Abstract:
:Cancer therapies through ionizing radiation or chemotherapeutic treatment may result in DNA double strand breaks (DSBs) in cell. DNA-PK has emerged as an attractive target for drug discovery efforts toward DSBs repair and in V(D)J recombination. Hence, the search for potent and selective DNA-PK inhibitors has received particular attention and several series of activity inhibitors have been reported. In this article, we gave a report of the DNA-PK activation and the corresponding inhibitors, which belong to different chemical classes. Then homology modeling and molecular dynamics (MD) simulation were used to build the 3D model of DNA-PK receptor based on the X-ray structure of PI3K. All of the ligands were docked into the putative binding site of the 3D model of DNA-PK using the flexible docking method, and the probable interaction model between DNA-PK and the ligands were obtained. Based on the docking conformations and their alignment inside the binding pocket of DNA-PK, 3D QSAR analyses were performed on 259 ligands using CoMFA and CoMSIA methods. Both CoMFA and CoMSIA provide statistically valid models with good correlation and predictive power (CoMFA: q2 = 0.563, r(2) =0.876; CoMSIA: q(2) = 0.503, r(2) =0.870). Our models would offer help to better comprehend the structure-activity relationship existent for this class of compounds and also facilitate the design of new inhibitors with good chemical derivsity.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Cao R,Zeng H,Zhang Hdoi
10.2174/138161209789649484subject
Has Abstractpub_date
2009-01-01 00:00:00pages
3796-825issue
32eissn
1381-6128issn
1873-4286journal_volume
15pub_type
杂志文章abstract::Pancreatic cancer is one of the most fatal human malignancies. Though a relatively rare malignancy, it remains one of the deadliest tumors, with an extremely high mortality rate. The prognosis of patients with pancreatic cancer remains poor; only patients with small tumors and complete resection have a chance of a com...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128112092395
更新日期:2012-01-01 00:00:00
abstract::Gene delivery, a process of introducing foreign functional nucleic acids into target cells, has proven to be a very promising tool for inducing specific gene expression in host cells. Many different technologies have been developed for efficient gene delivery. Among them, electroporation has been adopted in gene deliv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666151027152121
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Medical treatments are used either alone or in combination with assisted reproductive techniques for treatment of infertile patients with hypergonadotropic hypogonadism. A wide range of treatment options such as gonadotropins, aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs) and the...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666201102110456
更新日期:2020-11-01 00:00:00
abstract::The vasoconstrictive and antidiuretic physiologic properties of vasopressin (antidiuretic hormone) have long been known. Until recently however, vasopressin was mostly used for diabetes insipidus and noctournal enuresis. This review summarizes the growing body of evidence regarding the perioperative use of vasopressin...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803832326
更新日期:2012-01-01 00:00:00
abstract::Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later s...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612053507477
更新日期:2005-01-01 00:00:00
abstract::A wide range of peptides and polypeptides can be appended to either the N- or C-terminus of G protein-coupled receptors without disrupting substantially ligand binding and signal transduction. Following fusion of fluorescent proteins, reporter gene constructs or G protein alpha subunits to the C-terminal tail of a rec...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384295
更新日期:2004-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is marked by cognitive dysfunctions and existence of neuropathological hallmarks such as amyloid plaques, and neurofibrillary tangles. It has been observed that a persistent immune response in the brain has appeared as another neuropathological hall...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200531151004
更新日期:2020-05-31 00:00:00
abstract::Protein stability of hypoxia-inducible factor (HIF)alpha subunits is regulated by the oxygen-sensing prolyl-4-hydroxylase domain (PHD) enzymes. Under oxygen-limited conditions, HIFalpha subunits are stabilized and form active HIF transcription factors that induce a large number of genes involved in adaptation to hypox...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789649411
更新日期:2009-01-01 00:00:00
abstract::Superparamagnetic iron oxide nanoparticles (SPIONs) comprise a fundamental technology class within the emerging field of nanomedicine, and have been extensively researched for cancer imaging and therapy. This review article will discuss the chemistry and design considerations associated with the synthesis of SPIONs an...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:
更新日期:2013-01-01 00:00:00
abstract::Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6-mercaptopurine (6-MP) are not effective in one-third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790112773
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:In Alzheimer's disease (AD), modification of astrocytic properties is a well-known and documented fact, but their involvement in pathophysiology has only been examined in recent years. One distinct hallmark of AD is reactive gliosis which are represented in microglial and astrocytic phenotype changes. This r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666171004151215
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Cell-cell adhesion is essential in maintaining the structure and function of an organ. Several adhesion molecules have recently been identified as associated with heroin dependence in both genetic and peripheral plasma studies. METHODS AND RESULTS:We reviewed literature concerning studies on adhesion molecu...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200116144147
更新日期:2020-01-01 00:00:00
abstract::α-Synuclein aggregation is centrally implicated in Parkinson's disease (PD). It involves multi-step nucleated polymerization process via the formation of dimers, soluble toxic oligomers and insoluble fibrils. In the present study, we synthesized a novel compound viz., Curcumin-glucoside (Curc-gluc), a modified form of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/138161212798919093
更新日期:2012-01-01 00:00:00
