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Current Drug Metabolism

Ke Chen, Jinwei Zhong, Lin Hu, Ruliu Li, Qun Duc, Jiazhong Cai, Yanwu Li, Yong Gao, Xiaona Cui, Xiaoying Yang, Xiaojie Wu, Lu Yao, Juji Dai, Yan Wang, Haiyong Jin
PXR (pregnane X receptor) and CAR (constitutive androstane receptor) are termed as xenobiotic receptors, which are known as core factors in the regulation of the transcription of metabolic enzymes and drug transporters. However, accumulating evidence has shown that PXR and CAR exert their effects on energy metabolism through the regulation of gluconeogenesis, lipogenesis, and β-oxidation. Therefore, PXR and CAR may become new therapeutic targets for metabolic syndrome, including obesity and diabetes. In this review, we will summarize recent advances to show how xenobiotic receptors regulate energy metabolism...
September 18, 2018: Current Drug Metabolism
Vivek K Chaturvedi, Anshuman Singh, Vinay K Singh, M P Singh
Background- Nanotechnology is gaining significant attention worldwide for cancer treatment. Nano-biotechnology encourages the combination of diagnostics with therapeutics, which is a vital component of a customized way to deal with the malignancy. Nanoparticles are being used as Nanomedicine which participates in diagnosis and treatment of various diseases including cancer. The unique characteristic of Nanomedicine i.e. their high surface to volume ratio enables them to tie, absorb, and convey small biomolecule like DNA, RNA, drugs, proteins, and other molecules to the targeted site and thus enhances the efficacy of therapeutic agents...
September 18, 2018: Current Drug Metabolism
Anil K Sharma, Var Ruchi Sharma, Girish K Gupta, Ghulam Md Ashraf, Mohammad A Kamal
BACKGROUND: Advanced glycation end products (AGEs) are basically the end result of glycation of proteins and/or lipids in the presence of sugars. Specific cases of hyperglycemia have been reported with increased propensity of generation of AGEs. Many chronic and deadly diseases such as diabetes, cancer and neurodegenerative disorders have been known to be caused as a result of generation of AGEs. The role of glutathione (GSH) metabolism and its intricate association with AGEs has also been well established in breast cancer prognosis and treatment...
September 11, 2018: Current Drug Metabolism
Nantao Zheng, Kairou Wang, Weihua Zhan, Lei Deng
Virus-host protein interactions play essential roles in viral infection and antiviral defenses. Targeting critical viral-host protein-protein interactions (PPIs) has enormous application prospects for therapeutics. Using experimental methods to evaluate all possible virus-host PPIs takes a great deal of money and time. Recent growth in computational identification of virus-host PPIs provides new opportunities for gaining biological insights, including applications in disease control. We provide an overview of recent computational approaches for studying virus-host PPI interactions...
August 29, 2018: Current Drug Metabolism
Li Di
Carboxylesterases (CES) play a critical role in catalyzing hydrolysis of esters, amides, carbamates and thioesters, and bioconverting prodrugs and soft drugs. Human CES1 is one of the most highly expressed drug metabolizing enzymes in the liver, while human intestine only expresses CES2. The unique tissue distribution of CES enzymes provides great opportunities to design prodrugs or soft drugs for tissue targeting. CES enzymes have moderate to high inter-individual variability and exhibit low to no expression in the fetus, but increase substantially during the first few months of life...
August 20, 2018: Current Drug Metabolism
Wen Zhang, Weiran Lin, Ding Zhang, Siman Wang, Jingwen Shi, Yanqing Niu
The identification of drug-target interactions is a crucial issue in drug discovery. In recent years, researchers have made great efforts on the drug-target interaction predictions, and developed databases, software and computational methods. In the paper, we review the recent advances of machine learning-based drug-target interaction prediction. First, we briefly introduce the datasets and data, and summarize features for drugs and targets which can be extracted from different data. Since drug-drug similarity and target-target similarity are important for many machine learning prediction models, we introduce how to calculate similarities based on data or features...
August 20, 2018: Current Drug Metabolism
Lin Ning, Bifang He, Peng Zhou, Ratmir Derda, Jian Huang
Peptide-Fc fusion drugs are a category of biological therapeutics in which the Fc region of an antibody is genetically fused to a peptide of interest. In this review, we summarize the key steps in peptide-Fc fusion technology and stress the main computational resources, tools, and methods that have been used in the rational design of peptide-Fc fusion drugs. Additionally, open questions about the computer-aided molecular design of peptide-Fc are raised. Answers to these questions by future research will certainly help make the transition from peptide leads to drugs on the market quicker and cheaper...
August 20, 2018: Current Drug Metabolism
Natalie Stephenson, Emily Shane, Jessica Chase, Jason Rowland, David Ries, Nicola Justice, Jie Zhang, Leong Chan, Renzhi Cao
Drug discovery, which is the process of discovering new candidate medications, is very important for pharmaceutical industries. At its current stage, discovering new drugs is still an expensive and time-consuming process, requiring Phases I, II and III for clinical trials. Recently, machine learning techniques in Artificial Intelligence (AI), especially the deep learning techniques which allow a computational model to generate multiple layers, have been widely applied and achieved state-of-the-art performance in various fields, such as speech recognition, image classification, bioinformatics, etc...
