Abstract:
:Osteogenic peptides are, or have potential to be, therapies for the treatment of osteoporosis, fracture repair, and repair of loosened bone implants. Human parathyroid hormone has been approved for the treatment of post-menopausal osteoporosis. Constrained analogs of PTH and the parathyroid-hormone related peptide (PTHrP) have aided the understanding of how PTH and PTHrP bind to their common receptor and some of these analogs have improved properties that make them possible candidates for clinical trial. Cyclization by lactam formation has shown that a core region of human PTH (hPTH) from residues 16-26 binds as an alpha-helix to the receptor and that the biological effects are remarkably sensitive to ring size. Appropriate cyclization in this region of the molecule not only has yielded analogs with improved receptor activation but also ones less susceptible to protease degradation and thus more active in vivo. Cyclization has been less successful in the N-terminus region, residues 1-12, of hPTH(1-34) with only a cyclization between residues 6 and 10 showing some promise. The growing understanding of how this region binds to the receptor will lead to other productive constraints. This review also covers the potential of a different class of molecule, the osteogenic growth peptide (OPG), as an anabolic bone agent. These molecules have much weaker anabolic effects than PTH and cyclization does not result in improved activity. However, the information gained from these studies may yield analogs with better pharmacological profiles.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Willick GE,Morley P,Whitfield JFdoi
10.2174/0929867043364153subject
Has Abstractpub_date
2004-11-01 00:00:00pages
2867-81issue
21eissn
0929-8673issn
1875-533Xjournal_volume
11pub_type
杂志文章,评审abstract::Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder characterized by irreversible chronic inflammation and airflow obstruction. It affects more than 64 million patients worldwide and it is predicted to become the third cause of death in the industrialized world by 2030. Currently availab...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180320120054
更新日期:2019-01-01 00:00:00
abstract::Diabetic patients have a two- to four-fold increased risk for the development of microvascular (renal, neuronal and retinal) and macrovascular complications. Unfortunately, these complications may develop in both Type 1 and Type 2 diabetic patients even with careful glycaemic, blood pressure and lipid control. With th...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986706777452515
更新日期:2006-01-01 00:00:00
abstract::For many years the spotlight in drug discovery has been on a relatively small number of validated therapeutic target classes, such as G-protein coupled receptors and enzymes such as protein kinases, with well characterized enzymatic and cellular activities. However, with recent progress in genomics and proteomics, pro...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311320240003
更新日期:2013-01-01 00:00:00
abstract::Chymase stored in mast cells activates matrix metalloproteinase (MMP)-9, which may relate to the progression of sinusoidal obstruction syndrome (SOS). We investigated the preventive effect of a chymase inhibitor, TY-51469, on monocrotaline-induced SOS in hamsters. Hamsters were orally administrated with a single dose ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867311320210008
更新日期:2013-01-01 00:00:00
abstract::Leukoaraiosis (LA), one of the most frequent causes of cognitive disturbances, is presumed to involve vascular demyelinization and cerebral small-vessel diseases. Although it has been suggested that the development of LA is associated with cerebral circulatory disturbances, the pathomechanism of this circulatory probl...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707780362907
更新日期:2007-01-01 00:00:00
abstract::The synthesis and biological evaluation of carbohydrate mimetics has begun to more clearly define the diverse roles of carbohydrates in nature. Often the strategy invoves the design and synthesis of glycosyltransferase and glycosidase inhibitors both as tools to elucidate the mechanism of action of these enzymes and a...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:1999-02-01 00:00:00
abstract::The oxime formation reaction of therapeutical progestogen (levonorgestrel, levonorgestrel acetate, norethisterone), androgen (methyltestosterone, testosterone phenylpropionate) and anabolic (nortestosterone phenylpropionate) Delta(4)-3-ketosteroids has been investigated. The ketosteroid-hydroxylamine reaction was moni...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867013372238
更新日期:2001-09-01 00:00:00
abstract::Pentacyclic triterpenoids including the oleanane, ursane and lupane groups are widely distributed in many medicinal plants, such as Glycyrrhiza species, Gymnema species, Centella asiatica, Camellia sinensis, Crataegus species and Olea europaea, which are commonly used in traditional medicine for the treatment of diabe...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract:: ...
