Abstract:
:Cyclin-dependent protein kinases (CDKs) are key regulators of the cell division cycle, whose various checkpoints proliferating cells must traverse. Since CDK deregulation, either through direct or indirect means, is found in most cancer cells, pharmacological CDK inhibition has become an attractive strategy towards mechanism-based and non-genotoxic therapies in oncology. Over the last decade, discovery and lead optimisation efforts have provided a wealth of potential drug candidate molecules capable of inhibiting CDKs, blocking cell-cycle progression, modulating transcription and inducing apoptosis selectively in cancer cells. However, only few such agents have as yet reached clinical evaluation. Here, the preclinical and clinical results obtained so far with flavopiridol (L868275, HMR1275; Aventis), 7-hydroxystaurosporine (UCN-01, KW-2401; Kyowa Hakko Kogyo) and roscovitine (R-roscovitine, CYC202; Cyclacel) are summarised. Furthermore, the potential for monotherapy and applications in combination with existing drugs are discussed.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Fischer PM,Gianella-Borradori Adoi
10.1517/13543784.12.6.955subject
Has Abstractpub_date
2003-06-01 00:00:00pages
955-70issue
6eissn
1354-3784issn
1744-7658journal_volume
12pub_type
杂志文章,评审abstract:INTRODUCTION:Recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis. With the emergence of monoclonal antibodies and tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR), several drugs were developed and tested in HNSCC. To date, the monoclonal...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1177022
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:Hematopoietic stem cell (HSC) transplantation is a treatment option for hematological malignancies. Current mobilization regimes frequently result in inadequate numbers of HSC for transplant therefore alternative methods of mobilization are required. OBJECTIVE:The chemokine receptor CXCR4 and ligand SDF-1 a...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.11.1749
更新日期:2008-11-01 00:00:00
abstract:INTRODUCTION:In the last decade, concerns have been raised around the use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in chronic kidney disease (CKD) patients, especially when given at high doses. Moreover, treatment with ESA is expensive. AREAS COVERED:We searched PubMed for original articles, re...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1493455
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND:Interferon-alpha (IFN-α) is the traditional therapeutic agent for chronic myeloid leukemia (CML). The molecular mechanism of IFN-α efficacy in the treatment of CML is not fully clear. OBJECTIVES:To identify the peptides and/or proteins that bind to the proteins specifically expressed on the surface of IFN-α...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.2011.632407
更新日期:2011-12-01 00:00:00
abstract:INTRODUCTION:Progesterone receptor (PR) agonists (progestins) and antagonists are developed for female contraceptives. However, non-contraceptive applications of newer progestins and PR modulators are being given more attention. AREAS COVERED:The newer PR agonists including drospirenone, nomegestrol, trimegestone, die...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.642368
更新日期:2012-01-01 00:00:00
abstract:INTRODUCTION:Compounds that inhibit or modulate γ-secretase, the pivotal enzyme which generates β-amyloid (Aβ), are potential therapeutics for Alzheimer's disease (AD). AREAS COVERED:This article briefly reviews the profile of γ-secretase inhibitors that have reached the clinic and discusses the clinical issues surrou...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.550572
更新日期:2011-03-01 00:00:00
abstract:BACKGROUND:Age-related macular degeneration is the leading cause of blindness among elderly individuals in industrialized countries. New drugs and advanced concepts for the treatment of dry AMD (dAMD) are needed. A new approach is the application of intravenous infusions of prostaglandin E1. OBJECTIVE:The aim of this ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1517/13543784.2013.794782
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Armodafinil is a wake-promoting agent developed by Cephalon that was approved in mid-2007 for the treatment of excessive sleepiness associated with narcolepsy, obstructive sleep apnea and shift work disorder. It is the R-enantiomer of the compound modafinil. Like modafinil, the mechanism of action for armoda...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.4.565
更新日期:2008-04-01 00:00:00
