Abstract:
:Drug designing targeting protein-protein interactions is challenging. Because structural elucidation and computational analysis have revealed the importance of hot spot residues in stabilizing these interactions, there have been on-going efforts to develop drugs which bind the hot spots and out-compete the native protein partners. The question arises as to what are the key 'druggable' properties of hot spots in protein-protein interactions and whether these mimic the general hot spot definition. Identification of orthosteric (at the protein- protein interaction site) and allosteric (elsewhere) druggable hot spots is expected to help in discovering compounds that can more effectively modulate protein-protein interactions. For example, are there any other significant features beyond their location in pockets in the interface? The interactions of protein-protein hot spots are coupled with conformational dynamics of protein complexes. Currently increasing efforts focus on the allosteric drug discovery. Allosteric drugs bind away from the native binding site and can modulate the native interactions. We propose that identification of allosteric hot spots could similarly help in more effective allosteric drug discovery. While detection of allosteric hot spots is challenging, targeting drugs to these residues has the potential of greatly increasing the hot spot and protein druggability.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Ma B,Nussinov Rdoi
10.2174/13816128113199990073subject
Has Abstractpub_date
2014-01-01 00:00:00pages
1293-301issue
8eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20130522-11journal_volume
20pub_type
杂志文章,评审abstract:BACKGROUND:Sulfur mustard (SM)-induced airway injuries and chronic obstructive pulmonary disease (COPD) are characterized by chronic inflammation of the respiratory tract and share some similarities regarding the cellular and molecular mechanisms orchestrating airway destruction. Since available data regarding the immu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160307150818
更新日期:2016-01-01 00:00:00
abstract::This article reviews evidence that hyperpolarization-activated, cation nonselective (HCN) channels, the molecular basis of the Ih current, potentially represent valid targets for novel analgesic agents. Ih is a prominent current in many peripheral sensory nerves, with highest current density typically found in large d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788489122
更新日期:2009-01-01 00:00:00
abstract::Periodontal disease is chronic inflammation of periodontal tissues resulting in formation of periodontal pockets, periodontal attachment loss and progressive destruction of the ligament and alveolar bone. This review gives an update on periodontal disease pathogenesis, which is important for the development of novel m...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150531171829
更新日期:2015-01-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel member of the secretin/glucagon/vasoactive intestinal peptide (VIP) superfamily. In vertebrates, including avians, it occurs in two forms: PACAP(38) and PACAP(27). PACAP structure is well conserved during evolution, being identical in mammals, and s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033391586
更新日期:2003-01-01 00:00:00
abstract::Mediation of antinociception via opioid receptors located in the periphery is a viable strategy to produce analgesia without the occurrence of side effects associated with stimulation of opioid receptors located in the central nervous system. Peripheral opioid receptors are particularly important in inflammatory pain ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043453036
更新日期:2004-01-01 00:00:00
abstract::Management of hypertension has evolved steadily through 25 years of major clinical trials results modifying both the definition of hypertension and clinical management strategies. Trials experience in heart failure is much less extensive given the far smaller therapeutic market and traditionally often followed on the ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454504
更新日期:2003-01-01 00:00:00
abstract::Patients with diabetes mellitus (DM) type 2 have a high prevalence of coronary artery disease (CAD), as diabetes is implicated in the formation of atherosclerotic plaque. Hyperglycemia, elevated free fatty acid, increased amount of circulating end-glucosylated serum products and insulin resistance are the main mechani...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788453185
更新日期:2009-01-01 00:00:00
abstract::Arrhythmias in left ventricular hypertrabeculation/noncompaction (LVHT) comprise sustained or non-sustained ventricular tachycardia (VT) (n=135), atrial fibrillation (AF) (n=96) AV block (n=55) and QT prolongation (n=47). The prevalence differs between children and adults. In children most frequent are WPW-syndrome (n...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793176518
更新日期:2010-01-01 00:00:00
abstract::The rapid advancement of computer architectures and development of mathematical algorithms offer a unique opportunity to leverage the simulation of macromolecular systems at physiologically relevant timescales. Herein, we discuss the impact of diverse structure-based and ligand-based molecular modeling techniques in d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190304123545
更新日期:2019-01-01 00:00:00
abstract::Over the past decade, Lymphocyte Function-Associated Antigen-1 (LFA-1, alphaLbeta2, CD11a/CD18) has emerged as an attractive therapeutic target for the treatment of multiple inflammatory diseases. Its established role in the trafficking and activation of leukocytes coupled with the recent elucidation of the global con...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206777947731
更新日期:2006-01-01 00:00:00
abstract::Over the last years a number of reports have described elevated numbers of regulatory T (Treg) cells inside of tumors, in close proximity of the tumor, draining lymph nodes and also in peripheral blood of patients with solid tumors and hematologic malignancies. There is increasing evidence that Treg cells can migrate ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788453211
更新日期:2009-01-01 00:00:00
abstract::Stability of a dosage form is its ability to preserve its quality attributes within preset limits. The time span over which these attributes remain within specifications is the shelf-life of the drug product. Stability is a very complex feature and is influenced not only by the stability of the drug substance but also...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160726094236
更新日期:2016-01-01 00:00:00
abstract::These are exciting times for bioinformaticians, computational biologists and drug designers with the genome and proteome sequences and related structural databases growing at an accelerated pace. The post-genomic era has triggered high expectations for a rapid and successful treatment of diseases. However, in this bio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990379
