Abstract：
:The disruption of large protein-protein (PP) interfaces remains a challenge in targeted therapy. Designing drugs that compete with binding partners is daunting, especially when the structure of the protein complex is unknown. To address the problem we propose a deep protein databank (PDB) learning platform to discover targetable epitopes for complex-disruptive leads.
journal_name
Trends Pharmacol Scijournal_title
Trends in pharmacological sciencesauthors
Fernández Adoi
10.1016/j.tips.2019.04.009subject
Has Abstractpub_date
2019-08-01 00:00:00pages
551-554issue
8eissn
0165-6147issn
1873-3735pii
S0165-6147(19)30086-0journal_volume
40pub_type
杂志文章abstract：:Progress in understanding the genetic changes that drive tumorigenesis has enabled the development of molecularly targeted anticancer therapy. The first small molecule targeted to a specific protein was imatinib mesylate (Gleevec, STI571), which is used to treat chronic myeloid leukemia (CML). A recent article present...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2007.03.003
更新日期：2007-05-01 00:00:00
abstract：:Multidrug resistance is associated with the overexpression of P-glycoprotein, a membrane glycoprotein. The mechanism by which P-glycoprotein confers to cells the capacity to resist cytotoxic attack by structurally unrelated drugs has remained difficult to decipher. However, the recent functional expression of this gro...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(94)90322-0
更新日期：1994-07-01 00:00:00
abstract：:Kinin B1 and B2 receptors are central to the aetiology of pain and inflammation. Constitutive B2 receptors are commonly associated with the acute phase of inflammation and nociception, whereas the inducible B1 receptors are mostly linked to the chronic or persistent phase (or both). Therefore, selective, orally active...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.10.007
更新日期：2006-12-01 00:00:00
abstract：:There is increasing awareness of the compartmentalization of cAMP signalling--the means by which cAMP levels change in discrete domains of the cell with discrete local consequences. Current developments in understanding the organization of adenylyl cyclases in the plasma membrane are illuminating how the earliest part...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.06.002
更新日期：2006-08-01 00:00:00
abstract：:Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in developed nations. Therapeutic modulation of dyslipidemia by inhibiting 3'-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is standard practice throughout the world. However, based on findings from Mendelian ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2018.06.001
更新日期：2018-08-01 00:00:00
abstract：:Neuronal Ca2+-sensor (NCS) proteins constitute a subfamily of closely related EF-hand Ca2+-binding proteins that are expressed mainly in neurons or retinal photoreceptor cells. A variety of different neuronal functions have been attributed to these proteins. However, important new discoveries indicate that these prote...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.04.008
更新日期：2005-07-01 00:00:00
abstract：:Lithium is the simplest therapeutic agent available for the treatment of depression and has been used for over 100 years, yet no definitive mechanism for its effect has been established. Among the proposed mechanisms, two lithium-sensitive signal transduction pathways are active in the brain; these are mediated by gly...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/s0165-6147(99)01428-5
更新日期：2000-02-01 00:00:00
abstract：:In the discipline of pharmacology, drugs (ligands) are used as tools to elucidate the processes of biological systems. Because of this, pharmacologists strive to delineate all characteristics of drugs. Decades of research have resulted in the proposal that ligands possess two properties that are intrinsic to the ligan...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01138-3
更新日期：1998-07-01 00:00:00
abstract：:Since conformational flexibility, which is required for the function of a protein, comes at the expense of structural stability, many proteins, including G-protein-coupled receptors (GPCRs), are under constant risk of misfolding and aggregation. In this regard GPR37 (also named PAEL-R and ETBR-LP-1) takes a prominent ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2017.05.006
更新日期：2017-08-01 00:00:00
abstract：:Recruitment of leukocytes either during development or to the site of injury is crucial. The molecular regulation of cell trafficking is complex but well orchestrated by the temporal and spatial expression of a multitude of chemokines (chemoattractant cytokines) and chemokine receptors. The chemokines, classified prim...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01342-5
更新日期：1999-04-01 00:00:00
abstract：:Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight emerging novel and easil...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.10.014
更新日期：2017-02-01 00:00:00
abstract：:Advances in the understanding of the sense of smell have increased awareness of the role of olfaction in human life. Odors are perceived via specific G protein-coupled receptors (GPCRs) with cAMP as the second messenger. Drugs that interact with this signaling cascade, such as opioids, cannabinoids and sildenafil, are...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2012.01.004
更新日期：2012-04-01 00:00:00
abstract：:In the conventional view, GABA acts at either ionotropic GABAA or metabotropic GABAB receptors. Recently, novel ionotropic GABA receptors that are composed of rho-subunits have been identified in the vertebrate retina. These bicuculline- and baclofen-insensitive GABA receptors are frequently called GABAC, following an...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(99)01413-3
更新日期：2000-01-01 00:00:00
abstract：:Biogenic amines and amino acids have been implicated in central cardiovascular homeostasis. Initially, drugs were injected into the brain and their effects on blood pressure were investigated. Other approaches allowed endogenous neurotransmitters released in the extracellular space of brain structures involved in card...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：
更新日期：1996-10-01 00:00:00
abstract：:Opioid receptors are expressed on peripheral sensory nerve endings, cutaneous cells, and immune cells; and local application of opioids is used for the treatment of inflammatory pain in arthritis, burns, skin grafts, and chronic wounds. However, peripherally active opioids can also directly modulate the inflammatory p...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2013.03.006
