Abstract：
:The p53 family proteins are among the most appealing targets for cancer therapy. A deeper understanding of the complex interplay that these proteins establish with murine double minute (MDM)2, MDMX, and mutant p53 could reveal new exciting therapeutic opportunities in cancer treatment. Here, we summarize the most relevant advances in the biology of p53 family protein-protein interactions (PPIs), and the latest pharmacological developments achieved from targeting these interactions. We also highlight the remarkable contributions of yeast-based assays to this research. Collectively, we emphasize promising strategies, based on the inhibition of p53 family PPIs, which have expedited anticancer drug development.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Gomes S,Leão M,Raimundo L,Ramos H,Soares J,Saraiva Ldoi
10.1016/j.drudis.2016.02.007subject
Has Abstractpub_date
2016-04-01 00:00:00pages
616-24issue
4eissn
1359-6446issn
1878-5832pii
S1359-6446(16)30033-2journal_volume
21pub_type
杂志文章,评审abstract：:Increasing evidence indicates that extracellular vesicles (EVs) are key players in undesirable cell-cell communication in cancer. However, the release of EVs is not unique to cancer cells; normal cells release EVs to perform physiological roles. Thus, selective inhibition of EV release from cancer cells is desirable. ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.03.006
更新日期：2018-06-01 00:00:00
abstract：:Benford's law states that the distribution of the first digit of many data sets is not uniform. The first digit of any random number will be 1 almost 30% of the time, and larger digits occur as the first digit with lower and lower frequency, to the point where 9 occurs as a first digit only 5% of the time. Here, we de...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2010.03.003
更新日期：2010-05-01 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：:The excessive release of glutamate following brain injury is responsible for the phenomenon of glutamate excitotoxicity, mediated through glutamate receptors, resulting in apoptotic cell death. KDI ameliorates excitotoxicity and regenerates damaged nerve cells. ...
journal_title：Drug discovery today
pub_type： 新闻
doi：10.1016/S1359-6446(05)03617-2
更新日期：2005-10-01 00:00:00
abstract：:Idiopathic pulmonary fibrosis (IPF) is a progressive and almost invariably lethal disease that affects primarily older adults. After a decade of negative (or inconsistent) results, two recent clinical trials have demonstrated that slowing disease progression with medication is possible. An improved understanding of di...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.01.001
更新日期：2015-05-01 00:00:00
abstract：:Wnt/β-catenin signaling is an evolutionarily conserved signaling cascade with imperative roles during development and in adult stem cell maintenance. Hyperactivation of Wnt/β-catenin drives various cancers, whereas hypoactivation underlies bone malformations and neurodegenerative disorders. Although several small mole...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2010.11.007
更新日期：2011-01-01 00:00:00
abstract：:In drug discovery and development (DDD), the efficacy, safety and cost of new chemical entities are the main concerns of the pharmaceutical industry. Continuously updated and stricter recommendations imposed by regulatory authorities result in greater challenges being faced by the industry. Reliable high-throughput te...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.11.001
更新日期：2014-05-01 00:00:00
abstract：:The clinical advancement of HIV-1 attachment inhibitors was hindered initially by poor bioavailability. Attempts to identify improved candidates revealed that solubility and dissolution-rate-limited absorption are barriers to achieving adequate antiviral plasma levels. This was mitigated by forming nanosized drugs or ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.03.025
更新日期：2014-09-01 00:00:00
abstract：:Polymer-drug conjugates (PDC) have exhibited clinical and commercial success in the field of drug delivery. A polymeric backbone, linker, targeting moiety, and drug constitute the building blocks of PDCs. Current attention is focusing on natural polymeric carriers, in particular the concept of graft copolymers, such a...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2020.06.028
更新日期：2020-09-01 00:00:00
abstract：:Statins are an established therapeutic modality for the treatment of hypercholesterolemia. Although they generally exhibit a good efficacy and tolerability profile, their reputation has been tarnished as a result of reports of myotoxicity and, more recently, observations of proteinuria. The increased incidence of prot...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.03.017
更新日期：2006-05-01 00:00:00
abstract：:Records about the traditional uses of medicinal plants can be considered useful in bioprospecting (i.e., the search for new active agents or lead structures in nature). Several sources like Egyptian papyri, early modern herbals and pharmacopoeias have been studied in this respect. It is proposed to use recordings of b...