abstract::Preclinical studies suggest that the brain corticotropin-releasing factor (CRF) systems mediate anxiety-like behavioural and somatic responses through actions at the CRF1 receptor. CRF1 antagonists block the anxiogenic-like effects of CRF and stress in animal models. Cerebrospinal fluid levels of CRF are elevated in s...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.13.7.799
更新日期:2004-07-01 00:00:00
abstract:INTRODUCTION:In asthma, most commonly, 'conventional' anti-inflammatory medications represented by inhaled corticosteroids and leukotriene inhibitors are effective. In some patients however additional inhibition of the airways inflammation is necessary. Such compounds might be molecules inhibiting specifically certain ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1227319
更新日期:2016-10-01 00:00:00
abstract::Diabetes is a chronic, debilitating disease that afflicts millions of people worldwide and poor glycemic control in this disease leads to numerous microvascular and macrovascular complications. There is growing evidence that tight glycemic control prevents the development, and delays the progression, of microvascular ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.10.1673
更新日期:2007-10-01 00:00:00
abstract:BACKGROUND:Potent new drugs against multidrug-resistant Gram-negative bacteria, namely Pseudomonas aeruginosa and Acinetobacter spp. and pan-drug-resistant Klebsiella pneumoniae, which constitute an increasing medical threat, are almost absent from the future pharmaceutical pipeline. OBJECTIVE:This drug evaluation foc...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.5.749
更新日期:2008-05-01 00:00:00
abstract:INTRODUCTION:Although significant advances have been made in the treatment of advanced renal cell carcinoma (RCC), patients still develop resistance to standard therapies and require the administration of subsequent lines of treatment. New therapeutic approaches are thus imperative to improve the prognosis for patients...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2018.1427731
更新日期:2018-02-01 00:00:00
abstract::The epidermal growth factor receptor is a cell membrane growth factor receptor that plays a key role in cancer development and progression. Epidermal growth factor receptor-activated signalling pathways control cell proliferation, apoptosis, angiogenesis and metastatic spread in the majority of human epithelial cancer...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.6.755
更新日期:2002-06-01 00:00:00
abstract::'Male factor' problems contribute to subfertility in a significant proportion of couples. In some instances, defective sperm production has qualitative and/or quantitative effects on the semen profile; in others, no obvious defects can be detected, yet spermatozoa are non-fertilising. Recent studies have revealed that...
journal_title:Expert opinion on investigational drugs
pub_type: 社论
doi:10.1517/13543784.6.12.1797
更新日期:1997-12-01 00:00:00
abstract:INTRODUCTION:Myocardial fibrosis is a remarkably dynamic process mediated by different molecular pathways that represent potential targets of novel therapeutic interventions. Transforming Growth Factor-beta (TGF-β), connective Tissue Growth Factor (cTGF) and Galectin-3 (Gal-3) represent the most promising targets on wh...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2021.1868432
更新日期:2021-01-04 00:00:00
abstract:INTRODUCTION:Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are the two complications of diabetes that cause visual loss and blindness. Laser photo-coagulation in the past was used to prevent progression of disease to these advanced stages. Advances in pathophysiologic understanding of DME an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1201062
更新日期:2016-09-01 00:00:00
abstract::Introduction: Cyclin-dependent kinase 7 (CDK7) is a part of the CDK-activating kinase family (CAK) which has a key role in the cell cycle and transcriptional regulation. Several lines of evidence suggest that CDK7 is a promising therapeutic target for cancer. CDK7 selective inhibitors such as SY-5609 and CT7001 are in...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2021.1850693
更新日期:2021-01-01 00:00:00
abstract::Advances in molecular medicine have revealed a key role for altered gene expression in the aetiology of many inflammatory diseases, including asthma, rheumatoid arthritis, inflammatory bowel disease and sepsis. Until recently, however, modulation of gene transcription has not been the subject of directed pharmaceutica...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.5.555
更新日期:1997-05-01 00:00:00