更新日期:2013-01-01 00:00:00
abstract::Heat shock proteins (HSPs) are involved in a number of cellular processes, including cell cycle, growth, and survival, apoptosis, stress responses, angiogenesis, and oncogenesis. Among the characterized HSPs, the molecular chaperone HSP90 has emerged as an exciting molecular target for cancer therapy since its discove...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::microRNAs (miRNAs) comprise a recently discovered class of non-coding RNAs with regulatory functions in post-transcriptional gene expression control. Many miRNAs are located in genomic regions that are frequently deleted in cancer, or are subject to epigenetic and transcriptional deregulation in cancer cells. The miRN...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161213804805649
更新日期:2013-01-01 00:00:00
abstract::There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitam...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190709220449
更新日期:2019-01-01 00:00:00
abstract::There is a plausible role for cytokines, brain-derived neurotrophic factor (BDNF), and their interaction in major depressive disorder's (MDD) etiology. This review includes (i) briefly defining cytokines, (ii) a discussion of theories for why they may affect brain function, (iii) cross-sectional associations between c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803523680
更新日期:2012-01-01 00:00:00
abstract::Interest in opioid drugs like morphine, as the oldest and most potent pain-killing agents known, has been maintained through the years. One of the most frequent chronic pain sensations people experience is associated with pathological conditions of the musculoskeletal system. Chronic musculoskeletal pain is a major he...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990363
更新日期:2013-01-01 00:00:00
abstract::The treatment of skin wounds represents an important research area due to the important physiological and aesthetic role of this tissue. During the last years, nanoparticles have emerged as important platforms to treat skin wounds. Silver, gold, and copper nanoparticles, as well as titanium and zinc oxide nanoparticle...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150901104601
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Pulmonary diseases are the third leading cause of morbidity worldwide, however treatment and diagnosis of these diseases continue to be challenging due to the complex anatomical structure as well as physiological processes in the lungs. METHODS:3D printing is progressively finding new avenues in the medical...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666181206123414
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Absorption windows in particular segments of the small intestine can contribute to the development of orally administered drug formulations and can limit the bioavailability of released compounds. OBJECTIVE:The aim of this study was to evaluate use of wireless capsule enteroscopy regarding the disintegratio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612822666161201145247
更新日期:2017-01-01 00:00:00
abstract::Donkey's milk is the best substitute of human milk for its content in lactose, proteins, minerals, and omega-3 fatty acids. Here, we have evaluated the effects of colostrum and milk from donkeys (Martina Franca breed) on the function of human peripheral blood mononuclear cells (PBMCs) at different intervals from lacta...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161207783018590
更新日期:2007-01-01 00:00:00
abstract::Many, if not all, chronic medical, neurodegenerative and neuroprogressive illnesses are characterised by chronic immune activation, oxidative and nitrosative stress (O&NS) and systemic inflammation. These factors, notably elevated pro-inflammatory cytokines, activate indoleamine 2,3-dioxygenase (IDO) leading to an upr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151215102420
更新日期:2016-01-01 00:00:00
abstract::Deubiquitinating enzymes (DUBs) remove ubiquitin and ubiquitin-like modifications from proteins and they have been known to contribute to processes relevant in microbial infection, such as immune responses pathways. Numerous viral and bacterial DUBs have been identified, and activities of several host DUBs are known t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319180008
更新日期:2013-01-01 00:00:00
abstract::Nuclear medicine offers powerful noninvasive techniques for visualization of infectious and inflammatory disorders using whole body imaging enabling the determination of both localization and number of inflammatory foci. A wide variety of approaches depicting the different stages of the inflammatory response have been...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043383539
更新日期:2004-01-01 00:00:00
abstract::The Hereditary Spastic Paraparesis (HSP) or Strumpell-Lorrain disease is a heterogeneous neurodegenerative disease of the spinal cord. It is genetically transmitted and characterized by a progressive muscle weakness, spasticity of the lower limbs and awkward gain. There is no specific pharmacological treatment. The ph...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612822666151204001830
更新日期:2016-01-01 00:00:00
abstract::The frequency of neuropsychiatric disorders is greater than that of cancer, cardiovascular disease, and diabetes combined, and is growing at a faster rate than any other ailments in the United States or Europe. Despite a considerable need for the development of treatments for central nervous system disorders, pharmace...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160127111453
更新日期:2016-01-01 00:00:00
abstract::Synaptic transmission through descending motor pathways to lumbar motoneurons and then to leg muscles is essential for walking in humans and rats. Spinal cord injury (SCI), even when incomplete, results in diminished transmission to motoneurons and very limited recovery of motor function. Neurotrophins have emerged as...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990378
更新日期:2013-01-01 00:00:00
abstract::We conducted a systematic review on resting state cerebral blood flow activities found in first-episode psychosis (FEP) and during acute effects of cannabinoids and opioids, mental states that can be profoundly different from normal functioning. The main goal was to identify connections of cerebral blood flow measure ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212802884717
更新日期:2012-01-01 00:00:00
abstract::Although escape from tumor dormancy has long been recognized as an important problem in the treatment of cancer, the molecular and cellular regulators underlying this transition remain poorly understood. The inability of the cancer cells to induce a complete and successful process of angiogenesis can result in tumor d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612819666131125153536
更新日期:2014-01-01 00:00:00