更新日期：2013-06-01 00:00:00
abstract：:The physiological roles of chemokine receptors have expanded beyond host defense and now represent important targets for intervention in several disease indications. Chemokine receptors have joined the ranks of other members of the G-protein-coupled receptor (GPCR) family in therapeutic potential as small-molecule che...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(02)02064-3
更新日期：2002-10-01 00:00:00
abstract：:New classes of drugs modifying Ca2+ channel activity have become available, this may enlarge the clinical utilities that have been associated with established Ca2+ channel antagonists such as the dihydropyridines (for example, nifedipine). Two such classes are reviewed by Michael Spedding, Barry Kenny and Pierre Chate...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(00)89002-1
更新日期：1995-04-01 00:00:00
abstract：:Elucidating plant-specialized biosynthetic pathways has always constituted a laborious task, notably for natural products with high pharmaceutical values. Here, we discuss emerging omics-based strategies that facilitate the identification of genes from these complex metabolic pathways, paving the way to engineered sup...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2019.12.006
更新日期：2020-03-01 00:00:00
abstract：:Thiol-based drugs are considered as mucolytics because they decrease the viscosity and mostly decrease the elasticity of bronchial secretions by reducing disulfide bonds in proteins. However, they can also act as antioxidant drugs directly through free sulfhydryl groups that serve as a source of reducing equivalents, ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.tips.2019.04.015
更新日期：2019-07-01 00:00:00
abstract：:Ca2+ channels in the plasma membrane of T cells vitally influence Ca2+-dependent signals that lead ultimately to cytokine secretion, cellular proliferation and apoptosis. Conventional models depict the Ca2+ inrush across the T-cell membrane following T-cell receptor engagement as being due to Ca2+-release-activated Ca...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2006.05.007
更新日期：2006-07-01 00:00:00
abstract：:Sulfoconjugation of drugs and small xenobiotic and endogenous compounds in human tissues is primarily catalysed by cytosolic forms of sulfotransferase. In most instances, sulfate conjugation is associated with a decrease in the biological activity and an increase in the excretion of the sulfated compounds. However, su...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/0165-6147(91)90566-b
更新日期：1991-07-01 00:00:00
abstract：:Degradation of heme requires its conversion to biliverdin (BV) by heme oxygenase, followed by reduction of BV to the free-radical quencher bilirubin (BR) by biliverdin reductase (BVR). It is now recognized that human BVR (hBVR) is a dual-specificity kinase (Ser/Thr and Tyr) upstream activator of the insulin/insulin gr...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2008.12.003
更新日期：2009-03-01 00:00:00
abstract：:Intercellular transfer of proteins is a mode of communication between cells that is crucial for certain physiological processes. Chemotherapy is the treatment of choice for approximately 50% of all cancers. However, multidrug resistance mediated by drug-efflux pumps such as P-glycoprotein (Pgp) minimizes the effective...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2005.06.001
更新日期：2005-08-01 00:00:00
abstract：:Pharmacology as a modern science was introduced in China approximately 150 years ago, and has been used since then to study traditional Chinese medicine (TCM). Pharmacology has experienced its own development over this time and continues to provide new tools for the study of TCM. In the present review, three models fo...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2013.09.004
更新日期：2013-11-01 00:00:00
abstract：:Changes in the structure and function of the small airways (<2mm diameter) are now recognized to play a major role in airflow limitation in both chronic obstructive pulmonary disease (COPD) and severe asthma. Increased thickness of the small airway wall causes lumenal narrowing, which can be further occluded by mucus ...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2008.04.003
更新日期：2008-07-01 00:00:00
abstract：:Upregulation of binding to nicotinic acetylcholine receptors (nAChRs) is observed in the brains of both smokers and animals chronically exposed to nicotine, although whether this in vivo change is accompanied by an increase in receptor function is unknown. In vitro recordings indicate that alpha4beta2- and alpha7-subt...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/S0165-6147(00)01979-9
更新日期：2002-03-01 00:00:00
abstract：:Release of cytotoxic granule proteins from activated eosinophil granules is considered to be a key pathogenic mechanism in eosinophilic diseases. Degenerated eosinophils and extracellular eosinophil granules have been repeatedly depicted. The present overview describes evidence that eosinophil lysis and distribution o...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/s0165-6147(97)01042-0
更新日期：1997-04-01 00:00:00
abstract：:The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of immunomodulatory receptors whose functions are regulated by their glycan ligands. Siglecs are attractive therapeutic targets because of their cell type-specific expression pattern, endocytic properties, high expression on certain lymphomas/l...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2015.06.008
更新日期：2015-10-01 00:00:00
abstract：:During the past decade, translocator protein 18 kDa (TSPO), previously named peripheral benzodiazepine receptor, has gained a great deal of attention based on its use as a clinical biomarker of neuroinflammation with therapeutic potential. However, there is a paucity of knowledge on the function(s) of TSPO in glial ce...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2016.02.008
更新日期：2016-05-01 00:00:00
abstract：:Alanine-glyoxylate aminotransferase 2 (AGXT2) is a multifunctional mitochondrial aminotransferase that was first identified in 1978. The physiological importance of AGXT2 was largely overlooked for three decades because AGXT2 is less active in glyoxylate metabolism than AGXT1, the enzyme that is deficient in primary h...
journal_title：Trends in pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1016/j.tips.2014.09.005
更新日期：2014-11-01 00:00:00
