Abstract:
BACKGROUND:Intestinal β-glucuronidase enzyme has a significant importance in colorectal carcinogenesis. Specific inhibition of the enzyme helps prevent immune reactivation of the glucuronide- carcinogens, thus protecting the intestine from ROS (Reactive Oxidative Species) mediatedcarcinogenesis. OBJECTIVES:Advancement in In-silico based techniques has provided a broad range of studies to carry out the drug design and development process smoothly using SwissADME and BOILED-Egg tools. METHODS:In our designed case study, we used SwissADME and BOILED-Egg predictive computational tools to estimate the physicochemical, human pharmacokinetics, drug-likeness, medicinal chemistry properties and membrane permeability characteristics of our recently In-vitro evaluated novel β-Glucuronidase inhibitors. RESULTS:Out of the eleven screened potent inhibitors, compound (8) exhibited excellent bioavailability radar against the six molecular descriptors, good (ADME) Absorption, Distribution, Metabolism and Excretion along with P-glycoprotein, CYP450 isozymes and membranes permeability profile. On the basis of these factual observations, it is to be predicted that compound (8) can achieve in-vivo experimental clearance efficiently, Therefore, in the future, it can be a drug in the market to treat various disorders associated with the overexpression of β-Glucuronidase enzyme such as various types of cancer, particularly hormone-dependent cancer such as (breast, prostate, and colon cancer). Moreover, other compounds (1-7, & 9-11), have also shown good predictive pharmacokinetics, medicinal chemistry, BBB and HIA membranes permeability profiles with slight lead optimization to obtain improved results. CONCLUSION:In consequence, in-silico based studies are considered to provide robustness for a rational drug design and development approach to avoid the possibility of failures of drug candidates in the later stages of drug development phases. The results of this study effectively reveal the possible attributes of potent β-Glucuronidase inhibitors, for further experimental evaluation.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Yousuf Mdoi
10.2174/1568009619666190320102238subject
Has Abstractpub_date
2019-01-01 00:00:00pages
906-918issue
11eissn
1568-0096issn
1873-5576pii
CCDT-EPUB-97443journal_volume
19pub_type
杂志文章abstract::Breast cancer is one of the most common malignancies among women, representing nearly 30% of newly diagnosed cancers every year. Till date, various therapeutic interventions, including surgery, chemotherapy, hormonal therapy, and radiotherapy are available and are known to cause a significant decline in the overall mo...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009615666141229152256
更新日期:2015-01-01 00:00:00
abstract::Angiogenesis is crucial for tumor development and progression, and antiangiogenetic therapy represents a promising approach for cancer treatment. Thus, the in-depth understanding of the molecular mechanism(s) regulating angiogenesis, together with the characterization of molecules expressed by endothelial cells and in...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009033481741
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular e...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200924154149
更新日期:2020-01-01 00:00:00
abstract::It has been estimated that greater than 35% of all human genes undergo alternative splicing. The process of alternative splicing is highly regulated and disruption of a splicing pattern can produce splice variants that have different functions. Certain splice variants that are associated with induction of cell death, ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009013334124
更新日期:2001-11-01 00:00:00
abstract::Heat shock protein 32 (Hsp32), also known as heme oxygenase-1 (HO-1), is a stress-related anti-apoptotic molecule, that has been implicated in enhanced survival of neoplastic cells and in drug-resistance. We here show that Hsp32 is expressed in most solid tumors and hematopoietic neoplasms and may be employed as a new...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800909789057024
更新日期:2009-08-01 00:00:00
abstract::The integrin family of cell surface receptors integrates cell-extracellular matrix interactions with the cell cytoskeleton and signalling across the cell membrane, resulting in an important role in cell adhesion, mobility and migration, proliferation, and survival. Changes in the number and identity of integrin recept...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909788486713
更新日期:2009-06-01 00:00:00
abstract::Breast cancer is one of the most prevalent and devastating malignant diseases in women worldwide. Fortunately, while breast cancer incidence is still increasing, its death rate is declining. This is mainly due to early diagnosis and potent therapies such as blockade of estrogen receptor- or of ErbB2 (HER2-neu) membran...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009611313020008
更新日期:2013-02-01 00:00:00
abstract::Nuclear Hormone Receptors (NR) represent one of the most promising protein families in terms of therapeutic applications. These transcription factors are naturally switched on and off by small molecule hormones presenting physico-chemical properties very similar to therapeutic chemical entities. NRs represent therefor...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023333845
更新日期:2002-09-01 00:00:00
abstract::Autophagy is an intracellular lysosomal/vacuolar degradation system, in which the inner cytoplasmic cell membrane is degraded by the lysosomal hydrolases, followed by the resulting products released back into the cytosol. It is involved in many physiological processes which are crucial for cell growth and survival. Ho...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170330124819
更新日期:2018-01-01 00:00:00
abstract::Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia-positive chromosome deriving from a translocation between chromosomes 22 and 9. The oncogenic product of this aberrant chromosome is the constitutively active tyrosine kinase BCR-ABL that is responsible for leukemic cell growth,...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800912800673239
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Epidermal growth factor receptor (EGFR) is a well-recognised drug target exploited for treating non-small cell lung cancer (NSCLC). Gefitinib and erlotinib are first generation clinically employed inhibitors used against EGFR activating mutants. However, during course of treatment these inhibitors become ine...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170330112842
更新日期:2017-01-01 00:00:00
abstract::The capacity to induce new blood vessel formation or to repair damaged vessels is an attractive idea that has, for a long time, captured the attention and imagination of researchers. Beside the identification of the pro-angiogenic growth factors and their counterpart inhibitors, the discovery of endothelial progenitor...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910793358041
