Abstract：
:Much attention has focused on the development of protein kinases as drug targets to treat a variety of human diseases including diabetes, cancer, hypertension and arthritis. To date, Gleevec is one example of a drug targeting protein that has successfully treated human cancer. Several other protein kinase inhibitors are in clinical development. However, protein kinases are in fact part of a larger collection of some 2000 distinct proteins expressed by the genome that like the protein kinases also bind purines (the purinome), either to be utilized as substrates or as co-factors in the form of NAD, NADP and co-enzyme A. The solution structures of many representative gene family members within the purinome show these proteins bind purines in a similar orientations to that observed in all protein kinases. Several non-protein kinase purine utilizing proteins are established drug targets such as HMG CoA reductase, dihydrofolate reductase, phosphodiesterase and HSP90. Searches of OMIM identifies many purine utilizing enzymes that are associated with inborn errors in metabolism. Inhibition of any one of which by a drug could lead to an undesirable side effect. The purinome is therefore somewhat of a drug discovery mixed blessing. It is a rich source of therapeutic targets, but also contains a large collection of diverse proteins whose inhibition could result in an adverse outcome. Drug discovery within the purinome should therefore encompass strategies that enable broad assessment of selectivity across the entire purinome at the earliest stages of the discovery process. In this article we review the purinome within the context of drug discovery and discuss approaches for avoiding off target binding during the discovery/lead optimization process with particular emphasis on use of proteome mining technology.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Haystead TAdoi
10.2174/156802606777812059subject
Has Abstractpub_date
2006-01-01 00:00:00pages
1117-27issue
11eissn
1568-0266issn
1873-4294journal_volume
6pub_type
杂志文章,评审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：:One year after its first outbreak reported in China, coronavirus disease 2019 (COVID-19) pandemic is still sweeping the World causing serious infections and claiming more fatalities. COVID-19 is caused by the novel corona virus SARS-CoV-2, which belongs to the genus Betacoronavirus (β-CoVs) which is of greatest clinic...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
doi：10.2174/1568026621666210119111409
更新日期：2021-01-18 00:00:00
abstract：:In general perturbation methods starts with a known exact solution of a problem and add "small" variation terms in order to approach to a solution for a related problem without known exact solution. Perturbation theory has been widely used in almost all areas of science. Bhor's quantum model, Heisenberg's matrix mecha...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026611313140011
更新日期：2013-01-01 00:00:00
abstract：:Estrogens control a wide number of aspects of human physiology and play a key role in multiple diseases, including cancer. Estrogens act by binding to and activating the cognate receptor (ER), however numerous studies have revealed that the G protein-coupled receptor named GPR30/GPER mediates also estrogen signals. As...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
doi：10.2174/1568026615666150317221549
更新日期：2015-01-01 00:00:00
abstract：:In this paper we provide an overview of the status of various colchicine derivatives in preclinical development with special focus on their anti-cancer activity. We discuss several groups of compounds that have been designed to differentially bind with specific affinities for tubulin β isotypes, especially in regard t...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026617666170104143618
更新日期：2017-01-01 00:00:00
abstract：:The dopamine transporter (DAT) is a target for the development of pharmacotherapies for a number of central disorders including Parkinson's disease, Alzheimer's disease, schizophrenia, Tourette's syndrome, Lesch-Nyhan disease, attention deficit hyperactivity disorder (ADHD), obesity, depression, and stimulant abuse as...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/156802606778249775
更新日期：2006-01-01 00:00:00
abstract：:The connection of microbial biosynthetic gene clusters to the small molecule metabolites they encode is central to the discovery and characterization of new metabolic pathways with ecological and pharmacological potential. With increasing microbial genome sequence information being deposited into publicly available da...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026616666151012111046
更新日期：2016-01-01 00:00:00
abstract：:The first proteolytic step in the processing of amyloid precursor protein (APP) to amyloid-beta (Abeta) in the brain is performed by beta-site APP cleaving enzyme (BACE1). This enzyme is a membrane bound aspartic protease with high homology of the catalytic domain to renin and pepsin and of yet unknown physiologic fun...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026024607490
更新日期：2002-04-01 00:00:00
abstract：: ...
