Abstract:
:There exists a huge attrition rate of molecules in clinical trials. It was expected that high-throughput screening and combinatorial chemistry would make the task of producing drugs easier. However, the efforts of the past decade have not been an unvarnished success. As a result, a lot of experimental and computational efforts are currently being directed at determining the basic requirements for a molecule to become a drug. Here we will review the physiological, structural, and other requirements for obtaining a molecule that will be successful in the clinic. Following this we will provide a description, analysis, and commentary on the computational efforts in this direction. We will focus both on the traditional computational chemistry perspective of starting from the structure of the molecule as well as the traditional computational pharmaceutical scientist's perspective of physiologically based simulations. We end with a few comments about the future and some ideas on re-organizing the pharmaceutical enterprise.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Ajaydoi
10.2174/1568026023392968keywords:
subject
Has Abstractpub_date
2002-12-01 00:00:00pages
1273-86issue
12eissn
1568-0266issn
1873-4294journal_volume
2pub_type
杂志文章,评审abstract::Psychiatric diagnosis has long been perceived as more of an art than a science since its foundations lie within the observation, and the self-report of the patients themselves and objective diagnostic biomarkers are lacking. Furthermore, the diagnostic tools in use not only stray away from the conventional medical fra...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026620666200131095328
更新日期:2020-01-01 00:00:00
abstract::In this review the conformational studies of natural enkephalins (H-Tyr-Gly-Gly-Phe-Met-OH; the [Met(5)]enkephalin and H-Tyr-Gly-Gly-Phe-Leu-OH; the [Leu(5)]enkephalin), their acyclic and cyclic analogues, including those carried out in our laboratory, performed by experimental and theoretical methods and their combin...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451591
更新日期:2004-01-01 00:00:00
abstract::Untargeted metabolomics is a promising approach for reducing the significant attrition rate for discovering and developing drugs in the pharmaceutical industry. This review aims to highlight the practical decision-making value of untargeted metabolomics for the advancement of drug candidates in drug discovery/developm...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170707130032
更新日期:2017-01-01 00:00:00
abstract::Choline kinase (CK) is a homodimeric enzyme that catalyses the transfer of the ATP γ-phosphate to choline, generating phosphocholine and ADP in the presence of magnesium. Several isoforms of CK are present in humans but only the HsCKα has been associated with cancer and validated as a drug target to treat this disease...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026614666141216093337
更新日期:2014-01-01 00:00:00
abstract::Target-Related Affinity Profiling (TRAP) is a computational drug discovery technology that is based on 'affinity fingerprints', which are molecular descriptors derived from the protein binding preferences of small molecules. The underlying concepts of TRAP are reviewed. Affinity fingerprints are compared to molecular ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026053828394
更新日期:2005-01-01 00:00:00
abstract::The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally α-amino acids with one or more stereogenic centers due to st...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611795164990
更新日期:2011-01-01 00:00:00
abstract::Artemisinin is isolated from Artemisia annua L. with peroxide-containing sesquiterpene lactone structure. Because of its unique structural characteristics and promising anticancer, antivirus activities, it has recently received increasing attention. The aim of this review is to summarize recent discoveries of artemisi...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026619666190122144217
更新日期:2019-01-01 00:00:00
abstract::Viral entry, the first process in the reproduction of viruses, primarily involves attachment of the viral envelope proteins to membranes of the host cell. The crucial components that play an important role in viral entry include viral surface glycoprotein gp120, viral transmembrane glycoprotein gp41, host cell glycopr...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026619666190712204050
更新日期:2019-01-01 00:00:00
abstract::The first-ever World Chagas Disease Day, celebrated in April 14, 2020, is a key initiative to raise awareness of the impact of this neglected tropical disease (NTD). This landmark comes along with the first World NTD Day and the new WHO Road Map on NTDs for 2021-2030. ...
journal_title:Current topics in medicinal chemistry
pub_type: 社论
doi:10.2174/156802662017200624115305
更新日期:2020-01-01 00:00:00
abstract::Efflux pumps of the Resistance Nodulation Division (RND) superfamily play a major role in the intrinsic and acquired resistance of Gram-negative pathogens to antibiotics. Moreover, they are largely responsible for multi-drug resistance (MDR) phenomena in these bacteria. The last decade has seen a sharp increase in the...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113136660220
更新日期:2013-01-01 00:00:00
abstract::Antimicrobial peptides (AMPs) are a class of peptides found across a wide array of organisms that play key roles in host defense. AMPs induce selective death in target cells and orchestrate specific or nonspecific immune responses. Many AMPs exhibit native anticancer activity in addition to antibacterial activity, and...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666201021141401
更新日期:2020-01-01 00:00:00
abstract::Penile erection is a complex physiologic event resulting from the interactions of the nervous system on a highly specialized vascular organ. Activation of central nervous system melanocortinergic (MC) receptors with either endogenous or synthetic melanotropic ligands may initiate and/or facilitate spontaneous penile e...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::Chemical genomics combines chemistry with molecular biology as a means of exploring the function of unknown proteins or identifying the proteins responsible for a particular phenotype induced by a small cell-permeable bioactive molecule. Chemical genomics therefore has the potential to identify and validate therapeuti...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612801319025
更新日期:2012-01-01 00:00:00
abstract::Histone deacetylases (HDACs) have recently emerged as key elements in epigenetic control of gene expression. Due to the implication of HDACs in a variety of diseases ranging from cancer to neurodegenerative disorder, HDAC inhibitors have received increased attention in recent years. Over the last few decades, a myriad...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666141208105614
