Abstract:
:Cathepsin K, a cysteine protease of the papain family, was identified by sequencing complementary DNA libraries derived from osteoclasts. Cathepsin K can cleave bone proteins such as Type I collagen, osteopontin, and osteonectin. The localization and maturation of cathepsin K in activated osteoclasts have been characterized. Furthermore, mutation of the gene expressing cathepsin K in humans results in pycnodysostosis, an autosomal recessive condition, resulting in osteoprosis and increased bone fragility. Knockout of cathepsin K in the mouse also results in retarded bone matrix degradation and osteopetrosis. Together, these data demonstrate that inhibition of cathepsin K should result in a dimunition of osteoclast-mediated bone resorption. Several novel classes of cathepsin K inhibitors have been designed from X-ray co-crystal structures of peptide aldehydes bound to papain. The convergence of the design of novel inhibitors and the discovery of cathepsin K has created opportunities to further understand bone and cartilage biology as well as provide new therapeutic agents for the treatment of disease states in man such as osteoporosis.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Yamashita DS,Dodds RAdoi
10.2174/1381612003401569subject
Has Abstractpub_date
2000-01-01 00:00:00pages
1-24issue
1eissn
1381-6128issn
1873-4286journal_volume
6pub_type
杂志文章,评审abstract::Type 2 diabetes is associated with substantially increased cardiovascular mortality. The need to reduce the progression of atherosclerosis alongside lowering blood glucose levels is now well established. Ideally, pharmaceutical treatment should address both of these needs. This review summarises current evidence of th...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789057995
更新日期:2009-01-01 00:00:00
abstract::In patients with acute coronary syndromes (ACS), hypertension is common. The type of ACS and severity of hypertension would determine the treatment algorithm. In ST elevation myocardial infarction (MI), time to reperfusion is essential whereas in malignant hypertension the reduction of blood pressure to prevent end or...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781663046
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Buccal delivery is an alluring course of organization for fundamental medication conveyance and it leads direct access to the systemic flow through the interior jugular vein sidesteps drugs from the hepatic first-pass digestion gives high bioavailability. OBJECTIVE:This article aims at buccal medication con...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200614182013
更新日期:2020-01-01 00:00:00
abstract::The phenomenon of blood serum atherogenicity was described as the ability of human serum to induce lipid accumulation in cultured cells. The results of recent two-year prospective study in asymptomatic men provided the evidence for association between the changes in serum atherogenicity and dynamics of carotid intima-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612820666140212194614
更新日期:2014-01-01 00:00:00
abstract::Fibrate derivatives have a 40-year history in the management of dyslipidemia. Although this class of drugs is generally well tolerated, several safety issues have arisen from their use. In the present article we review the literature describing side effects associated with the use of fibrates except for those that are...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208783885362
更新日期:2008-01-01 00:00:00
abstract::Exercise and sports activity are beneficial both physically and psychologically but excessive exercise may have adverse physiological and psychological effects. There are methodological issues in the definition, diagnosis and etiology of exercise addiction. Several questionnaires and diagnostic tools have been develop...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990614
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170809115429
更新日期:2017-01-01 00:00:00
abstract::We set up two models of gastric bleeding in rats using low-dose aspirin (ASA) and the antiplatelet drug clopidogrel, a P2Y₁₂ receptor antagonist, and examined the effect of antiulcer drugs on gastric bleeding and ulcerogenic responses under such conditions. Under urethane anesthesia, two catheters were inserted into t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990418
更新日期:2014-01-01 00:00:00
abstract::This review presents a comprehensive attempt to conclude and discuss various glucose biosensors based on core@shell magnetic nanomaterials. Owing to good biocompatibility and stability, the core@shell magnetic nanomaterials have found widespread applications in many fields and draw extensive attention. Most magnetic n...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150917092528
更新日期:2015-01-01 00:00:00
abstract::Drug development for neurodegenerative diseases such as Alzheimer's disease (AD) is a challenge, not only due to the cellular molecular mechanisms involved, but also because of the inherent difficulty of most molecules to cross the blood-brain-barrier (BBB). A promising approach to overcome these drawbacks is developi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150130120358
更新日期:2015-01-01 00:00:00
abstract::The antifungal agents for systemic mycoses are only a few in number. Among them amphotericin-B is still the most widely used drug, but substantial side effects including nephrotoxicity limits its clinical usefulness. Efforts to lower the toxicity are synthesis of AMPH-B analogues such as AMPH-B esters and encapsulatio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023395916
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:There are controversial results available about using angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) and the development of cancers or improvement of clinical outcomes. Studies reported that using ACEI/ARB may enhance the development of hepatocellular carcinoma (HCC...
