Abstract:
:A major strategy used in drug design is the inhibition of enzyme activity. The ability to accurately measure the concentration of the inhibitor which is required to inhibit a given biological or biochemical function by half is extremely important in ranking compounds. Since the concept of the half maximal inhibitory concentration (IC(50)) is used extensively for studying reversible inhibition enzymatic reactions, it is important to clearly understand the experimental design and the mathematical modeling techniques used to generate IC(50) values. The most important part of the experimental design is to measure the rate of production of [P] during the linear phase of the time course of the reaction and to prove that the enzyme-catalyzed reaction is reversible. The most important part of the mathematical modeling is to select the correct model and to have a firm understanding on how to handle outliers in the data. These topics are discussed in greater detail along with a discussion on how much quantitative and mechanistic information can be reasonably deduced from an experiment.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Caldwell GW,Yan Z,Lang W,Masucci JAdoi
10.2174/156802612800672844subject
Has Abstractpub_date
2012-01-01 00:00:00pages
1282-90issue
11eissn
1568-0266issn
1873-4294pii
CTMC-EPub-20120507-007journal_volume
12pub_type
杂志文章,评审abstract::Bacterial infections constitute an always growing health problem worldwide. The resistance to antibiotics of an increasing number of bacterial pathogens necessitates a permanent search for new molecules with different mechanisms of action. Histidine biosynthesis is an ancient pathway found in bacteria, archaebacteria,...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160413140000
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::Pancreatic cancer is a highly malignant tumor with a 5-year survival rate of less than 6%, and incidence increasing year by year globally. Pancreatic cancer has a poor prognosis and a high recurrence rate, almost the same as the death rate. However, the available effective prevention and treatment measures for pancrea...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026619666190828160804
更新日期:2019-01-01 00:00:00
abstract::The field of quantitative structure activity relationships (QSAR) has evolved into an integral tool for pharmaceutical discovery. It is presently an accessible technology, as can be shown by the number papers which are easily found through PubMed literature searches. At one level, QSAR is used routinely and invisibly ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610791111506
更新日期:2010-01-01 00:00:00
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 computationa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026023392968
更新日期:2002-12-01 00:00:00
abstract::The atomic determination of the acetylcholine binding protein (AChBP), a molluscan cholinergic protein, homologous to the amino-terminal extracellular domain of nicotinic receptors (nAChRs), offers opportunities for the modeling of the acetylcholine binding site and its ligands. Recently, we constructed three-dimensio...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451177
更新日期:2004-01-01 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::Peripheral arterial disease (PAD) is due to diffuse atherosclerosis. The pathological process is characterized mainly by the aberrant proliferation of vascular smooth muscle cells and the formation of neointimal lesions. MicroRNAs (miRNAs) are highly conserved non-coding small RNA molecules that regulate a large fract...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113139990107
更新日期:2013-01-01 00:00:00
abstract::Ischemic heart disease and cerebrovascular disease are the leading causes of death in the world. Surprisingly, these diseases are treated by relatively antiquated drugs. However, due to our improved understanding of the underlying pathology of these diseases, and a number of technological advances in tools for drug di...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026013395380
更新日期:2001-06-01 00:00:00
abstract::Kynurenic acid (KYNA), one of the metabolites belonging to the kynurenine pathway, has been described as an important neuroprotective compound, its unbalancing being associated with several pathological conditions. In human brain, the majority of KYNA production is sustained by kynurenine aminotransferase II (KAT II)....
