Abstract:
IMPORTANCE OF THE FIELD:The evolution of targeted therapies is dependent upon identification of cellular moieties that can be pharmacologically modulated. As one such example, the serine-threonine kinase Akt was identified nearly two decades ago. Since then, its role in mediating multiple signaling cascades (ultimately leading to cell growth and proliferation) has since been identified. More recently, several agents have been developed that antagonize Akt--these agents are in various stages of clinical testing. AREAS COVERED IN THIS REVIEW:Herein, we outline development of several promising Akt inhibitors, including perifosine, MK-2206, RX-0201, PBI-05204, GSK2141795 and others. WHAT THE READER WILL GAIN:The reader will gain insight into the current pipeline of Akt inhibitors, and the degree to which these agents have been examined both clinically and preclinically. TAKE HOME MESSAGE:With an emerging pipeline of agents targeting Akt, it will be critical to decipher which amongst them holds the greatest promise. Herein, we explore this drug pipeline and provide strategies for determining the future clinical application of these agents.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Pal SK,Reckamp K,Yu H,Figlin RAdoi
10.1517/13543784.2010.520701subject
Has Abstractpub_date
2010-11-01 00:00:00pages
1355-66issue
11eissn
1354-3784issn
1744-7658journal_volume
19pub_type
杂志文章,评审abstract::The Kunitz-type proteinase inhibitor, tissue factor pathway inhibitor (TFPI), is the only endogenous inhibitor of the tissue factor (TF)-mediated coagulation pathway that plays a dominant role in normal haemostasis. TFPI exerts its action by binding to factor Xa (FXa) forming a TFPI-FXa complex that then, in a second ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.7.7.1121
更新日期:1998-07-01 00:00:00
abstract::Recent landmark studies using hydroxy-methyl-glutaryl-Co-enzyme A reductase inhibitors (HMG-CoA reductase inhibitors or statins), specifically, pravastatin and simvastatin, have led to dramatic changes in medical practice. These clinical trials have demonstrated that clinicians can impact coronary morbidity and mortal...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.1.31
更新日期:1997-01-01 00:00:00
abstract::Carvedilol is a beta-blocker with ancillary properties. Pilot clinical studies with carvedilol, added to the standard therapy of digoxin, diuretics and ACE inhibitors, showed beneficial effects in mild, moderate and severe heart failure. Patients consistently showed improvement in LV ejection fraction and NYHA functio...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.10.5.971
更新日期:2001-05-01 00:00:00
abstract:INTRODUCTION:Due to improvements in our understanding of the pathogenesis of systemic lupus erythematosus (SLE), several target drugs have been and are being developed. One of the possible targets in SLE is co-stimulation between antigen-presenting cells and T cells. Abatacept is a co-stimulation moderator approved for...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2016.1154943
更新日期:2016-01-01 00:00:00
abstract::Heat shock proteins are vital to cell survival under conditions of stress. They bind client proteins to assist in protein stabilization, translocation of polypeptides across cell membranes and recovery of proteins from aggregates. Heat shock protein inhibitors are a diverse group of novel agents that have been demonst...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903158934
更新日期:2009-09-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Molecules isolated from animals, insects, plants or microorganisms can provide prototypes for design of biopharmaceutical products. Some venom toxins and their derivatives are used in medicine, while others provide templates for development of new drugs. AREAS COVERED IN THIS REVIEW:The mild to...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.534457
更新日期:2010-12-01 00:00:00
abstract:INTRODUCTION:Metastases to the central nervous system are the most common cause of malignant intracranial tumors in adults. Current standard of care includes surgery and radiation, but overall survival remains poor. A range of systemic therapies are emerging as promising treatment options for these patients. AREAS COV...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1080/13543784.2020.1836154
更新日期:2020-12-01 00:00:00
abstract:INTRODUCTION:Obesity is a major health threat in the Western world because of its high incidence and prevalence, and its association with metabolic and cardiovascular disease as well as cancer. The reduction of food intake in obese patients can be achieved only transiently (generally for no longer than 6 months), in th...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.630660
更新日期:2011-12-01 00:00:00
abstract::While oral formulations of agonists at the serotonin (5-HT) receptor subdivisions 5-HT(1B/1D)--the "triptan" class of drugs--dominate the market for migraine therapy and while still more triptans are under development, recent research efforts have also explored other pharmacological avenues, which are mostly based on ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.12.1813
更新日期:2002-12-01 00:00:00
abstract::The introduction of HIV-1 protease inhibitors in 1995 ushered in the era of highly active antiretroviral therapy. For the first time, inhibition of two key enzymes responsible for HIV replication, reverse transcriptase and protease, was possible. The combination of two nucleoside reverse transcriptase inhibitors with ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.11.9.1295
更新日期:2002-09-01 00:00:00
abstract::The outcome of patients with gastrointestinal stromal tumors has been dramatically improved by therapy with imatinib mesilate (imatinib mesylate), a KIT and platelet-derived growth factor (PDGFR) tyrosine kinase inhibitor. Unfortunately, the majority of patients eventually experience disease progression due to drug re...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.16.10.1549
更新日期:2007-10-01 00:00:00
abstract:BACKGROUND:Pompholyx is a chronic relapsing inflammatory vesicobullous skin disease of the hands and feet belonging to the spectrum of eczema. Established treatments, both topical and systemic, are limited in efficacy, risk:benefit ratio and prevention of further relapses. New treatment options are needed. OBJECTIVE:T...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.17.6.897
