CDK inhibitors in clinical development for the treatment of cancer.


: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.


Fischer PM,Gianella-Borradori A




Has Abstract


2003-06-01 00:00:00












  • Academy for Eating Disorders International Conference on Eating Disorders. Denver, CO, USA, May 29-31, 2003.

    abstract::The focus of this meeting was the interface between eating disorders and obesity. A symposium at this meeting dealt with advances in treatment for bulimia nervosa (BN) and binge eating disorder. There were two presentations in this symposium that addressed pharmacological treatments. One reviewed drug treatments for B...

    journal_title:Expert opinion on investigational drugs



    authors: Kaplan AS

    更新日期:2003-08-01 00:00:00

  • American Association for Cancer Research 1997: progress and new hope in the fight against cancer.

    abstract::Considerable progress has been made with tyrosine kinase inhibitors. After long and sustained efforts, several tyrosine kinase inhibitors with convincing in vivo experimental antitumour properties such as CP-358,774, ZD 1839, CEP-751 are entering Phase I clinical trials. Significant in vivo experimental antitumour act...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章


    authors: Lavelle F

    更新日期:1997-06-01 00:00:00

  • Aromatic diamidines as antiparasitic agents.

    abstract::Parasitic infections are widespread in developing countries and frequently associated with immunocompromised patients in developed countries. Consequently, such infections are responsible for a significant amount of human mortality, morbidity and economic hardship. A growing consensus has identified the urgent need fo...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Soeiro MN,De Souza EM,Stephens CE,Boykin DW

    更新日期:2005-08-01 00:00:00

  • Investigational Janus kinase inhibitors.

    abstract:INTRODUCTION:Dysregulation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is central to the pathophysiology of myeloproliferative neoplasms (MPN). Small molecule inhibitors of JAK family members are currently under investigation for the treatment of MPN. Of these, ruxolitinib ha...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Tam CS,Verstovsek S

    更新日期:2013-06-01 00:00:00

  • Safely slowing down the decline in Alzheimer's disease: gene therapy shows potential.

    abstract::The role of nerve growth factor in stimulating cholinergic function, loss of which is a cardinal feature in Alzheimer's disease, has been documented for many years from preclinical animal model studies. This anabolic growth factor has been delivered into the forebrain of patients with mild Alzheimer's disease using tr...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Braddock M

    更新日期:2005-07-01 00:00:00

  • Urokinase receptor antagonists: novel agents for the treatment of cancer.

    abstract::The interaction between the urokinase receptor (uPAR) and its ligand urokinase (uPA) mediates phenomena such as tissue remodelling, chemotaxis, tumour invasion, dissemination, proliferation, and angiogenesis. The broad-spectrum of biological processes that the uPA/uPAR interaction plays a role in has led researchers t...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章


    authors: Weidle UH,König B

    更新日期:1998-03-01 00:00:00

  • Targeted therapy for haematological malignancies: clinical update from the American Society of Hematology, 2004.

    abstract::Recent advances in the treatment and management of haematological malignancies are due in large part to an improved understanding of the basic biology that drives tumour cell growth and survival. This improved understanding has led to the clinical study and approval of a number of different targeted agents across a nu...

    journal_title:Expert opinion on investigational drugs



    authors: Haas M,Lonial S

    更新日期:2005-09-01 00:00:00

  • Novel C5a regulators in inflammatory disease.

    abstract::Complement is part of the innate immune system, acting to protect the host from microorganisms such as bacteria, and other foreign and abnormal cells. Although primarily protective, complement activation can also cause damage to the host. In a number of inflammatory diseases, including rheumatoid arthritis and dermati...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Mizuno M,Cole DS

    更新日期:2005-07-01 00:00:00

  • Future prospects of anticytokine therapy in chronic heart failure.

    abstract::Several lines of evidence suggest that chronic heart failure is a state of chronic inflammation. Indeed, various pro-inflammatory markers, including the cytokines TNF-alpha, and interleukin 6 and 1, are activated in the course of the disease. In chronic heart failure, these substances are frequently induced even befor...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: von Haehling S,Anker SD

    更新日期:2005-02-01 00:00:00

  • Inhibiting PAR-1 in the prevention and treatment of atherothrombotic events.

