Abstract:
:Proline-rich Akt substrate 40kDa (PRAS40) bridges cell signaling between protein kinase B (Akt) and the mammalian target of rapamycin complex 1 (mTORC1). Both Akt and mTORC1 can phosphorylate PRAS40. As a negative regulator of mTORC1, PRAS40 prevents the binding of mTOR to its substrates. The phosphorylation of PRAS40 results in its dissociation from mTORC1 and enhanced mTOR activation. PRAS40 in conjunction with mTORC1 has been closely associated with programmed cell death and is implicated in diabetes mellitus (DM), cardiovascular diseases, cancer, and neurological diseases. Thus, targeting PRAS40 might hold great promise for innovative therapeutic strategies for these diseases.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Chong ZZdoi
10.1016/j.drudis.2016.04.005subject
Has Abstractpub_date
2016-08-01 00:00:00pages
1222-31issue
8eissn
1359-6446issn
1878-5832pii
S1359-6446(16)30109-Xjournal_volume
21pub_type
杂志文章,评审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::Confronted with the need to significantly raise the productivity of remotely located chemistry CROs Pfizer embraced a commitment to continuous improvement which leveraged the tools from both Lean Six Sigma and queue management theory to deliver positive measurable outcomes. During 2012 cycle times were reduced by 48% ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2013.07.017
更新日期:2014-03-01 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::There is an urgent need for fresh approaches to the treatment of bacterial infections because of the changing patterns of infectious disease and the emergence of bacterial strains resistant to current antibiotics. Modification of the cell phenotype to sensitize bacteria to components of the hosts' immune system or to ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(02)02498-4
更新日期:2002-11-01 00:00:00
abstract::The physiological levels of many clinically important proteins are regulated through cellular mechanisms that control the stability and translational efficiency of mRNA. These post-transcriptional processes, which play a critical role in the regulation of gene expression, depend on interactions of specific trans-actin...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.05.009
更新日期:2007-07-01 00:00:00
abstract::The sustained growth of biotechnology in North Carolina has made the state a worldwide leader in biotechnology. ...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/S1359-6446(05)03650-0
更新日期:2005-11-15 00:00:00
abstract::The US Food and Drug Administration (FDA) Expanded Access (EA) Program, which allows for compassionate uses of unapproved therapeutics and diagnostics outside of clinical trials, has gained significant traction during the Coronavirus 2019 (COVID-19) pandemic. While development of vaccines has been the major focus, unc...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.11.025
更新日期:2020-11-27 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative pathology of the central nervous system, mainly involving the selective and progressive loss of dopaminergic neurons from the substantia nigra, resulting in motor and non-motor symptoms. PD remains an incurable ailment; thus, treatments are limited to symptom alleviation...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.09.004
更新日期:2019-11-01 00:00:00
abstract::The biopharmaceutical industry has undergone remarkable changes over the past half century, driven largely by a need to offset the ever-rising costs of developing new medicines. In this report, we aggregated information about the creation and fate of all clinical-stage biopharmaceutical companies, assessing trends ove...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.10.026
更新日期:2021-01-01 00:00:00
abstract::The identification of two biologically active fatty acid amides, N-arachidonoylethanolamine (anandamide) and oleamide, has generated a great deal of excitement and stimulated considerable research. However, anandamide and oleamide are merely the best-known and best-understood members of a much larger family of biologi...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2008.02.006
更新日期:2008-07-01 00:00:00
abstract::Application of humanized xenotransplantation disease models and experimental clinical studies in the context of translational research in drug discovery in dermatology is an opportunity to reduce failure due to lack of efficacy in clinical development stage. ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.10.009
更新日期:2008-03-01 00:00:00
abstract::In this paper, we review the key solutions that enabled evolution of the lead optimization screening support process at Bristol-Myers Squibb (BMS) between 2004 and 2009. During this time, technology infrastructure investment and scientific expertise integration laid the foundations to build and tailor lead optimizatio...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.02.012
更新日期:2012-07-01 00:00:00
abstract::Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of several important endogenous fatty acid amides (FAAs), including anandamide, oleoylethanolamide and palmitoylethanolamide. Because specific FAAs interact with cannabinoid and vanilloid receptors, they are often referred to as 'endocannabinoids' or ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.08.002
