Abstract:
:In this review the preclinical medicinal chemistry, biochemistry and clinical results achieved in the treatment of prostatic disease with dutasteride, a dual inhibitor of type 1 and type 2,5alpha-reductase are described. During the discovery phase, dutasteride was optimized to inhibit both forms of human 5 alpha-reductase (5AR) via extensive structure activity relationship studies versus the cloned human isozymes. Dutasteride has subsequently been shown to improve disease measures in patients with symptomatic benign prostatic hyperplasia (BPH) in three randomized, placebo-controlled, Phase III clinical studies lasting for 2 years. Additionally, dutasteride is now under study for the ability to reduce the incidence of prostate cancer in men at high risk of the disease--an indication where the unique dual inhibitor nature, half-life and tolerability of dutasteride may be especially significant factors in determining treatment success. The connections between preclinical drug design and clinical outcomes during the discovery and development of dutasteride are exemplified.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Frye SVdoi
10.2174/156802606776743101subject
Has Abstractpub_date
2006-01-01 00:00:00pages
405-21issue
5eissn
1568-0266issn
1873-4294journal_volume
6pub_type
杂志文章,评审abstract::Millions of deaths each year are attributed to malaria worldwide. Transmitted through the bite of an Anopheles mosquito, infection and subsequent death from the Plasmodium species, most notably P. falciparum, can readily spread through a susceptible population. A malaria vaccine does not exist and resistance to virtua...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612799362922
更新日期:2012-01-01 00:00:00
abstract::Apatamer technology has been around for a quarter of a century and the field had matured enough to start seeing real applications, especially in the medical field. Since their discovery, aptamers rapidly emerged as key players in many fields, such as diagnostics, drug discovery, food science, drug delivery and therape...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150413153717
更新日期:2015-01-01 00:00:00
abstract::Anticancer drug screening can accelerate drug discovery to save the lives of cancer patients, but cancer heterogeneity makes this screening challenging. The prediction of anticancer drug sensitivity is useful for anticancer drug development and the identification of biomarkers of drug sensitivity. Deep learning, as a ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666200710101307
更新日期:2020-01-01 00:00:00
abstract::Monoacylglycerol lipase (MAGL) has been recently proposed as the main enzymatic activity responsible for the in vivo hydrolysis of the most abundant endocannabinoid in the brain, the 2-arachidonoylglycerol (2-AG). The endocannabinoids, mainly anandamide (AEA) and 2-AG, are a class of lipid messengers that modulate a b...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802608783498032
更新日期:2008-01-01 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::In 2010, the National Institutes of Health (NIH) established the Therapeutics for Rare and Neglected Diseases (TRND) program within the National Center for Advancing Translational Sciences (NCATS), which was created to stimulate drug discovery and development for rare and neglected tropical diseases through a collabor...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026613666131127160118
更新日期:2014-01-01 00:00:00
abstract::Our understanding of glutamatergic transmission in the central nervous system has been greatly expanded with the discovery and investigation of the metabotropic glutamate receptor family. Complementing the ionotropic glutamate-gated ion channels, these G-protein coupled receptors play critical roles in neuronal and gl...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026054750254
更新日期:2005-01-01 00:00:00
abstract::Inflammation is a complex phenomenon necessary in human defense mechanisms but also involved in the development of some human diseases. The discovery of cyclooxygenase-2 (COX- 2) improved the pharmacology of nonsteroidal anti-inflammatory drugs (NSAID) giving a clear mechanism for prostaglandin regulation in vivo and ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026617666170821124947
更新日期:2017-01-01 00:00:00
abstract::Drugs with poor lipid and water solubility are some of the most challenging to formulate in nanocarriers, typically resulting in low encapsulation efficiencies and uncontrolled release profiles. PEGylated nanocapsules (PEG-NC) are known for their amenability to diverse modifications that allow the formation of domains...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026614666140329224716
更新日期:2014-01-01 00:00:00
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::Plasma glucose is continuously filtered through the glomerulus and then is reabsorbed via the transcellular transport system of proximal tubules in the kidney. The glucose reabsorption system in the kidney is mediated by sodium-dependent glucose cotransporters (SGLTs). Most of filtered glucose is reabsorbed by the low...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610790980567
更新日期:2010-01-01 00:00:00
abstract::Thermolysin (TLN) and other thermolysin-like zinc metalloproteinases (TLPs),are important virulence factors for pathogenesis of bacterial infections by suppressing the innate immune system of the host. Therapeutic inhibition ofTLPs is believed to be a novel strategy inthe development of a new generation antibiotics.In...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/156802612803989246
更新日期:2012-01-01 00:00:00
abstract::The adenosine A(2A) receptor is a member of the G protein-coupled receptor family and mediates multiple physiological effects of adenosine, both at the central nervous system and at peripheral tissues. Increasing evidence relates the A(2A) receptor with several pathological conditions such as neurodegenerative disorde...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802610791268765