journal_title:Current medicinal chemistry
pub_type: 社论
doi:10.2174/092986732608190516092613
更新日期:2019-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a complex and progressive neurodegenerative disorder. The available therapy is limited to the symptomatic treatment and its efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the development of an effective therapy is crucial for public ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867321666141106122628
更新日期:2015-01-01 00:00:00
abstract::Stress or heat shock proteins (Hsps) Hsp90, Hsp70 and Hsp27 are chaperones that assist the proteins in their folding, stability, assembly into multi-protein complexes and transport across cellular membranes. The expression of some of them is highly induced in response to a wide variety of physiological and environment...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986707782360079
更新日期:2007-01-01 00:00:00
abstract::Nitric oxide (NO) has been established as an important messenger molecule in various steps of brain physiology, from development to synaptic plasticity, learning and memory. However, NO has also been viewed as a major agent of neuropathology when, escaping controlled production it may directly or indirectly promote ox...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033456792
更新日期:2003-10-01 00:00:00
abstract:BACKGROUND:Chronic, degenerative diseases are often characterized by inflammation and aberrant angiogenesis. For these pathologies, including rheumatoid arthritis, cardiovascular and autoimmune diseases, cancer, diabetes, and obesity, current therapies have limited efficacy. OBJECTIVES:The validation of novel (chemo)p...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170920144130
更新日期:2019-01-01 00:00:00
abstract::This review summarizes our knowledge of biochemical, biological and medical applications and properties of phosphinic acid compounds. Phosphinic acid compounds (phosphinates) are derivatives of phosphinic acid H2P(O)(OH). The major attention of this article is focused on applications of phosphinates of a pseudopeptide...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867003374831
更新日期:2000-06-01 00:00:00
abstract::Deregulation of kinase function has been implicated in several important diseases, including cancer, neurological and metabolic disorders. Because of their key role in causing disease, kinases have become one of the most intensively pursued classes of drug targets. To date, several monoclonal antibodies (mAbs) and sma...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986711797189592
更新日期:2011-01-01 00:00:00
abstract::Bicarbonate (HCO₃⁻) membrane transport systems are crucial players in the physiology of several tissues. The molecular basis of HCO₃⁻ membrane transport is of major physiological relevance since this ion is involved in the establishment of intracellular and extracellular ionic composition, osmolariy and pH. The membra...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/15672050113109990200
更新日期:2013-01-01 00:00:00
abstract::Drug repositioning is a strategy to identify new uses for approved or investigational drugs that are used off-label outside the scope of the original medical indication. In this review we report the most relevant studies about drug repositioning in hematology, reporting the signalling pathways and molecular targets of...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867327999200817102154
更新日期:2020-08-16 00:00:00
abstract::Antisynthetase syndrome is a group of closely related rare diseases which clinically manifest with inflammatory myopathies, interstitial lung disease, inflammatory arthritis, skin hyperkeratosis (mechanic’s hands) and Raynaud phenomenon. The pathophysiology of antisynthetase syndrome is not entirely understood, but ge...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:
更新日期:2015-05-13 00:00:00
abstract::Breast cancer is an example of a solid tumour which is well treated in the early stages of disease by surgical excision, but once metastatic spread has occurred, medical therapies (chemotherapy and radiotherapy) are highly toxic, expensive and palliative. It is known that certain tumours exhibit specific patterns of m...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867033457944
更新日期:2003-04-01 00:00:00
abstract::Angiotensin converting enzyme (ACE) 2 is a homologue of ACE that catalyzes the conversion of Angiotensin (Ang) II into Ang1-7, which induces vasodilation, anti-fibrotic, anti-proliferative and anti-inflammatory effects. Given that ACE2 counterbalances the effects of Ang II, it has been proposed as a biomarker in kidne...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170414162841
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Metabolic disorders comprise a set of different disorders varying from epidemic diseases such as diabetes mellitus to inborn metabolic orphan diseases such as phenylketonuria. Despite considerable evidence showing the importance of the computational methods in discovery and development of new pharmaceuticals...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666171002120647
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Vaccines are very effective medical tools for disease prevention and life span increase. Controversies have raised concern about their safety, from autism to polio vaccine contamination with simian virus 40 (SV-40). Hysteria surrounding vaccine-associated risks has resulted in a declining number of vaccinati...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180518072730
更新日期:2018-01-01 00:00:00
abstract::Breast cancer arises in about 48% of patients older than 65 years and more than 30% occurs in those over 70 years being the leading cause of cancer-related death in women older than 65. Elderly patients tolerate chemotherapy poorly compared to their younger counterpart because of progressive reduction of organ functio...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867053363261
更新日期:2005-01-01 00:00:00
abstract::Since its discovery in 1995 adiponectin has garnered considerable interest from the academic, clinical and biotech communities due to its proposed salutary anti-inflammatory, anti-diabetic, anti-atherogenic and cardioprotective properties. As a result our appreciation of adiponectin's structure and the importance of p...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986712803833155
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:The large increase in epidemiological studies on night shift work is due to the important effects of night shift work on workers' health and psychophysical wellbeing. The short-term effects-insomnia, difficulties in managing work and private life, lower work performance, and more work and extra-work accident...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170720160632
更新日期:2019-01-01 00:00:00
abstract::Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases. Enhanced matrix metalloproteinase-2 (MMP-2; gelatinase A) activity has been correlated to c...
journal_title:Current medicinal chemistry
pub_type: 杂志文章
doi:10.2174/0929867013373660
更新日期:2001-02-01 00:00:00
abstract::Developing suitable medicines for genetic diseases requires a detailed understanding of not only the pathways that cause the disease, but also the identification of the genetic components involved in disease manifestation. This article focuses on the complexities associated with ocular ciliopathies - a class of debili...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180917102557
更新日期:2019-01-01 00:00:00
abstract::The focus of this review is the cellular internalisation mechanism of nanostructured systems (NSs) and their endosomal escape for targeted drug delivery. Endocytosis is a cellular process of internalisation of different molecules and foreign microorganisms. It is currently being studied for drug delivery through nanos...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867324666170214111205
更新日期:2017-01-01 00:00:00
abstract::Infections with Mycobacterium tuberculosis, the causative agent of tuberculosis, are difficult to treat using currently available chemotherapeutics. Clinicians agree on the urgent need for novel drugs to treat tuberculosis. In this mini review, we summarize data that prompts the consideration of DNA repair-associated ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867325666180129093546
更新日期:2019-01-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are zinc-endopeptidases responsible for degradation of the extracellular matrix (ECM) components including basement membrane collagen, interstitial collagen, fibronectin, and various proteoglycans, during normal remodeling and repair processes. The turnover and remodeling of ECM must b...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/092986709787846587
更新日期:2009-01-01 00:00:00