更新日期:2008-06-01 00:00:00
abstract:INTRODUCTION:The small tyrosine kinase inhibitor Imatinib Mesylate (Gleevec) protects against diabetes, but it is not known how. AREAS COVERED:It has been suggested that islet amyloid and fibrotic deposits promote beta-cell failure and death, leading to Type-2 diabetes. As Imatinib is known to possess anti-fibrotic/am...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2012.724398
更新日期:2012-11-01 00:00:00
abstract::Overactive bladder (OAB) is a chronic distressing condition characterised by urinary urgency with or without urge incontinence, usually with frequency (voiding at least eight times daily) and nocturia. It affects millions of people worldwide independent of age, sex and race. The prevalence increases with age and is re...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.15.9.1017
更新日期:2006-09-01 00:00:00
abstract:INTRODUCTION:About 185,000,000 people worldwide are chronically infected with hepatitis C virus (HCV). Currently, the most successful HCV infection antiviral therapies reduce the chance of progression towards the advanced phases of the hepatopathy (liver cirrhosis, hepatocellular carcinoma and death). Recently, however...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1059820
更新日期:2015-01-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:The sodium/hydrogen exchanger-1 (NHE-1/SLC9A1) is a ubiquitous plasma membrane protein whose main role is maintenance of intracellular pH and volume. NHE-1 plays a role in atherogenesis; however, its clinical relevance has not yet been established. AREAS COVERED IN THIS REVIEW:We herein review ...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2010.532123
更新日期:2010-12-01 00:00:00
abstract::Myocardial protection through pharmacological approaches represents a large therapeutic challenge and is an important therapeutic strategy in patients with coronary artery disease, particularly after myocardial infarction. Extensive animal experiments have repeatedly demonstrated the efficacy of sodium-hydrogen exchan...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.9.5.1099
更新日期:2000-05-01 00:00:00
abstract::The vasopressin system is complex and interacts with the central nervous, cardiovascular, renal, and hematological systems. Vasopressin plays an important role in the control of blood osmolarity and vascular tone, but is also involved in many other physiological events, which are mediated mainly via three types of vas...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903066764
更新日期:2009-08-01 00:00:00
abstract::Human cytomegalovirus (HCMV) is the most common viral opportunistic infection in patients suffering with acquired immunodeficiency virus (AIDS). HCMV is a systemic infection that may infect several sites in the body, including the retina, gastrointestinal tract, lungs, liver, and central nervous system. Retinitis is t...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.9.1157
更新日期:1997-09-01 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::Ovarian stimulation during infertility treatment is used either alone or in conjunction with intrauterine insemination and assisted reproductive technologies. At the present time, the two main medications used for ovarian stimulation include an oral antioestrogen, clomiphene citrate and injectable gonadotrophins. In s...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.12.3.353
更新日期:2003-03-01 00:00:00
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
doi:10.1517/13543784.14.7.913
更新日期:2005-07-01 00:00:00
abstract::Presentations at the William Harvey Research Conference on PDE Inhibitors described the molecular biology, biochemical regulation. pharmacology, and therapeutic utility of inhibitors of cyclic nucleotide phosphodiesterases (PDEs). Most of the talks focused on PDE4 and PDE5. two members of the 11-member PDE family that...
journal_title:Expert opinion on investigational drugs
pub_type:
doi:10.1517/13543784.9.3.621
更新日期:2000-03-01 00:00:00
abstract::Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) each occur in about 0.5-1.5% of the population in westernised countries, and primarily affect women. At present, a variety of pharmacological treatments are used in addition to psychotherapy, with antidepressants being most the common. Current...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.4.427
更新日期:1997-04-01 00:00:00
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
doi:10.1517/13543784.7.12.1977
更新日期:1998-12-01 00:00:00
abstract:INTRODUCTION:Since the discovery of the activating V617F mutation in Janus kinase 2 (JAK2), a number of pharmacologic inhibitors of JAK2 have entered clinical trials for patients with myelofibrosis. However, ruxolitinib, approved in 2011, remains the only one currently available for treatment of myelofibrosis, with man...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1080/13543784.2017.1323871
更新日期:2017-06-01 00:00:00
abstract:INTRODUCTION:There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infect...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2015.1005205
更新日期:2015-03-01 00:00:00
abstract::Since the introduction of the first through the skin (TTS) therapeutic in 1980, a total of 34 TTS products have been marketed and numerous drugs have been tested by more than 50 commercial organisations for their suitability for TTS delivery. Most of the agents which have been tested have had low molecular weights, du...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章
doi:10.1517/13543784.6.12.1887
更新日期:1997-12-01 00:00:00
abstract:INTRODUCTION:The progression of the mammalian cell cycle is driven by the transient activation of complexes consisting of cyclins and cyclin-dependent kinases (CDKs). Loss of control over the cell cycle results in accelerated cell division and malignant transformation and can be caused by the upregulation of cyclins, t...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543784.2011.628985
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND:Today, propofol or 2,6-diisopropylphenol is the anesthetic mainly used for monitored anesthetic care sedation and during intravenous anesthesia. The formulation, a lipid macroemulsion, shows several disadvantages. Therefore, during the past years considerable scientific effort has been undertaken to find eit...
journal_title:Expert opinion on investigational drugs
pub_type: 杂志文章,评审
doi:10.1517/13543780903193063
更新日期:2009-10-01 00:00:00