Abstract:
BACKGROUND:Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies including breast, prostate, and lung cancer are being tested. Although many CK2 inhibitors exist, only a few have emerged as selective inhibitors that are potent and effective. CX-4945 is a selective, orallybioavailable small molecule inhibitor, which has shown encouraging results in pre-clinical models of leukemia. METHODS:In this review we will elaborate on the structure and physiological function of the CK2 protein as well as its role in cancer. We will review, in depth, the role of CK2 in leukemia and its mechanisms of tumorigenesis via phosphorylation of the tumor suppressor protein Ikaros. We will discuss both the importance of Ikaros in leukemia suppression and the restoration of Ikaros' tumor suppressor function after CK2 inhibition by CX-4945 (a CK2-specific inhibitor). RESULTS:CK2 is an oncogene that is overexpressed in hematological malignancies. In high risk Pre-B ALL, CK2 phosphorylates Ikaros tumor suppressor and promotes leukemogenesis. Inhibition of CK2 using CX4945 restores Ikaros function and leads to anti leukemic effects in vitro and in pre-clinical leukemia models. CONCLUSION:CK2 is an attractive target in treatment of various cancers. Currently only a few specific CK2 inhibitors are available. Preclinical studies using CK2 inhibitor, CX4945 in high risk pediatric leukemias have shown promising results and warrants further testing in other types of leukemia.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Gowda C,Sachdev M,Muthusami S,Kapadia M,Petrovic-Dovat L,Hartman M,Ding Y,Song C,Payne JL,Tan BH,Dovat Sdoi
10.2174/1381612822666161006154311subject
Has Abstractpub_date
2017-01-01 00:00:00pages
95-107issue
1eissn
1381-6128issn
1873-4286pii
CPD-EPUB-78804journal_volume
23pub_type
杂志文章,评审abstract::Alzheimer disease (AD) is characterized by excessive deposition of amyloid beta-peptides (Abeta peptides) in the form of senile plaques as well as neurofibrillary tangles (NFTs) in the brain. In the amyloidogenic pathway, the amyloid-beta precursor protein (APP) is cleaved by beta-secretase first, followed by gamma-se...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161206778792994
更新日期:2006-01-01 00:00:00
abstract::Providing novel treatments to help cancer patients live longer and have better lives remains one of the biggest challenges of the pharmaceutical industry. Today much is known about the molecular and genetic causes of cancers thus facilitating the development of novel targeted cancer drugs with improved risk-benefit ra...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784246234
更新日期:2008-01-01 00:00:00
abstract::Drug-drug interactions may occur when to combine two or more drugs and may cause some adverse events such as Cardiotoxicity, Central neurotoxicity, Hepatotoxicity, etc. Although a large number of researchers who are proficient in pharmacokinetics and pharmacodynamics have been engaged in drug assays and trying to find...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612827666210127122312
更新日期:2021-01-27 00:00:00
abstract::Mitochondria are involved in different physiological and pathological processes that are crucial for tumor cell physiology, growth and survival. Since cancer cells have frequently disrupted different cell death pathways that promote their survival, mitochondria may be key organelles to promote cell death in cancer cel...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211796904803
更新日期:2011-01-01 00:00:00
abstract::DNA methyltransferase (DNMT) and histone deacetylase are key enzymes mediating the epigenetic regulation of gene expression. DNA hypermethylation and/or histone deacetylation in promoter regions is often associated with downregulation or silencing of transcription. Epigenetic silencing of tumor suppressor genes plays ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990527
更新日期:2014-01-01 00:00:00
abstract::G protein receptor kinase 2 (GRK2) has been for years mainly considered the negative regulator of the cardiac β adrenergic signaling. However GRK2 is a ubiquitous molecule and its kinase activity and scaffold properties brought to several investigations which have evidenced its involvement in pathophysiology of extra-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212799040493
更新日期:2012-01-01 00:00:00
abstract::The intracellular hydric balance is an essential process of mammalian cells. The water movement across cell membranes is driven by osmotic and hydrostatic forces and the speed of this process is dependent on the presence of specific aquaporin water channels. Since the molecular identification of the first water channe...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781368738
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Nuts have been an indispensable component of the human diet for hundreds because of their unique nutrient composition and are thought to play a beneficial part in the prevention of cardiovascular diseases. OBJECTIVE:To evaluate the extent, validity and presence of evidence for studies investigating the impa...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析,评审
doi:10.2174/1381612822666161010121356
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Vaginal infections caused by non-albicans species have become common in women of all age groups. The resistance of species such as Candida parapsilosis to the various antifungal agents is a risk factor attributed to these types of infections, which instigates the search for new sources of active compounds in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200317131041
更新日期:2020-01-01 00:00:00
abstract::Neuroinflammation is a common characteristic of several mental health conditions such as major depression, bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia (SCHZ). Inflammatory processes trigger and/or further deteriorate mental functions and are regarded as targets for therapeutic drug develo...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282210160304112511
更新日期:2016-01-01 00:00:00
abstract::The mechanisms and factors causing or influencing degenerative diseases require tailor-made solutions. Natural polysaccharides are among the most versatile building units of the novel drug delivery systems. Their properties can be easily tailored to specific needs because they depend not only on the first-order struct...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212800492831
更新日期:2012-01-01 00:00:00
abstract::Regeneration of bone requires the coordinated processes of angiogenesis and osteogenesis. These repair mechanisms are closely linked through both direct cell-cell contact and indirect paracrine signaling among osteoblasts, endothelial cells, and other cell types. The vasculature provides a source of nutrients, oxygen,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319190007
更新日期:2013-01-01 00:00:00