更新日期:2015-01-01 00:00:00
abstract::Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) controlling physiological processes as learning and memory. However, the overactivation of glutamatergic neurotransmission is often related to various CNS chronic and acute diseases (epilepsy, ischaemia, Parkinson, etc.). ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612800229242
更新日期:2012-01-01 00:00:00
abstract::After the identification of the anti-inflammatory properties of VA5-13l (2-benzyl-1- methyl-5-nitroindazolinone) in previous investigations, some of its analogous compounds were designed, synthesized and evaluated in two anti-inflammatory methods: LPS-enhanced leukocyte migration assay in zebrafish; and 12-O-tetradeca...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666180119125255
更新日期:2018-02-09 00:00:00
abstract::Escherichia coli purine nucleoside phosphorylase (PNP) catalyzes the cleavage of 9-(2-deoxy-beta-D-ribofuranosyl)-6-methylpurine (MeP-dR), while human PNP does not. MeP-dR is well tolerated while the cleavage product, 6-methylpurine (MeP), is highly cytotoxic. This clinical profile suggests an anticancer gene therapy ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802605774463105
更新日期:2005-01-01 00:00:00
abstract::The task of rationally designing vaccines that can effectively impact on the survival of cancer patients remains challenging. Monoclonal antibodies and T cell receptors have proven to be viable templates for the application of pharmacophore design principles to develop antigens and immunogens as these immune system mo...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802605774370928
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Neuraminidase inhibitors (NAIs) are the only class of antivirals in clinical use against influenza virus approved worldwide. However, approximately 1-3% of circulating strains present resistance mutations to oseltamivir (OST), the most used NAI. Therefore, it is important to catalogue new molecules to inhibi...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666191219150738
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Development of acetyl- (AChE) and butyrylcholinesterase (BuChE) inhibitors belongs to viable strategies for the treatment of dementia and other diseases related to decrease in cholinergic neurotransmission. OBJECTIVE:That is why we designed twenty-two analogues of a dual AChEBuChE salicylanilide inhibitor, ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666200819154722
更新日期:2020-01-01 00:00:00
abstract::Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca²⁺ mobilizing endogenous compound known to date. Although its Ca²⁺ releasing activity has been demonstrated in many cell types and in response to different extracellular stimuli, several aspects of NAADP signaling are unclear. This overview foc...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113136660212
更新日期:2013-01-01 00:00:00
abstract::The dynamics of gene expression are regulated by histone acetylases (HATs) and histone deacetylases (HDACs) that control the acetylation state of lysine side chains of the histone proteins of chromatin. The catalytic activity of these two enzymes remodels chromatin to control gene expression without altering gene sequ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802609788085241
更新日期:2009-01-01 00:00:00
abstract::Chronic hepatitis B virus (HBV) infection affects about 400 million people worldwide. The development of nucleoside analogs that inhibit HBV polymerase provides an important approach for treating HBV infection. The approval of lamivudine, adefovir and entecavir represents a cornerstone of hepatitis B therapy. However,...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802606777303667
更新日期:2006-01-01 00:00:00
abstract::The scaffold protein Axin plays important roles in multiple signaling pathways through mediating the formation of different signaling complexes. Axin is best known for its role as a negative regulator in Wnt/β-catenin pathway. Aberrant activation of the key components in Wnt/β-catenin pathway including Axin has been l...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026616666160622220245
更新日期:2016-01-01 00:00:00
abstract::Neuronal nicotinic acetylcholine ion channel receptors (nAChRs) exist as several subtypes and are involved in a variety of functions and disorders of the central nervous system (CNS), such as Alzheimer's and Parkinson's diseases. The lack of reliable information on the 3D structure of nAChRs prompted us to focus effor...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451384
更新日期:2004-01-01 00:00:00
abstract::Computational toxicity modeling can have significant impact in the drug discovery process, especially when utilized as a sentinel filter for common drug safety liabilities, such as mutagenicity, carcinogenicity and teratogenicity. This review will focus on the strengths and limitations of the current computational mod...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026013395074
更新日期:2001-09-01 00:00:00
abstract::Biomarkers in the clinical oncology field can have tremendous therapeutic impact especially if the marker is detected before clinical symptoms. This impact can be extended to the evaluation of clinical oncology treatments allowing evaluation of potential compounds to determine their efficacy in the disease treatment. ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802605774297074
更新日期:2005-01-01 00:00:00
abstract::Variable selection is a procedure used to select the most important features to obtain as much information as possible from a reduced amount of features. The selection stage is crucial. The subsequent design of a quantitative structure-activity relationship (QSAR) model (regression or discriminant) would lead to poor ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802608786786552
更新日期:2008-01-01 00:00:00
abstract::Alzheimer's disease (AD) is an irreversible multifaceted neurodegenerative disorder that gradually degrades neuronal cells. Presently, it is the most common reason for the memory loss and dementia in older individuals. It is patho-physiologically described by extracellular amyloid beta (Aβ) deposition, intracellular n...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170103163715
更新日期:2017-01-01 00:00:00
abstract::Human multidrug resistance protein (MRP/ABCC) family contains 9 members (MRP1-9) which transport a structurally diverse array of anticancer and antimicrobial drugs and several important endogenous substances including prostaglandins (PGs) and leukotrienes (LTs) with different substrate specificity. MRP1-5 can collecti...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610792928040
更新日期:2010-01-01 00:00:00