更新日期:2010-12-01 00:00:00
abstract::Sporadic colorectal cancer develops through a number of functional mutations. Key events are mutually exclusive mutations in BRAF or RAS oncogenes. Signatures for BRAF oncogene have been revealed in melanoma. In a previous study we have reported a molecular signature for HRAS and KRAS mutations in colorectal cell line...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800912802429364
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:The solute carrier family 7 (SLC7) can be categorically divided into two subfamilies, the L-type amino acid transporters (LATs) including SLC7A5-13, and SLC7A15, and the cationic amino acid transporters (CATs) including SLC7A1-4 and SLC7A14. Members of the CAT family transport predominantly cationic amino ac...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009619666190802135714
更新日期:2019-01-01 00:00:00
abstract::Targets for cancer therapy are conventionally selected by identification of molecules acting downstream of established tumour suppressors and oncoproteins, such as p53, c-Myc and Ras. However, the forward genetics approach provides an alternative, conceptually distinct, strategy for identifying target molecules de nov...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract::Degradation of extracellular matrix is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009053765799
更新日期:2005-05-01 00:00:00
abstract::Obesity is rapidly becoming a global phenomenon. This is more than a cosmetic issue as obesity is associated with several life-threatening diseases, including colon cancer. Insulin resistance and inflammation, underlying factors in obesity-related diseases, promote colonocyte proliferation and suppress programmed cell...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908786241087
更新日期:2008-11-01 00:00:00
abstract::Drug delivery systems are under intense investigation all around the world, especially in oncology research. Indeed, in some cases, like bone metastasis, nanodrugs may represent the last and best choice for both treatment and imaging of early cancer foci. Nuclear medicine has been using MDP labelled with 99mTc as radi...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009615666150407125020
更新日期:2015-01-01 00:00:00
abstract::Various signal transduction pathways have been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL), which is characterized by the progressive accumulation of monoclonal CD5+ B cells in the blood. B cell receptor (BCR) signaling appears to have a crucial role in disease onset and is thought to be induc...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160408145623
更新日期:2016-01-01 00:00:00
abstract::Heat shock proteins (HSPs) are molecular chaperones that stabilize folding and conformation of normal as well as oncogenic proteins. These chaperones thereby prevent the formation of protein aggregates. HSPs are often overexpressed in human malignancies, including AML. HSP90 is the main chaperon required for the stabi...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909789271486
更新日期:2009-09-01 00:00:00
abstract::Recent publications on the molecular characterization of malignant glioma have had profound impact on the appreciation of tumoral heterogeneity within and between patients. Both these phenomena are implicated in the variability in clinical outcome between patients, as well as the inevitable recurrence of these tumors ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160813191809
更新日期:2017-01-01 00:00:00
abstract::Several subtypes of T cells are located in a tumor environment, each of which supplies their energy using different metabolic mechanisms. Since the cancer cells require high levels of glucose, the conditions of food poverty in the tumor environment can cause inactivation of immune cells, especially the T-effector cell...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200720010647
更新日期:2020-01-01 00:00:00
abstract::The application of nanotechnology to biomedical research is expected to have a major impact leading to the development of new types of diagnostic and therapeutic tools. One focus in nanobiotechnology is to develop safe and efficient drug/gene delivery vehicles. Research into the rational delivery and targeting of phar...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911794328411
更新日期:2011-02-01 00:00:00
abstract::The actin microfilament network is important in maintaining cell shape and function in eukaryotic cells. It has a multitude of roles in cellular processes such as cell adhesion, motility, cellular signalling, intracellular trafficking and cytokinesis. Alterations in the organisation of the cytoskeleton and changes in ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800906776842948
更新日期:2006-05-01 00:00:00
abstract::Over the past two decades, a number of chemical entities have been investigated in the continuing quest to reverse P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in cancer cells and some have undergone clinical trials, but currently none are in clinical use. Unfortunately, most of these agents suffer clinic...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909788166619
更新日期:2009-05-01 00:00:00
abstract::Tumor heterogeneity within various cancer types including breast carcinoma is pivotal in the manifestations of tumor hallmarks. Tumor heterogeneity is seen as a common landscape where intra-tumoral components including cellular and non-cellular factors create an interface with outside environment that leads to the uni...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009618666180628102247
更新日期:2019-01-01 00:00:00
abstract::Selection of treatment options for clinically localized prostate cancer is based on a host of factors including the patient's age, overall health status, potential complications, clinical tumor stage and Gleason score. It is widely acknowledged that androgen independent disease remains the main obstacle to improving t...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043481623
更新日期:2004-02-01 00:00:00
abstract::Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009618666181010091246
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Approximately one third of Diffuse Large B cell Lymphomas (DLBCL) are refractory or relapse. Novel therapeutic approaches under scrutiny include inhibitors of B-cell receptor (BCR) signaling. Protein kinase CK2 propels survival, proliferation and stress response in solid and hematologic malignancies and prom...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009617666170427110450
更新日期:2018-01-01 00:00:00
abstract::Bid, a BH3-only Bcl-2 family member, is proven to be a pivotal molecule for the regulation of tumorigenesis by its multiple functions in promoting apoptosis, survival and proliferation. Growing evidence supports that Bid has double roles with respect to stress-response. In most cases it functions in a truncated form, ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791859515
更新日期:2010-09-01 00:00:00