abstract:INTRODUCTION:Sorafenib is an oral multikinase inhibitor with anti-angiogenic and anti-proliferative activity that is indicated for use in hepatocellular and renal cell carcinomas. Sorafenib is being developed in a number of solid tumors, including breast cancer (BC). AREAS COVERED:A series of four randomized, double-b...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.689824
更新日期:2012-08-01 00:00:00
abstract::COPD is a chronic disease of the lung that is characterised by decreased air flow and associated abnormal inflammatory responses of the lungs. A total of 80% of COPD incidences are observed in patients with history of smoking tobacco. The chronic condition of COPD is characterised by airway remodelling, which leads to...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.7.1069
更新日期:2007-07-01 00:00:00
abstract:INTRODUCTION:Aberrant regulation of platelet-derived growth factors (PDGFs) and their receptors (PDGFR) has been shown to be involved in many solid tumors, including breast cancer. PDGFR-α and PDGFR-β expressions were documented in breast cancer and are correlated with tumor aggressiveness and metastasis. Preclinical e...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2014.895323
更新日期:2014-05-01 00:00:00
abstract::The discovery of new antibacterial drugs can be based either upon empirical screening methods or structure-based design. Empirical methods utilise both intact bacteria and isolated biochemical targets for high throughput screening of natural product or chemical libraries to detect inhibitor leads. Structure-based meth...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.8.1019
更新日期:1997-08-01 00:00:00
abstract::The increasing frequency of fungal infections in immunocompromised patients together with the emergence of strains resistant to currently used antifungal drugs point to an increased need for a new class of antimycotics. Antimicrobial peptides are promising candidates for the treatment of fungal infections since they h...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.2.309
更新日期:2002-02-01 00:00:00
abstract::Introduction: Molecular analyzes including molecular descriptor/phenotype interactions have led to better characterization of epithelial ovarian cancer patients, including a definition of a BRCA wild-type (BRCAwt) phenotype. Understanding how and when to use agents targeted against dependent BRCAwt pathways or other m...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2019.1657403
更新日期:2019-09-01 00:00:00
abstract::CGRP is a potent vasodilator that has been shown to have a physiological and/or pathological role in neurogenic inflammation, headaches including migraine, thermal injury, circulatory shock, pregnancy and menopause, hypertension and heart failure and is known to be cardioprotective. CGRP is also a positive inotrope an...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.6.1131
更新日期:2001-06-01 00:00:00
abstract:INTRODUCTION:Although the combination of an anti-CD20 monoclonal antibody and chemotherapy has widely improved survival of patients with B-cell lymphoma, the disease still relapses. A better understanding of the biology of lymphomas has highlighted the role of the cell of origin in response to treatment and outcome. Le...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2016.1208170
更新日期:2016-09-01 00:00:00
abstract::Risperidone (Risperdal) is a benzisoxazole derivative with a high affinity for serotonin 5-HT2 and dopamine D2 receptors, and some affinity for alpha- adrenergic, histamine H1 and dopamine D1 receptors. It has no anticholinergic effects. Early studies demonstrated risperidone to be an effective medication for psychoti...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.8.4.443
更新日期:1999-04-01 00:00:00
abstract::Gaucher disease (GD) is an inborn error of glycosphingolipid metabolism, associated with multisystemic manifestations resulting from the lysosomal accumulation of an incompletely degraded material (glucosylceramide) within cells of monocyte/macrophage lineage. In the majority of GD patients with non-neurological invol...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.2.273
更新日期:2003-02-01 00:00:00
abstract::Introduction: Plasma kallikrein is a mediator of vascular leakage and inflammation. Activation of plasma kallikrein can induce features of diabetic macular edema (DME) in preclinical models. Human vitreous shows elevated plasma kallikrein levels in patients with DME. Because of the incomplete response of some patient...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2020.1723078
更新日期:2020-03-01 00:00:00