    abstract:IMPORTANCE OF THE FIELD:Aspirin, an irreversible inhibitor of thromboxane A(2) production, in combination with clopidogrel, an inhibitor of PY(12) ADP platelet receptors, represents the current standard-of-care of antiplatelet therapy for patients with acute coronary syndrome and those undergoing percutaneous coronary ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Tomasello SD,Angiolillo DJ,Goto S

    更新日期:2010-12-01 00:00:00

  • Clevudine for the treatment of chronic hepatitis B virus infection.

    abstract::Chronic hepatitis B virus (HBV) infection is a major health problem that is responsible for < or = 1 million deaths and 500,000 cases of hepatocellular carcinoma worldwide each year. Drugs that are currently approved by the FDA for the treatment of chronic HBV consist of two groups: the immunomodulators, such as conve...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Hui CK,Lau GK

    更新日期:2005-10-01 00:00:00

  • Pharmacological female contraception: an overview of past and future use.

    abstract::Female hormonal contraceptive methods have undergone slow change over the past four decades. Due to social, political and legal reasons, as well as medical complications, several new methods have been removed from the contraceptive armamentarium almost as quickly as they have been added. With worldwide unintended preg...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Economidis MA,Mishell DR Jr

    更新日期:2005-04-01 00:00:00

  • Skin substitutes to enhance wound healing.

    abstract::Biologically-based skin substitutes have developed as commercial products over the last 5 years. The first generation includes the collagen-based synthetic device, Integra, and Alloderm, which is based on devitalised and cross-linked human dermis. These are used as dermal replacements for third degree burns. Within th...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章


    authors: Mansbridge J

    更新日期:1998-05-01 00:00:00

  • Alpha-lipoic acid, an anti-obesity agent?

    abstract::Obesity shortens life expectancy and is a risk factor for hypertension and Type 2 diabetes. When added to the standard chow of Sprague-Dawley or Otsuka Long-Evans Tokushima Fatty rats, alpha-lipoic acid (0.5% weight/weight) reduced body weight and food intake. Alpha-lipoic acid also increased whole-body energy expendi...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Doggrell SA

    更新日期:2004-12-01 00:00:00

  • IBC's 5th Annual Conference on Blood Substitutes.

    abstract::IBC's 5(th) Annual Conference on Blood Substitutes was held on November 20-21, 1997. Approximately 100 medical researchers, academic scientists, blood substitute company speakers and representatives from major pharmaceutical companies with an interest or partner in the field attended. The papers presented focused on t...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章


    authors: Shorr RG

    更新日期:1998-02-01 00:00:00

  • Inhibiting signal transducer and activator of transcription 3: rationality and rationale design of inhibitors.

    abstract:INTRODUCTION:Signal transducer and activator of transcription 3 (STAT3) controls a key signaling pathway in the development of many malignant diseases. Several genetic studies have proven its central role in the regulation of apoptosis, proliferation, angiogenesis and immune responses making it an attractive target for...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Mankan AK,Greten FR

    更新日期:2011-09-01 00:00:00

  • Anti-epidermal growth factor receptor drugs in cancer therapy.

    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


    authors: Ciardiello F,Tortora G

    更新日期:2002-06-01 00:00:00

  • The therapeutic potential of cationic peptides.

    abstract::Novel classes of antibiotics that are useful against resistant bacteria are a major need in human medicine. Cationic antimicrobial peptides are utilised as nature's antibiotics, being produced constitutively or in response to infection in virtually every type of organism from plants and insects to man. Thus, these pep...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章


    authors: Hancock RE

    更新日期:1998-02-01 00:00:00

  • Experimental therapies targeting apolipoprotein C-III for the treatment of hyperlipidemia - spotlight on volanesorsen.

    abstract:INTRODUCTION:Despite the substantial reduction in cardiovascular morbidity and mortality after the management of dyslipidemia with statins, residual risk remains even after achieving low-density lipoprotein cholesterol targets. This residual risk appears to be partly attributed to low levels of high-density lipoprotein...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Milonas D,Tziomalos K

    更新日期:2019-04-01 00:00:00

  • Investigational agents for the treatment of growth hormone-insensitivity syndrome.

    abstract::Growth hormone-insensitivity syndrome (GHIS) is usually caused by mutations in the growth hormone receptor. Recombinant IGF-I has been used to treat GHIS either alone (mecasermin) or in combination with IGF-binding protein (IGFBP)-3 (mecasermin rinfabate). IGF-I increases the growth velocity of children with IGF defic...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Kemp SF,Thrailkill KM