journal_title:Current pharmaceutical design
pub_type: meta分析
doi:10.2174/1381612826666200713165018
更新日期:2020-01-01 00:00:00
abstract::Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20% to 30% of patients. The current approach is to make a firm diagnosis, give combination antibiotic and antisecretory therapy, and confirm...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399077
更新日期:2000-10-01 00:00:00
abstract::Protection of the brain is strengthened by active transport and ABC transporters. P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a substrate from the brain, which is important for maintaining loco-regional homeostasis in the brain and protection against toxic com...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211797440122
更新日期:2011-01-01 00:00:00
abstract::Marine invertebrates, especially tunicates, are a lucrative resource for the discovery of new lead compounds for the development of clinically utilized drugs. This review describes the isolation, synthesis and biological activities of several classes of marine-derived butenolide natural products, namely rubrolides and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200518110617
更新日期:2020-01-01 00:00:00
abstract::Iron oxide (Fe₃O₄) nanoparticles (IONPs) have received much attention for their utility in biomedical applications such as magnetic resonance imaging, drug delivery and hyperthermia. Recent studies reported that IONPs induced cytotoxicity in mammalian cells. However, little is known about the genotoxicity of IONPs fol...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612811319370011
更新日期:2013-01-01 00:00:00
abstract::Mass spectrometry imaging (MSI) can uniquely detect thousands of compounds allowing both their identification and localization within biological tissue samples. MSI is an interdisciplinary science that crosses the borders of physics, chemistry and biology, and enables local molecular analysis at a broad range of lengt...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170111112550
更新日期:2017-01-01 00:00:00
abstract::Drug hypersensitivity reactions (DHRs) represent a major burden on the healthcare system since their diagnostic and management are complex. As they can be influenced by individual genetic background, it is conceivable that the identification of variants in genes potentially involved could be used in genetic testing fo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666191105122414
更新日期:2019-01-01 00:00:00
abstract::Since the discovery of human immunodeficiency virus (HIV) as a causative agent of acquired immune deficiency syndrome (AIDS) various strategies were employed to counter its devastating actions. One such concept relies on the prevention of HIV entry into host's "competent" cells by means of compounds known as entry inh...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319100003
更新日期:2013-01-01 00:00:00
abstract::Asthma is an allergic disease that affects approximately 300 million people worldwide. Two of its phenotypes routinely assessed at the clinic include airway hyperresponsiveness and IgE production. They can be measured in a non-invasive manner and have been used for genetic studies. The genetic complexity of asthma and...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160829141708
更新日期:2016-01-01 00:00:00
abstract::Hepatitis C virus (HCV) infects an estimated 170 million people globally and persistent infection within the liver is the usual outcome of infection. The resulting liver disease leads to substantial morbidity and to date no vaccine exists. Furthermore the treatments available are frequently ineffective. A minority of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784746806
更新日期:2008-01-01 00:00:00
abstract::Angiogenesis is regulated by stimulators and inhibitors and involve multiple biological processes including endothelial cell proliferation, migration, cell-cell and cell-matrix adhesion, assembly into tube structures as well as apoptosis. Designing and developing peptides for therapeutic application to inhibit angioge...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161207781039715
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:The use of essential oils is receiving increasing attention worldwide, as these oils are good sources of several bioactive compounds. Nowadays essential oils are preferred over synthetic preservatives thanks to their antioxidant and antimicrobial properties. Several studies highlight the beneficial effect of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200121092018
更新日期:2020-01-01 00:00:00
abstract::The complete DNA sequence of the human genome and of several related mammals are now available, due to the investments of enormous resources and advances in sequencing technology. Novel technologies have been developed to compare multiple genomes with each other, thus specifying regions of sequence similarity among ma...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778559795
更新日期:2006-01-01 00:00:00
abstract::ADAM (a disintegrin and metalloproteinase) proteins have a predominant role in the protein ectodomain shedding of membrane-bound molecules. ADAMs have emerged as critical regulators of cell-cell signaling during development and homeostasis, and are believed to contribute to pathologies, such as cancer, where their reg...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788682415
更新日期:2009-01-01 00:00:00
abstract::There is a high rate of benzodiazepine use in the population. Benzodiazepines are used for multiple indications (anxiety, seizures, alcohol withdrawal, muscular relaxation and anesthesia). Benzodiazepines are also addictive substances and a non-negligible fraction of regular users will develop dependence. There is cur...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150619092039
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Mitochondria are cellular organelles responsible for energy production, calcium handling, controlled synthesis of reactive oxygen species (ROS), and regulation of apoptosis. All these functions are crucial for cardiac homeostasis, and may be impaired in chronic heart failure (CHF). Therefore, mitochondrial d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160701075027
更新日期:2016-01-01 00:00:00
abstract::Microdialysis is a technique for sampling the chemistry of the interstitial fluid of tissues and organs in animal and man. It is minimally invasive and simple to perform in a clinical setting. Although microdialysis samples essentially all small molecular substances present in the interstitial fluid the use of microdi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384105
更新日期:2004-01-01 00:00:00
abstract::Kv7.x channels are a family of six transmembrane domain, single pore-loop, voltage-gated K(+) channels. Five members of the family have been identified to date, including the cardiac channel Kv7.1 (formerly known as KvLQT1) and four neuronal Kv7.x channels, Kv7.2-5. Heteromeric channels containing Kv7.3 and either Kv7...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788186326
更新日期:2009-01-01 00:00:00
abstract::Psoriasis is an immune-mediated, chronic and recurrent inflammatory skin disease, prevalent worldwide, and represents an important burden in life quality of patients. The most common clinical variant is termed as psoriasis vulgaris or plaque psoriasis, which with an individualized and carefully monitored therapy can d...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190618122024
更新日期:2019-01-01 00:00:00