abstract::Research on Substance P (SP) has, until recently, focused on its role in pain and inflammation. However, a report that NK(1) receptor antagonists have utility in the treatment of depression has stimulated research into the function of SP and the NK(1)receptor in anxiety and depression. The distribution of SP and the N...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053764779
更新日期:2005-01-01 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::Reducing sugars can react non-enzymatically with amino groups of proteins and lipids to form irreversibly cross-linked macroprotein derivatives called as advanced glycation end products (AGEs). Cross-linking modification of extracellular matrix proteins by AGEs deteriorate their tertiary structural integrity and funct...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666161021155502
更新日期:2017-01-01 00:00:00
abstract::BMS-378806 is a prototype of a new class of small molecule HIV-1 inhibitors that blocks viral attachment to cells. This compound exhibits potent inhibitory activity against a panel of HIV-1 laboratory and clinical isolates (M- and T-tropic), selective for HIV-1 and inactive against HIV-2, SIV and a panel of other viru...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384565
更新日期:2004-01-01 00:00:00
abstract::The pivotal therapeutic role of myocardial metabolic modulation in ischemic heart disease (IHD) is increasingly recognized. Among the others, inhibitors of free fatty acids (FFA) oxidation have been consistently shown to play an important role in the therapeutic strategy of IHD patients. Additionally, abnormalities of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787582093
更新日期:2009-01-01 00:00:00
abstract::The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes o...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190717104547
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Cancer is the world's second-largest cause of death, with an estimated 9.6 million fatalities in 2018. Malignant tumour (cancer) is caused by a mixture of genetic modifications due to the environmental variables that tend to activate or inactivate different genes, ultimately resulting in neoplastic transform...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200701151403
更新日期:2020-01-01 00:00:00
abstract::Virtual screening, especially the structure-based virtual screening, has emerged as a reliable, cost-effective and time-saving technique for the discovery of lead compounds. Here, the basic ideas and computational tools for virtual screening have been briefly introduced, and emphasis is placed on aspects of recent dev...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043452721
更新日期:2004-01-01 00:00:00
abstract::The increasing prevalence of persistent biofilm infections, such as wound infections, chronic lung infections or medical device- related infections, which usually tolerate conventional antibiotic treatment, calls for the development of new therapeutic strategies. To date, antimicrobial peptides (AMPs) are considered a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140905124312
更新日期:2015-01-01 00:00:00
abstract::Parkinson's disease (PD) is a movement disorder caused by degeneration of the nigrostriatal dopamine (DA) neurons in the substantia nigra pars compacta and the resultant deficiency in the neurotransmitter DA at the nerve terminals in the striatum. We and other investigators found increased levels of pro-inflammatory c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053381620
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Inflammatory bowel disease (IBD) is a group of intestinal disorders characterised by chronic relapsing inflammation of the small intestine and colon. IBD manifests as either ulcerative colitis or Crohn's disease and increases the risk of developing colorectal cancer. METHODS:Here, we have reviewed current t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170201162414
更新日期:2017-01-01 00:00:00
abstract::The serotonergic system is involved in pathomechanisms of both epilepsy and neuropathic pain. So far, participation in the epileptogenesis and maintenance of epilepsy was proved for 5-HT1A, 5-HT2C, 5-HT3, 5-HT4 and 5-HT7 receptors as well as 5-HTT serotonin transporter. Depending on the receptor type or its localizati...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666141121114917
更新日期:2015-01-01 00:00:00
abstract::Hypertension and insomnia are very common and often coexist. There is evidence to suggest that the increasing prevalence of arterial hypertension in the past decade might be related both to an increased prevalence of insomnia and to the decline of sleep duration due to modern lifestyle. The aim of this paper is to rec...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319130009
更新日期:2013-01-01 00:00:00
abstract::After years of pre-clinical and clinical testing monoclonal antibodies (mAbs) finally offer new therapeutic choices for patients with haematological and solid malignancies both as unconjugated antibody and as vectors to target radionuclides in radioimmunotherapy (RIT). In recent years some of the most exciting clinica...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003399257
更新日期:2000-09-01 00:00:00
abstract::Histone lysine methylation can be modified by various writers and erasers. Different from other epigenetic modifications, mono-, di, and tri- methylation distinctly modulate chromatin structure and thereby contribute to the regulation of DNA-based nuclear processes such as transcription, replication and repair on thei...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160715125417
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Spice and spice-derived compounds have been identified and explored for their health benefits since centuries. One of the spice long pepper has been traditionally used to treat chronic bronchitis, asthma, constipation, gonorrhea, paralysis of the tongue, diarrhea, cholera, malaria, viral hepatitis, respirato...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160601103027
更新日期:2016-01-01 00:00:00
abstract::The clinical presentation of heart disease is different between men and women and this distinction is pivotal for a correct diagnosis and an adequate treatment. However, the definition of symptoms classically associated with heart disease is mainly based on the characteristics of those reported in men. Chest pain or c...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161211795656927
更新日期:2011-01-01 00:00:00
abstract::Aberrant expression of chemokines and their receptors play causative roles in the pathophysiology of numerous autoimmune and inflammatory disease processes. Moreover, an integral step in HIV infection involves binding to chemokine receptors, and hence chemokines are intimately linked to HIV-related diseases. Therefore...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023393233
更新日期:2002-01-01 00:00:00