Abstract:
:Drug-induced rhabdomyolysis (DIR) is an idiosyncratic and fatal adverse drug reaction (ADR) characterized in severe muscle injuries accompanied by multiple-organ failure. Limited knowledge regarding the pathophysiology of rhabdomyolysis is the main obstacle to developing early biomarkers and prevention strategies. Given the lack of a centralized data resource to curate, organize, and standardize widespread DIR information, here we present a Drug-Induced Rhabdomyolysis Atlas (DIRA) that provides DIR-related information, including: a classification scheme for DIR based on drug labeling information; postmarketing surveillance data of DIR; and DIR drug property information. To elucidate the utility of DIRA, we used precision dosing, concomitant use of DIR drugs, and predictive modeling development to exemplify strategies for idiosyncratic ADR (IADR) management.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Wen Z,Liang Y,Hao Y,Delavan B,Huang R,Mikailov M,Tong W,Li M,Liu Zdoi
10.1016/j.drudis.2018.06.006subject
Has Abstractpub_date
2019-01-01 00:00:00pages
9-15issue
1eissn
1359-6446issn
1878-5832pii
S1359-6446(17)30585-8journal_volume
24pub_type
杂志文章,评审abstract::The intestinal epithelium is the main barrier restricting the oral delivery of low-permeability drugs. Over recent years, numerous nanocarriers have been designed to improve the efficiency of oral drug delivery. However, the intracellular processes determining the transport of nanocarriers across the intestinal epithe...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.04.007
更新日期:2016-05-01 00:00:00
abstract::During the past 10 years, substantial progress has been made in the discovery and development of small molecule glutamate carboxypeptidase II (GCP II) inhibitors. These inhibitors have provided the necessary tools to investigate the physiological role of GCP II as well as the potential therapeutic benefits of its inhi...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.07.010
更新日期:2007-09-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a progressive disease that involves pathological remodeling, vasoconstriction and thrombosis. Alterations in hemostasis, coagulation and platelet activation are consistently observed in PAH patients. Microparticles derived from platelets, inflammatory cells and the endothelium ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.04.001
更新日期:2014-08-01 00:00:00
abstract::Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potenti...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.01.012
更新日期:2014-06-01 00:00:00
abstract::Drug discovery and development is a highly complex process requiring the generation of very large amounts of data and information. Currently this is a largely unmet informatics challenge. The current approaches to building information and knowledge from large amounts of data has been addressed in cases where the types...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(02)02433-9
更新日期:2002-09-15 00:00:00
abstract::It is widely accepted that placental ischemia is central in the evolution of hypertension in pregnancy. Many studies and reviews have targeted placental ischemia to explain mechanisms for initiating pregnancy hypertension. The placenta is rich in blood vessels, which are the basis for developing placental ischemia. Ho...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.10.021
更新日期:2018-02-01 00:00:00
abstract::For a fortunate subset of pharmaceutical companies, a regulatory approval is the culmination of massive investment in time, work and money. What happens next? Some companies proceed to build a pipeline and obtain additional approvals. Others do not. In this present report, post-approval fate is evaluated and it was fo...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2014.10.013
更新日期:2015-02-01 00:00:00
abstract::Novel starting points for drug discovery projects are generally found either by screening large collections of compounds or smaller more-focused libraries. Ideally, hundreds or even thousands of actives are initially found, and these need to be reduced to a handful of promising lead series. In several sequential steps...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03703-7
更新日期:2006-01-01 00:00:00
abstract::Drug discovery has historically advanced by synergy and chance. These are proving insufficient to meet the needs of the marketplace and the demands of modern medicine. We describe our strategic approaches to building and employing flexible informatics tools to transform and improve the workflows and efficiencies of th...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03277-5
更新日期:2005-01-01 00:00:00
abstract::The Science for Life Laboratory Drug Discovery and Development (SciLifeLab DDD) platform reaches out to Swedish academia with an industry-standard infrastructure for academic drug discovery, supported by earmarked funds from the Swedish government. In this review, we describe the build-up and operation of the platform...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.06.026
更新日期:2016-10-01 00:00:00
abstract::The nuclear receptors constitutive androstane receptor (CAR), pregnane X receptor (PXR) and vitamin D receptor (VDR) control a large array of genes that code for important proteins in humans including metabolic enzymes and transporters. 3D structures for the ligand-binding domain (LBD) of these receptors are abundantl...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.01.001
更新日期:2013-06-01 00:00:00
abstract::This review provides an update on the promises and pitfalls when using in vitro bioassays to evaluate beneficial and adverse health effects of botanicals and botanical preparations. Important issues addressed in the paper are: (i) the type of assays and biological effects available; (ii) false-positives, false-negativ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.05.002
更新日期:2017-08-01 00:00:00
abstract::Recent groundbreaking work in genetics has identified thousands of small-effect genetic variants throughout the genome that are associated with almost all major diseases. These genome-wide association studies (GWAS) are often proposed as a source of future medical breakthroughs. However, with several notable exception...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2015.05.012
更新日期:2015-10-01 00:00:00
abstract::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01619-6
更新日期:2001-02-01 00:00:00