更新日期:2009-12-01 00:00:00
abstract::The development of any stem-cell-based therapy (and a potential one for deafness is no exception) relies on the generation of the necessary tools: 'cell drugs' that can be safely manufactured for their clinical application. An increasing body of work has focussed on the identification, in animal models, of potential s...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2010.02.006
更新日期:2010-04-01 00:00:00
abstract::DNA-nanorobot-guided thrombin-inducing tumor infarction (DNA NanorobotTh-ITI) is emerging as a powerful therapeutic strategy for treatment of solid cancers. The technology represents a major advance in the application of DNA nanotechnology for anticancer therapy. More importantly, the technology is being translated fr...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.03.005
更新日期:2020-06-01 00:00:00
abstract::Quercetin is reported to have numerous pharmacological actions, including antidiabetic, anti-inflammatory and anticancer activities. The main mechanism responsible for its pharmacological activities is its ability to quench reactive oxygen species (ROS) and, hence, decrease the oxidative stress responsible for the dev...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.11.001
更新日期:2020-01-01 00:00:00
abstract::Corneal blindness caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide. Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable. Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i.e. biocompatibility, i...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.07.012
更新日期:2013-01-01 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::The use of computational filters for excluding supposedly nonspecific and promiscuous compounds from chemical libraries is a controversial issue, because many drugs used in clinics today would never reach the market if these filters were applied. In part, this conflict could be caused by the paradigm: one-drug-one-tar...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2016.02.004
更新日期:2016-06-01 00:00:00
abstract::For drug discovery, historical experience is always of significance. Through examining the history of traditional medicines, we find that these medicines have more implications for drug discovery than just providing new chemical entities. The history of traditional medicines indicates that they depended more on the co...
journal_title:Drug discovery today
pub_type: 历史文章,杂志文章
doi:10.1016/j.drudis.2008.07.002
更新日期:2009-02-01 00:00:00
abstract::Microarray-based comparative genomic hybridization (array-CGH) has emerged as a revolutionary platform, enabling the high-resolution detection of DNA copy number aberrations. In this article we outline the use and limitations of genomic clones, cDNA clones and PCR products as targets for genomic microarray constructio...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:
更新日期:2004-12-15 00:00:00
abstract::The concept of drug-likeness helps to optimise pharmacokinetic and pharmaceutical properties, for example, solubility, chemical stability, bioavailability and distribution profile. A number of molecular descriptors have emerged as reasonably informative and predictive, for example, the Rule-of-Five. Here, we review so...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.11.007
更新日期:2008-04-01 00:00:00
abstract::Successful drug discovery relies on the selection of drug candidates with good in vivo pharmacokinetic (PK) properties as well as appropriate preclinical efficacy and safety profiles. In vivo PK profiling is often a bottleneck in the discovery process. In this review, we focus on the tiered in vivo PK approaches imple...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2012.09.004
更新日期:2013-01-01 00:00:00
abstract::Manipulation of the human immune system is becoming more of a therapeutic focus as a treatment option or complement. Prominent examples are the increasing use of monoclonal antibodies in combating malignant tumours, and the numerous adoptive immunotherapy trials underway. One important aspect of any use of the human i...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.03.021
更新日期:2014-06-01 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(01)02006-2
更新日期:2001-11-15 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::Cervical cancer is the fourth most common cancer among women worldwide and its development is mainly associated with human papillomavirus infection, a highly sexually transmissible virus. The expression of E6 and E7 viral oncoproteins deregulates cell repairing mechanisms through impairment of tumor suppressor protein...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.07.011
更新日期:2019-10-01 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::Denosumab (Dmab) was the first monoclonal antibody (mAb) approved for the treatment of osteoporosis. It blocks the receptor activator for nuclear factor κB ligand (RANKL) and acts as a potent antiresorptive agent. In contrast to classic antiresorptive agents, Dmab treatment leads to a progressive increase in bone mass...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.09.001
更新日期:2020-09-09 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