journal_title：Current topics in medicinal chemistry
pub_type： 社论
doi：10.2174/1568026619666181120121528
更新日期：2018-01-01 00:00:00
abstract：AIM:The aim of this study is to synthesize, characterize and biological evaluation of 3-ethyl 5- methyl2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives. BACKGROUND:An efficient synthesis of two series of novel carbamate and sulfonamide derivatives of amlodipine, 3-ethyl 5-methyl 2...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
doi：10.2174/1568026619666191105100959
更新日期：2019-01-01 00:00:00
abstract：:Emergence of drug-resistant viral strains is one of the major milestones and the main cause for the failure of antiretroviral therapy. Combination of different anti-HIV agents has become the standard clinical practice to keep the viral load at low or even undetectable levels and to prevent emergence of virus-drug resi...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026043388600
更新日期：2004-01-01 00:00:00
abstract：:Sphingosine 1-phosphate (S1P) evokes a plethora of physiological responses by stimulating members of a G protein-coupled receptor family, known as S1P receptors. Currently five different mammalian S1P receptor subtypes, S1P₁₋₅, each with a different cellular expression pattern, were identified. The S1P₁ receptor in pa...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026611109060726
更新日期：2011-01-01 00:00:00
abstract：:PLA2 enzyme catalyses the hydrolysis of cellular phospholipids at the sn-2 position to liberate arachidonic acid and lysophospholipid to generate a family of pro-inflammatory eicosanoids and platelet activating factor. The generation of pro-inflammatory eicosanoids involves a series of free radical intermediates with ...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/156802607780487623
更新日期：2007-01-01 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：:This review mainly covers last five year literature on CCK1R agonists and antagonists. These CCK1R ligands have been found following the two usual and complementary strategies for drug discovery: rational design based on structure activity relationships on the CCK-7 and CCK-4 peptide sequences of the endogenous ligand...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/156802607780960537
更新日期：2007-01-01 00:00:00
abstract：:Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate Dehydrogenase Kinase (PDK) is a gatekeeper en...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026618666180523105756
更新日期：2018-01-01 00:00:00
abstract：:Pronucleotides represent a promising alternative to improve the biological activity of nucleoside analogues against different viral diseases. The basic idea is to achieve nucleotide delivery into cells, bypassing limitations with intracellular formation of nucleotides from their nucleoside precursors. The cycloSal-con...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026023393183
更新日期：2002-10-01 00:00:00
abstract：:Trichomoniasis, one of the most common non-viral sexually transmitted infections worldwide, is caused by the parasite Trichomonas vaginalis. The pathogen colonizes the human urogenital tract, and the infection is associated with complications such as adverse pregnancy outcomes, cervical cancer, and an increase in HIV ...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
doi：10.2174/1568026620999200904122212
更新日期：2021-01-01 00:00:00
abstract：:Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metaboli...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
doi：10.2174/1568026617666170713172331
更新日期：2017-01-01 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：:The computational assessment of drug metabolism has gained considerable interest in pharmaceutical research. Amongst others, machine learning techniques have been employed to model relationships between the chemical structure of a compound and its metabolic fate. Examples for these techniques, which were originally de...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/156802606778108915
更新日期：2006-01-01 00:00:00
abstract：:KRAS is the most common oncogene to be mutated in lung cancer, and therapeutics directly targeting KRAS have proven to be challenging. The mutations of KRAS are associated with poor prognosis, and resistance to both adjuvant therapy and targeted EGFR TKI. EGFR TKIs provide significant clinical benefit for patients who...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026619666190902150555
更新日期：2019-01-01 00:00:00
abstract：:Ropivacaine, the S-(-)-enantiomer of N-(2,6-dimethylphenyl)-1-propyl-2-piperidinecarboxamide is a new long-acting local anesthetic. This review demonstrates that it is effective in brachial plexus anesthesia. It is at least as efficient as bupivacaine in terms of quality, duration of analgesia, anesthesia, and motor b...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026013395326
更新日期：2001-08-01 00:00:00
abstract：BACKGROUND:Farnesol is an acyclic sesquiterpene alcohol, endogenously synthesized via the ergosterol pathway. It is a quorum sensing molecule (QSM) that was first discovered in C. albicans, and is involved in the inhibition of hyphae formation. METHODS:This review focuses on the comprehensive details of occurrence, ch...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026619666181210124159
更新日期：2018-01-01 00:00:00
abstract：:A proper balance between oxidants and antioxidants is necessary in maintaining health and longevity. Alterations in this balance may result in oxidative stress causing functional disorders and diseases. Oxidative stress is considered to play a vital role in the pathogenesis of diabetes and its complications. Flavanone...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026615666141209163013
更新日期：2015-01-01 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：:Organic nitrates, such as nitroglycerin, have been used in clinical practice for more than one century for the treatment of angina, even before the identification of Nitric Oxide (NO) as the so-called Endothelium Derived Relaxing Factor (EDRF). Recently, multiple functions of this molecule in biology and pathophysiolo...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026054679335
更新日期：2005-01-01 00:00:00
abstract：:As master regulators of lipid metabolism the peroxisome proliferator activated receptor (PPAR) family controls a wide variety of cellular processes, and thus it is not surprising that a large effort has focussed on discovering agents to pharmacologically modulate activity of these receptors. Early generation PPAR liga...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章,评审
doi：10.2174/1568026033451673
更新日期：2003-01-01 00:00:00
abstract：BACKGROUND:The impact of fungal infections on human health has increased considerably within a past few decades. Although drugs with antifungal properties are available, but they are less effective and are associated with side effects. OBJECTIVE AND METHOD:To screen the bacterial isolates from Sesamum indicum and to i...
journal_title：Current topics in medicinal chemistry
pub_type： 杂志文章
doi：10.2174/1568026618666180206102140
更新日期：2018-01-01 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