abstract::Following the introduction of antibiotic therapy and widespread inoculations, cardiovascular diseases have leapt ahead of infectious diseases in terms of prevalence in much of the developed and developing world. Herein, we assess FDA-approved drugs for the treatment of cardiovascular diseases. The drug development ent...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2014.09.001
更新日期:2016-01-01 00:00:00
abstract::Kidneys have a major role in normal physiology and metabolic homeostasis. Loss or impairment of kidney function is a common occurrence in several metabolic disorders, including hypertension and diabetes. Chronic kidney disease (CKD) affect nearly 10% of the population worldwide; ranks 18th in the list of causes of dea...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.04.020
更新日期:2017-07-01 00:00:00
abstract::Analyzers for in-vitro diagnostic (IVD) testing facilitate the determination of medical information from biological samples. To reach a high quality, the detection reagents have to be dispensed with a high degree of precision and accuracy. A technology change from conventional pipetting systems to contact-free dispens...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2013.06.011
更新日期:2013-11-01 00:00:00
abstract::RNA interference (RNAi) and small-molecule approaches are synergistic on multiple levels, from technology and high-throughput screen development to target identification and functional studies. Here, we describe the RNAi screening platform that we have established and made available to the community through the Drosop...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2006.10.006
更新日期:2007-01-01 00:00:00
abstract::Micro RNAs (miRNAs) are a class of naturally occurring ∼ 22 nt long non-coding small RNA molecules that regulate the expression of a wide range of genes involved in development, growth, proliferation and apoptosis. miRNAs are evolutionarily conserved from plants to animals, and they regulate and fine-tune a diverse ar...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2010.07.003
更新日期:2010-09-01 00:00:00
abstract::Huntington's disease (HD) is a progressive and fatal neurodegenerative disease, and the most common inherited CAG repeat disorder. A polyglutamine expansion in the N-terminus of the huntingtin protein (HTT) leads to protein misfolding and downstream pathogenic processes culminating in widespread functional impairment ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.06.017
更新日期:2012-11-01 00:00:00
abstract::This memorandum is addressed to members of regulatory agencies, as well as managers of pharmaceutical companies. Pharmacokineticists and toxicologists may consider this proposal, weigh its merits, and provide input for implementation. Experience from academic research and ADME experiments during drug development has p...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.06.006
更新日期:2007-08-01 00:00:00
abstract::The completion of the human genome sequencing project has provided a flood of new information that is likely to change the way scientists approach the study of complex biological systems. A major challenge lies in translating this information into new and better ways to treat human disease. The multidisciplinary scien...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:
更新日期:2004-01-15 00:00:00
abstract::Identifying the right target for drug development is a critical bottleneck in the pharmaceutical and biotech industries. The genomics revolution has shifted the problem from a scarcity of targets to a surplus of putative drug targets. As the validity of a target cannot be simply inferred from correlative data, the key...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(02)02429-7
更新日期:2002-09-15 00:00:00
abstract::In the past five years therapeutic monoclonal antibodies have established themselves as perhaps the most important and rapidly expanding class of therapeutic drugs. More than 25% of pharmacological agents that are currently under development are based on antibodies and the total income generated from them in 2002 exce...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(03)02714-4
更新日期:2003-06-01 00:00:00
abstract::The function of many key proteins and transcription factors involved in cell growth can be regulated by their cellular localization. Such proteins include the tumor suppressor p53 and the nuclear factor kappaB. Although the idea of trapping such proteins in either the nucleus or cytoplasm has been introduced as a pote...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(02)02562-x
更新日期:2003-01-15 00:00:00
abstract::The increasing incidence of cutaneous malignancies signifies the need for multiple treatment options. Several available reviews have emphasized the potential role of various botanical extracts and naturally occurring compounds as anti-skin-cancer agents. Few studies relate to the role of chemoprevention and therapeuti...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.11.020
更新日期:2019-02-01 00:00:00
abstract::Since the Life Science Identifier (LSID) data identification and access standard made its official debut in late 2004, several organizations have begun to use LSIDs to simplify the methods used to uniquely name, reference and retrieve distributed data objects and concepts. In this review, the authors build on introduc...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03651-2
更新日期:2005-11-15 00:00:00
abstract::Sudden cardiac death, secondary to ventricular fibrillation (VF), remains the leading cause of death in the USA. Recent experimental and theoretical studies suggest that VF could be caused by spiral wave re-entry. The initiation and subsequent break-up of spiral waves has been linked to electrical alternans, a phenome...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(02)02567-9
更新日期:2003-02-15 00:00:00
abstract::Cocaine is a major drug of abuse whose devastating effects have captured the attention of health officials and policy makers. Based upon the alarming health and crime-related costs associated with the use of this powerful reinforcing drug, immediate therapies are needed for the treatment of cocaine addiction. In this ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(99)01332-x
更新日期:1999-07-01 00:00:00
abstract::Pharmacological modulation of intracellular cyclic AMP (cAMP) signalling could provide new therapeutic and experimental tools. Although drugs interfering with this pathway have traditionally targeted membrane receptors, the effector enzyme adenylyl cyclase (AC), which functions as a signalling catalyst, also presents ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.07.007
更新日期:2009-10-01 00:00:00