Abstract：
:The drug-likeness of a compound is a key factor during the initial phases of drug discovery. It can be defined as the similarity between compounds and drugs. Here, we collate research related to the fraction of sp3 carbon atoms (Fsp3), including related high-throughput screening (HTS) cases, structural modifications based on Fsp3, and strategies to improve it. We also introduce new synthetic methods for spirocyclic scaffolds. It is likely that the reasonable rigidity of spirocyclic scaffolds will provide a new generation of drug candidates.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Wei W,Cherukupalli S,Jing L,Liu X,Zhan Pdoi
10.1016/j.drudis.2020.07.017subject
Has Abstractpub_date
2020-07-24 00:00:00eissn
1359-6446issn
1878-5832pii
S1359-6446(20)30297-Xpub_type
杂志文章,评审abstract：:Active immunotherapy of neurodegenerative proteinopathies, such as Alzheimer's disease, requires a Th2 antibody immune response with exclusion of damaging inflammatory Th1 immunity. Because these diseases affect the elderly whom, owing to immunosenescence, are frequently immune compromised, a successful therapy would ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.02.015
更新日期：2014-07-01 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：:For many years, there has been spirited debate as to the relative importance of environmental and genetic factors in the pathogenesis of cancer. Current efforts to annotate the human genome for germ-line genetic variants should establish the foundation for dissecting the contribution of genetics to the risk for cancer...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03179-4
更新日期：2004-07-15 00:00:00
abstract：:Gastrointestinal patch systems with integrated multifunctions could surmount the challenges associated with conventional drug delivery. Several gastrointestinal patch systems provide bioadhesion, drug protection and unidirectional release. This combination of function could improve the overall oral bioavailability of ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03489-6
更新日期：2005-07-01 00:00:00
abstract：:14-3-3 proteins regulate intracellular signaling pathways, such as signal transduction, protein trafficking, cell cycle, and apoptosis. In addition to the ubiquitous roles of 14-3-3 isoforms, unique tissue-specific functions are also described for each isoform. Owing to their role in regulating cell cycle, protein tra...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.09.012
更新日期：2016-02-01 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：:Antibodies (Abs) are regarded as a newly emerging form of therapeutics that can provide passive protection against influenza. Although the application of genomics in clinics has increased dramatically, the number of therapeutics available for the treatment of many diseases remains insufficient. To translate genomics i...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2016.06.008
更新日期：2016-10-01 00:00:00
abstract：:Epigenetic covalent modifications of DNA and chromatin proteins strongly affect gene expression and cellular activity, and epigenetic misregulation occurs in several diseases, especially cancer. First-generation drugs targeting the relatively promiscuous DNA methylation and histone acetylation modifiers have had succe...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.10.010
更新日期：2010-01-01 00:00:00
abstract：:The focus of high-throughput drug discovery has progressed through the genome and the transcriptome and is now moving towards more difficult problems in assessing the proteome, glycome and metabolome. Microarrays are currently the major tool in the assessment of gene expression via cDNA or RNA analysis; however, they ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/s1359-6446(03)02773-9
更新日期：2003-07-15 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：:The lack of structural information on hepatitis C virus (HCV) surface proteins has so far hampered the development of effective vaccines. Recently, two crystallographic structures have described the core portion (E2c) of E2 surface glycoprotein, the primary mediator of HCV entry. Despite the importance of these studie...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2014.08.011
更新日期：2014-12-01 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：:Drugs targeting infectious diseases have greatly improved public health. A study to evaluate all US Food and Drug Administration (FDA)-approved new molecular entities (NMEs) reveals that the number of new agents targeting infectious disease peaked during the 1990s and declined rapidly thereafter. Molecules targeting b...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2014.07.005
更新日期：2014-09-01 00:00:00
abstract：:Nonclinical safety testing of new biotherapeutic entities represents its own challenges and opportunities in drug development. Hot topics in this field have been discussed recently at the 2nd Annual BioSafe European General Membership Meeting. In this feature article, discussions on the challenges surrounding the use ...
journal_title：Drug discovery today
pub_type：
doi：10.1016/j.drudis.2013.08.003
更新日期：2013-12-01 00:00:00
abstract：:A fierce dispute has arisen between the supporters of phenotypic and target-focused screening regarding which path grants the higher probability of successful drug development. A chance to reconcile these two approaches lies in successful target deconvolution (TD) after phenotypic screens. But, despite the panoply of ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2018.10.009
更新日期：2019-02-01 00:00:00
abstract：:Drug discovery is shifting focus from industry to outside partners and, in the process, creating new bottlenecks. Technologies like high throughput screening (HTS) have moved to a larger number of academic and institutional laboratories in the USA, with little coordination or consideration of the outputs and creating ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2012.10.007
更新日期：2013-03-01 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：: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：:Current multiparameter optimization (MPO) strategies make use of few experimental physicochemical descriptors (i.e., solubility at physiological pH and lipophilicity in the octanol/water system). Here, we show how new trends in drug discovery (i.e., large and flexible molecules for 'difficult' targets) call for the in...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2016.11.017
更新日期：2017-06-01 00:00:00
abstract：:With the aging of the general population, there is an increasing need for bone defect repair, prompting the development of reliable alternatives to autologous bone grafting, without the usually associated major drawbacks (i.e., limited volume and severe postoperative pain). Given the crucial role that miRNAs appear to...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2017.04.007
更新日期：2017-07-01 00:00:00
abstract：:There is currently a marketed drug for nearly every nuclear receptor for which the natural ligand has been identified. However, because of the complexity of signal transduction by this class of ligand-regulated transcription factors, few of these drugs have been optimized for pharmaceutical effectiveness. Over the pas...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(04)03201-5
更新日期：2004-09-01 00:00:00
abstract：:Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with 'two-target' functionality can interfere with multiple surface receptors or ligands associated, for example with cancer, proliferation or inflammatory processes. BsAbs can also pl...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2015.02.008
更新日期：2015-07-01 00:00:00
abstract：:High-information screening formats, using more physiologically relevant cellular models and readout approaches, are slowly replacing traditional, target-orientated approaches in drug discovery programs. With improved access to primary cells, as well as label-free, non-intrusive methods of compound interrogation (such ...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2010.02.010
更新日期：2010-05-01 00:00:00
abstract：:We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2015.06.015
更新日期：2015-11-01 00:00:00
abstract：:A more complete understanding of the mechanisms that drive autoimmune diseases has begun to be translated into therapeutic options with significant clinical consequences. A clear example of this is the introduction of biological therapies, which have provided new therapeutic avenues, as well as validated the mediators...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2009.07.002
更新日期：2009-10-01 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：:Patients with severe asthma suffer persistent symptoms and/or frequent exacerbations despite high-intensity treatment. Their severe unrelenting symptoms have a huge impact on healthcare resources owing to frequent hospital admissions and requirement for intensive treatments. Consequently, there is an undeniable need f...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/j.drudis.2012.01.012
更新日期：2012-06-01 00:00:00
abstract：:Drug discovery is a time consuming and costly process. Recently, a trend towards the use of in silico computational chemistry and molecular modeling for computer-aided drug design has gained significant momentum. This review investigates the application of free and/or open-source software in the drug discovery process...
journal_title：Drug discovery today
pub_type： 杂志文章,评审
doi：10.1016/S1359-6446(05)03692-5
更新日期：2006-02-01 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：:This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. ...
journal_title：Drug discovery today
pub_type： 杂志文章
doi：10.1016/j.drudis.2012.05.014
更新日期：2012-06-01 00:00:00