abstract::Drug designing targeting protein-protein interactions is challenging. Because structural elucidation and computational analysis have revealed the importance of hot spot residues in stabilizing these interactions, there have been on-going efforts to develop drugs which bind the hot spots and out-compete the native prot...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990073
更新日期:2014-01-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is one of the main endogenous pro-angiogenic cytokines. Inhibition of the VEGF signaling pathways is an effective treatment for cancer patients. In addition, local anti- VEGF therapy was developed and established to treat proliferative diabetic retinopathy, age-related macular...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150225120314
更新日期:2015-01-01 00:00:00
abstract::In recent years, nanosuspensions have been accepted as a valuable drug delivery system for poorly water-soluble drugs. Topdown and bottom-up technologies are the two main approaches for generating nanosuspensions. Several products manufactured by the top-down technologies have been successfully commercialized demonstr...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990401
更新日期:2014-01-01 00:00:00
abstract::Pancreatic cancer is hallmarked by aggressive biology and extreme lethality and very high mortality rates. The underlying molecular mechanism of its rapid development and progression is unclear, however. Recent identification and functional validation of nitric oxide (NO) production in pancreatic cancer suggest a role...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210790232194
更新日期:2010-01-01 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 tumor cell growth inhibitory activities (log 1/GI(50)) of 166 anticancer agents studied at the National Cancer Institute (NCI) in vitro anticancer screening program have allowed us to analyze the relative importance of physicochemical parameters in influencing the inhibitory activities. Increased molecular weight,...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612043384925
更新日期:2004-01-01 00:00:00
abstract::Unhealthy diet and alcohol are serious health problems, especially in adolescents and young adults. "Binge" is defined as the excessive and uncontrolled consumption of food (binge eating) and alcohol (binge drinking). Both behaviors are frequent among young people and have a highly negative impact on health and qualit...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200316153317
更新日期:2020-01-01 00:00:00
abstract::Opioid peptides showing selectivity for delta receptor have been isolated from enzymatic digests of plant proteins. Five peptides were derived from wheat gluten, and named gluten exorphins A5, A4, B5, B4 and C. Two opioid peptides were also released from spinach ribulose-bisphosphate-carboxylase/oxygenase (Rubisco), a...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612033454838
更新日期:2003-01-01 00:00:00
abstract::Growth factors (GFs) are extracellular signaling polypeptides regulating cell proliferation, differentiation and survival. They exert a wide spectrum of biological activities selectively binding to and activating specific membrane receptors which then transfer the message to cell interior inducing specific biochemical...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788682235
更新日期:2009-01-01 00:00:00
abstract::In recent years, Aβ aggregation prevention, one of the most concerned strategies in drug development has been carefully assessed to treat Alzheimer's disease. Aβ peptides can transform structurally from random coil monomer into β-stranded protofibril via multiple oligomeric states. Among the various Aβ species, the id...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612824666180813093420
更新日期:2018-01-01 00:00:00
abstract::Oxidative stress is often considered as a causative factor in carcinogenesis. In addition, current knowledge recognizes oxidative stress as a mechanism by which various cancer therapies act against cancer. To ameliorate the side effects of cancer therapy, many of the patients suffering from cancer are subject to adjuv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612820666140826152822
更新日期:2014-01-01 00:00:00
abstract::Recent advances in the fabrication, characterization and application of micro- and nano-particles that possess a non-uniform internal structure are reviewed. The particle structures include core-shell particles, particles with multiple cores or a multi-layered structure, porous particles with both regular and random p...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612811319350007
更新日期:2013-01-01 00:00:00
abstract::The phenomenon of blood serum atherogenicity was described as the ability of human serum to induce lipid accumulation in cultured cells. The results of recent two-year prospective study in asymptomatic men provided the evidence for association between the changes in serum atherogenicity and dynamics of carotid intima-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612820666140212194614
更新日期:2014-01-01 00:00:00
abstract::LIM (Lin-11, Isl-1, Mec-3), RING (Really interesting new gene), PHD (Plant homology domain) and MYND (myeloid, Nervy, DEAF-1) domains are all zinc-binding domains that ligate two zinc ions. Unlike the better known classical zinc fingers, these domains do not bind DNA, but instead mediate interactions with other protei...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789271861
更新日期:2009-01-01 00:00:00
abstract::Opiates lack potent analgesic efficacy in neuropathic pain although it is now generally accepted that the poor effect of these drugs reflects a reduction in their potency. Reduction of morphine antinociceptive potency was postulated to be due to the fact that nerve injury altered the activity of opioid systems or opio...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612054865055
更新日期:2005-01-01 00:00:00
abstract::Nesfatin-1, derived from the precursor NEFA/nucleobindin2 (NUCB2), was initially identified as a feeding-suppressing neuropeptide, acting at central (mainly, hypothalamic) levels in a leptin-independent manner. However, recent experimental evidence strongly suggests that, rather than being a simple anorectic hypothala...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161281939131127142531
更新日期:2013-01-01 00:00:00
abstract::ADAM (a disintegrin and metalloproteinase) proteins have a predominant role in the protein ectodomain shedding of membrane-bound molecules. ADAMs have emerged as critical regulators of cell-cell signaling during development and homeostasis, and are believed to contribute to pathologies, such as cancer, where their reg...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209788682415
更新日期:2009-01-01 00:00:00