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/156802611794863599
更新日期:2011-01-01 00:00:00
abstract::The recognition that malfunction of the microtubule (MT) associated protein tau is likely to play a defining role in the onset and/or progression of a number of neurodegenerative diseases, including Alzheimer's disease, has resulted in the initiation of drug discovery programs that target this protein. Tau is an endog...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802611794072605
更新日期:2011-01-01 00:00:00
abstract::Hepatitis C virus (HCV) is a major cause of acute hepatitis and chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). No vaccine is currently available to prevent hepatitis C, and the current standard of care (SOC) - pegylated interferon-α (PEG-IFN-α) in combination with ribavirin (RBV) - is o...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610792232051
更新日期:2010-01-01 00:00:00
abstract::Rexinoids are selective ligands for the nuclear receptors known as RXRs. They do not bind to the receptors for all-trans-retinoic acid (RARs). Many new rexinoids have been synthesized and then assayed for their ability to suppress proliferation of cancer cells, to inhibit activation of inflammatory cells of the tumor ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2016-06-16 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::Angiotensin II (AII), Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8, the primary active hormone of the Renin-Angiotensin-System (RAS), is a major vasoconstrictor implicated in the cause of hypertension. To unravel the question of the biologically active conformation(s) of this flexible peptide hormone and to better understa...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026043451375
更新日期:2004-01-01 00:00:00
abstract::Multi-drug resistant bacteria are appearing at an alarming rate and impose significant burdens on healthcare systems worldwide. Cationic peptides have shown great promise as broad spectrum antimicrobial agents with a demonstrated ability to kill resistant bacteria, however, issues such as protease susceptibility and t...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610793176648
更新日期:2010-01-01 00:00:00
abstract::The introduction of biochemical biomarkers in the evaluation of patients with cardiovascular disease has led to practice-changing advancements in the way these patients are diagnosed and managed. Measurements of cardiac troponins or brain-type natriuretic peptide (BNP) and its precursor, N-terminal brain-type natriure...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113139990088
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::G protein coupled receptors (GPCRs) are membrane proteins coupled with G proteins through which they transmit signals to the cytoplasm. Approximately 30% of pharmaceuticals target these receptors, even though crystal structures were scarce at the time. Furthermore, an additional 15% of GPCRs have yet to be exploited f...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150915121324
更新日期:2016-01-01 00:00:00
abstract::Although bioactivation is a well-documented process and the role of active metabolites in the drug discovery field has long been recognized, drug metabolites are usually ignored in virtual screening campaigns oriented to drug repositioning. The present article discusses different issues related to overlooking of the a...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160216155043
更新日期:2016-01-01 00:00:00
abstract::Three distinct chemical classes for the control of gastrointestinal nematodes are available: benzimidazoles, imidazothiazoles, and macrocyclic lactones. The relentless development of drug resistance has severely limited the usefulness of such drugs and the search for a new class of compounds preferably with a differ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026023393705
更新日期:2002-07-01 00:00:00
abstract::This article focuses on the GDNF family of neurotrophic factors as a potential new class of therapeutics for neuropathic pain, with a particular emphasis on the ligands, artemin and GDNF. In vivo activity of the ligands, expression of ligands and receptors after peripheral nerve injury, and modulation of nerve injury-...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026054367593
更新日期:2005-01-01 00:00:00
abstract::Metabolic syndrome (MS) is a modern medical condition characterized by central obesity, hyperglycaemia, hypercholesterolemia and hypertension. The beneficial effects of mushrooms in lowering the symptoms of MS were known from both traditional and conventional medicine. Edible mushrooms, their extracts, polysaccharide ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15680266113136660196
更新日期:2013-01-01 00:00:00
abstract::Nanotechnology is revolutionizing the development of different branches of science. The investigation of nanomaterials in the battle against cancer is not an exception. The main goal of this contribution is to bring an overview about the types of organic and inorganic nanomaterials that are under investigation for its...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026614666140118213316
更新日期:2014-03-01 00:00:00
abstract::With the global aging population, Alzheimer's disease, Parkinson's disease and mild cognition impairment are increasing in prevalence. The success of rapamycin as an agent to extend lifespan in various organisms, including mice, brings hope that chronic mTOR inhibition could also refrain age-related neurodegeneration....
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150610125856
更新日期:2015-01-01 00:00:00
abstract::Transition metal complexes with terpyridine ligands have attracted a widespread interest with respect to biomedical applications: [(tpy)PtCl]Cl and [(tpy)RuCl(3)] are potent anti-tumor agents with activities comparable to those of cisplatin and carboplatin. The Ru(II) complexes feature a high potential as reactive pro...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612799078919
更新日期:2012-01-01 00:00:00
abstract:: ...
journal_title:Current topics in medicinal chemistry
pub_type: 社论
doi:10.2174/156802661815181101110430
更新日期:2018-01-01 00:00:00
abstract::Aromatic polyketides represent important members of the family of polyketides, which have displayed a wide assortment of bioactive properties, such as antibacterial, antitumor, and antiviral activities. Bacterial aromatic polyketides are mainly synthesized by type II polyketide synthases (PKSs). Whereas malonyl-CoA is...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802609789941906
更新日期:2009-01-01 00:00:00
abstract::The replication cycle of human immunodeficiency virus (HIV) is divided into an early and a late phase. Most of the steps of the cycle have been targeted in antiviral therapy, although the drugs currently available for clinical use are only effective against two replication enzymes of the virus, either against the reve...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026033451781
更新日期:2003-01-01 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