journal_title：Drug discovery today
pub_type： 历史文章,杂志文章
doi：10.1016/j.drudis.2016.11.011
更新日期：2017-05-01 00:00:00
abstract：:Regenerative approaches are promising avenues to effectively cure diseases rather than merely treating symptoms, but are associated with concerns around proliferation in other organs. Given that targeted delivery holds the promise of delivering a drug precisely to its desired site of action, usually with the prospect ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.12.004
更新日期：2017-06-01 00:00:00
abstract：:Thermodynamic profiles of ligand binding, particularly enthalpically favored binding signatures, have been suggested as a criterion to support the decision-making process around which compounds to select for further optimization in drug development. The concept was enthusiastically taken up, but turned out to be too s...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2019.01.014
更新日期：2019-04-01 00:00:00
abstract：:Opinions about the therapeutic efficacy of medicinal herbs differ significantly. Some reported herbal efficacies at low doses of active ingredients suggest a need for investigating whether these are because of placebo or multi-ingredient synergistic effects. This review discusses the opinions, methods and outcomes of ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.03.012
更新日期：2009-06-01 00:00:00
abstract：:Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived skin tumor. It is the second-most-common cancer affecting the Caucasian population and is responsible for >20% of all skin-cancer-related deaths. The estimated incidence of non-melanoma skin cancer in the USA is >1000000 cases per year, of which roughl...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.01.023
更新日期：2018-04-01 00:00:00
abstract：:The proces of piecemeal microautophagy of the nucleus describes the way in which autophagy occurs in the nucleus, a realm of the cell once considered to be off limits for autophagy. ...
journal_title：Drug discovery today
pub_type： 新闻
doi：10.1016/s1359-6446(03)02636-9
更新日期：2003-03-15 00:00:00
abstract：:To enable the list of genes and proteins contained within genomic databases to be useful for drug discovery, we need to understand how the genome maps into the phenome. An essential, but not explicitly listed ingredient of the genome is the regulatory interactions between genes and proteins that form a genome-wide net...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02463-7
更新日期：2002-10-15 00:00:00
abstract：:Lack of predictability of clinical efficacy and safety is an important problem facing pharmaceutical research today. Translational PK-PD has the ability to integrate data generated from diverse test platforms during discovery and development in a mechanistic framework. Therefore, successful implementation of translati...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2007.10.002
更新日期：2007-12-01 00:00:00
abstract：:To successfully research and develop an animal pharmaceutical dosage form, a diverse array of issues covering basic medicine, pharmacology and technology must be addressed. Societal concerns regarding animal and public health, as well as the rapidly changing farming and economic environments, provide additional challe...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(02)02362-0
更新日期：2002-08-01 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：:Pulmonary arterial hypertension (PAH) has evolved from an untreatable condition to a disease for which several classes of drugs have now been approved, including various prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Because the pathogenesis of pulmonary hypertension is increasingly u...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.12.003
更新日期：2009-03-01 00:00:00
abstract：:The current understanding of the pathology that underlies pulmonary vascular and right ventricular remodeling in pulmonary hypertension is discussed. Although recent studies underscored the importance of intima and media remodeling and, for the first time, the relevance of perivascular inflammation, much is needed to ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.05.022
更新日期：2014-08-01 00:00:00
abstract：:Medicinal chemistry makes a vital contribution to small molecule drug discovery, and the quality of it contributes directly to research effectiveness as well as to downstream costs, speed and survival in development. In recent years, the discipline of medicinal chemistry has evolved and witnessed many noteworthy contr...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2012.01.010
更新日期：2012-06-01 00:00:00
abstract：:Clinically useful drugs target a relatively small number of proteins that lie within a clearly defined and chemically accessible space. However, many high value biological targets lie outside this chemical space, and an ability to access such 'intractable' targets not amenable to traditional small molecule interventio...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.10.008
更新日期：2013-03-01 00:00:00
abstract：:Natural products have been, and continue to be, a major source of pharmacologically active substances from which drugs can be developed. Currently, tumor necrosis factor-alpha (TNF-alpha) inhibitors from natural origins are being advanced for the treatment of inflammatory disorders. Elevated TNF-alpha synthesis has be...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2006.06.002
更新日期：2006-08-01 00:00:00
abstract：:Successful strategies for the development of monoclonal antibodies require integration of knowledge with respect to target antigen properties, antibody design criteria such as affinity, isotype selection, Fc domain engineering, PK/PD properties and antibody cross-reactivity across species from the early stages of anti...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2008.12.008
更新日期：2009-03-01 00:00:00
abstract：:Acute and chronic cough represent one of the most common symptoms of medical importance but effective pharmacotherapy is, to all intents and purposes, absent. Numerous initiatives targeting the recently discovered tussive pathways are in progress. Here, we review the current antitussive armamentarium and provide an up...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.11.004
更新日期：2013-04-01 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 inhaled delivery of nanomedicines has attracted much attention in the treatment of lung diseases or systemic diseases. However, there is a lack of understanding about their fate upon lung delivery. Thus, the objective of this review is to summarize physicochemical properties affecting the fate of nanoparticles aft...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2019.09.023
更新日期：2020-01-01 00:00:00
abstract：:In this review, we discuss the methodologies and platform technologies for enhancing the oral bioavailability of poorly soluble drugs. We also highlight the mechanisms of formulation technologies for improving desired physicochemical attributes of active substances. We focus on various commercial technologies, along w...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2013.05.007
更新日期：2013-10-01 00:00:00