更新日期:2010-01-01 00:00:00
abstract::Over the past decades, a tremendous rise in invasive fungal infection diseases attributed to the yeast Candida albicans in immunocompromised individuals poses a seriously challenging issue. Another concern is the emergence of multi-drug resistant pathogens to the existing medicines due to their overuse and misuse. It ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026620666200704140107
更新日期:2020-01-01 00:00:00
abstract::As the first stable tachysterol analogs, 14-epi-19-nortachysterol and its 2-substituted derivatives were synthesized using the Stille coupling reaction between the A-ring precursor (three vinylstannanes) and the CD-ring vinyl trifrate. Among them, the 2-methylidene group was hydrogenated with Wilkinson's catalyst regi...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1568026615666141208103741
更新日期:2014-01-01 00:00:00
abstract::Degenerative diseases are becoming more common with increasing life expectancy of the human population. The 20th century faced a progressive demographic change in the industrialized world, followed by identical trends in population aging in Asia, Africa, and Middle and South America. A significant increase in chronic ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026618666171215094029
更新日期:2017-01-01 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::Prenatal alcohol (ethanol) exposure (PAE) is the underlying cause for a variety of birth defects and neurodevelopmental deficits referred to as "Fetal Alcohol Spectrum Disorders (FASD)". The more visible phenotypes caused by PAE include growth retardation, and characteristic craniofacial abnormalities associated with ...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160414124816
更新日期:2017-01-01 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::In this paper we applied the "macromolecular docking" procedure to perform molecular modeling with the aim of screening transcription factor sequences for possible interaction to the HIV-1 TAR-RNA, employing the software Hex version 4.2. The molecular modeling data were compared with electrophoretic mobility shift ass...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/156802612800166800
更新日期:2012-01-01 00:00:00
abstract::At present, a limited number of strategies exist for diagnostic imaging of patients with bacterial infection. While radiolabeled probes and white blood cells provide robust solutions to detect bacteria in humans, they also give false positives in cases of sterile inflammation. With the onset of bacterial drug resistan...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611313040008
更新日期:2013-01-01 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::The emergence of multi-resistant bacteria to drugs is recognized as a major cause of the increasing number of deaths in hospitals. Killing these bacteria require multiple expensive drugs that can have side effects. Metal nanoparticles may provide a new strategy to combat them. Due the antimicrobial and antiviral prope...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150414141601
更新日期:2015-01-01 00:00:00
abstract::Telomeres are structurally nucleoprotein complexes at termini of linear chromosomes and essential to chromosome stability/integrity. In normal human cells, telomere length erodes progressively with each round of cell divisions, which serves as an important barrier to uncontrolled proliferation and malignant transforma...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026620666200106145340
更新日期:2020-01-01 00:00:00
abstract::It is well established that matrix metalloproteinases (MMPs) contribute to the degradation of the extracellular matrix of coronary plaque and contribute to the thinning of the fibrous cap. As a result, the atheromatous plaque becomes unstable and prone to rupture with consequent clinical manifestations including acute...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026611208011206
更新日期:2012-01-01 00:00:00
abstract::Pulmonary drug delivery represents the best way of treating lung diseases, since it allows direct delivery of the drug to the site of action, with few systemic effects. Meanwhile, the lungs may be used as a portal of entry to the body, allowing systemic delivery of drugs via the airway surfaces into the bloodstream. I...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026615666150108123256
更新日期:2015-01-01 00:00:00
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::Firefly shows bioluminescence by "luciferin-luciferase" (L-L) reaction using luciferin, luciferase, ATP and O2. The chemical photon generation by an enzymatic reaction is widely utilized for analytical methods including biological imaging in the life science fields. To expand photondetecting analyses with firefly biol...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026616666160413130047
更新日期:2016-01-01 00:00:00
abstract::Results of various projects on Mexican Indian ethnobotany and some of the subsequent pharmacological and phytochemical studies are summarised focusing both on chemical-pharmacological as well as anthropological (ethnopharmacological) aspects of our research. We have identified taste and smell properties of medicinal (...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/1568026033392570
更新日期:2003-01-01 00:00:00
abstract::A series of novel derivatives of 1,3-oxazolidin-2-one 12a-12n has been synthesized starting from 4-nitro-(L)- phenylalanine by involving five-step reaction sequence. All the compounds were screened for their in vitro antibacterial activity against four pathogenic bacterial strains namely, Staphylococcus aureus, Bacill...
journal_title:Current topics in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/15680266113139990132
更新日期:2013-08-01 00:00:00