    更新日期:2006-04-01 00:00:00

  • Discontinued drugs in 2008: oncology drugs.

    abstract::The failure of drug candidates in clinical development remains a critical issue for the pharmaceutical and biotechnology industries. This article documents those oncology drugs discontinued in 2008 and briefly reviews reasons for termination of development. Source information was derived from a search of the Pharmapro...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章


    authors: Williams R

    更新日期:2009-11-01 00:00:00

  • The therapeutic potential of testosterone patches.

    abstract::In the last decade, transdermal delivery of testosterone (T) has been shown to be a safe and effective means of treating male hypogonadism. Transdermal T patches can provide for physiologic androgen replacement in over 90% of men with hypogonadism. In addition, T patches have been shown to be equivalent to im. T ester...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章


    authors: Amory JK,Matsumoto AM

    更新日期:1998-12-01 00:00:00

  • Prinomastat, a hydroxamate-based matrix metalloproteinase inhibitor. A novel pharmacological approach for tissue remodelling-related diseases.

    abstract::Prinomastat (formerly AG3340, Agouron Pharmaceuticals, Inc.) is a potent, selective oral inhibitor of matrix metalloproteinase-2, -9, -13 and -14. This peculiar selectivity should represent an advantage for prinomastat in terms of efficacy/tolerability. The drug has been shown to inhibit tumour growth and angiogenesis...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Scatena R

    更新日期:2000-09-01 00:00:00

  • 57th American Diabetes Association annual meeting.

    abstract::The annual meeting of the American Diabetes Association was held in Boston, MA. There were over 6500 participants, one-third from overseas, and 1103 papers were presented. Abstracts from the meeting have been published, from which abstract numbers are given below, e.g., (A141). Considerable progress has been made in u...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章


    authors: Colca J

    更新日期:1997-08-01 00:00:00

  • Defining and targeting wild-type BRCA high-grade serous ovarian cancer: DNA repair and cell cycle checkpoints.

    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


    authors: Ivy SP,Kunos CA,Arnaldez FI,Kohn EC

    更新日期:2019-09-01 00:00:00

  • The therapeutic potential of PD156707 and related butenolide endothelin antagonists.

    abstract::Plasma concentrations of the peptide endothelin (ET) are elevated in several cardiovascular diseases. Animal studies suggest that activation of ET receptors may contribute to the increase in vascular resistance and remodelling of cardiovascular tissues that are characteristic of these pathologies. Antagonists of these...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章


    authors: Maguire JJ,Davenport AP

    更新日期:1999-01-01 00:00:00

  • The therapeutic potential of phytoestrogens.

    abstract::Phytoestrogens, such as the soya isoflavones genistein and daidzein, are currently being extensively investigated through both molecular, preclinical and clinical studies to determine their potential health benefits. Phytoestrogens may protect against chronic diseases such as hormone-dependent cancer (e.g., breast and...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Wiseman H

    更新日期:2000-08-01 00:00:00

  • VEGF inhibitors for the treatment of neovascular age-related macular degeneration.

    abstract::Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world for those patients aged 50 years or older. Neovascular AMD, a subtype characterized by the growth of new, pathologic blood vessels, results in most of the cases of severe and rapid vision loss associated with AMD. A critical ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Barakat MR,Kaiser PK

    更新日期:2009-05-01 00:00:00

  • Investigations on gossypol: past and present developments.

    abstract::Gossypol has received significant attention as a result of its potential therapeutic application as a male antifertility agent. Furthermore, recent research examining the biological activity of gossypol has revealed a number of other promising lines of enquiry. These have focused on the antitumour, antiviral and antio...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Dodou K,Anderson RJ,Small DA,Groundwater PW

    更新日期:2005-11-01 00:00:00

  • Polidocanol for endovenous microfoam sclerosant therapy.

    abstract:BACKGROUND:Polidocanol is a liquid surfactant having endothelial cell lytic properties. In the form of a controlled, dispensed microfoam it is administered endovenously as a sclerosing agent in the treatment of varicose veins. OBJECTIVE:This review summarizes efficacy of polidocanol endovenous microfoam sclerotherapy ...

    journal_title:Expert opinion on investigational drugs

    pub_type: 杂志文章,评审


    authors: Eckmann DM

    更新日期:2009-12-01 00:00:00