAIM). There is no doubt that today the concept of Arabic traditional herbal medicine is a part of modern life in the Middle East, and it is acquiring worldwide respect, with growing interest among traditional herbalists and the scientific community. TAIM therapies have shown remarkable success in healing acute as well as chronic diseases and have been utilized by people in most countries of the Mediterranean who have faith in spiritual healers. TAIM is the first choice for many in dealing with ailments such as infertility, epilepsy, psychosomatic troubles and depression. In parallel, issues of efficacy and safety of complementary medicine have become increasingly important and supervision of the techniques and procedures used is required for commercial as well as traditional uses. More research is therefore needed to understand this type of medicine and ensure its safe usage. The present review will discuss the status of traditional Arab medicine (particularly herbal medicine), including the efficacy and toxicity of specific medicinal preparations, with an emphasis on the modern in vitro and in vivo techniques. © 2008 The Author(s). Source

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