August 19, 2018: Current Drug Metabolism
Donna A Volpe
No abstract text is available yet for this article.
August 17, 2018: Current Drug Metabolism
Mohammad Alkhalil
Statins have been a major keystone in the management of patients with atherosclerotic cardiovascular disease. The benefits of inhibiting HMG CoA reductase, via statins, were translated into reduction in LDL-c (cholesterol) with proportionate decrease in cardiovascular events in response to the magnitude of LDL-c reduction. Despite major advances in pharmacological treatments, including the use of high-dose statins, there are urgent need to further reduce future cardiovascular risk. This is in particularly important since 1 out of 5 high-risk atherosclerotic patients who achieve low LDL-c return with a second cardiovascular event within five years...
August 16, 2018: Current Drug Metabolism
Wei Song, Meilin Liu, Junjun Wu, Hong Zhai, Yong Chen, Zhihong Peng
Triptolide, a bioactive component in Tripterygium wilfordii extracts, possess strong anti-proliferative activity on all 60-national cancer institute (NCI) cancer cell lines. The antitumor property of triptolide has made it become a promising anti-cancer drug. However, the widespread use of triptolide in the clinical practice is greatly limited for its multi-organ toxicity and narrow therapeutic window. All the toxic characteristics of triptolide are associated with the pharmacokinetics especially its distribution and accumulation in the target organ...
August 16, 2018: Current Drug Metabolism
Zhi Liu, Xin He, Lili Wang, Yunhua Zhang, Yue Hai, Rui Gao
This review summarizes the current research status of hepatotoxicity and points out that drug induced liver injury (DILI) remains an important scientific problem that urgently needs to be solved. Due to the special nature of Chinese Herbal medicine and the complexity of its clinical use, it is difficult to identify and evaluate its toxicity and resulting herb induced liver injury (HILI). At the same time, due to a lack of specific indicators, the direct and indirect long-term effects of Chinese Herbal Medicine on the liver are also difficult to be clinically determined...
August 13, 2018: Current Drug Metabolism
Eleonore Frohlich
No abstract text is available yet for this article.
August 6, 2018: Current Drug Metabolism
Stephen C Mitchell, Glyn B Steventon
Although it is believed widely that the various routes of xenobiotic metabolism are now all known and effectively understood, occasionally there emerges a metabolite that signals a novel biotransformation pathway, especially where the xenobiotic may in some way interact with the myriad processes of intermediary metabolism. There are a few reports in the literature where saturated short-chain dicarboxylic acids have been exploited as conjugating agents and these unusual xenobiotic metabolites subsequently excreted intact in the urine...
August 3, 2018: Current Drug Metabolism
Pengyuan Sun, Kexin Liu
BACKGROUND: Patients with hypertension usually have to be treated with angiotensin converting enzyme (ACE) inhibitors, and are therefore more exposed to drug-drug interactions (DDIs) by various mechanisms, especially the mechanisms based on drug metabolizing enzymes and transporters. OBJECTIVE: This review article focuses on the pharmacokinetic interaction mechanisms with ACE inhibitors based on drug metabolizing enzymes and transporters, and the identification of these underlying mechanisms would help physicians and patients to predict, detect and prevent DDIs...
July 30, 2018: Current Drug Metabolism
Mohamed Abouzid, Marta Karazniewicz-Lada, Franciszek Glowka
The endocrine system of vitamin D is involved in an extensive variety of biological processes such as bone metabolism, regulation of cell proliferation and differentiation and modulation of the immune response. The active form of vitamin D, 25-hydroxyvitamin D, binds to vitamin D receptor (VDR) controlling the synthesis of many different proteins. Although numerous studies reported polymorphism in the VDR gene, the impact of the polymorphic alleles on VDR protein function remains unknown. BsmI, ApaI, and TaqI are the three adjacent single nucleotide polymorphisms in intron 8/exon nine at the 3' end of the VDR gene which have been most frequently studied so far...
July 23, 2018: Current Drug Metabolism
Zarith Asyikin Abdul Aziz, Akil Ahmad, Siti Hamidah Mohd Setapar, Alptug Karakucuk, Muhammad Mohsin Azim, David Lokhat, Mohammad Amjad Kamal, Ghulam Md Ashraf
BACKGROUND: Essential oils are liquid extracts from aromatic plants, which have numerous applications in multiple industries. There are a variety of methods used for the extraction of essential oils, with each method exhibiting certain advantages and determining the biological and physicochemical properties of the extacted oils. Essential oils from different plant species contain more than 200 constituents which are comprised of volatile and non-volatile components. The application of essential oils as antimicrobial, anticancer, anti-inflammatory and anti-viral agents are due to their effective and efficient properties, inter alia...
July 23, 2018: Current Drug Metabolism
Mo'tasem M Alsmadi, Nasir Idkaidek
BACKGROUND: Clinical studies during pregnancy are rare due to ethical and practical limitations. Giving pregnant females the same dosing regimen used in adult males or nonpregnant females is inappropriate. Pregnancy physiologically-based pharmacokinetic modeling is a powerful tool that can be used to refine pharmacotherapy during pregnancy. OBJECTIVE: This work provides a review of the current status of application of physiologically based pharmacokinetic models in developing dosing regimens in pregnant women...
July 1, 2018: Current Drug Metabolism
Negiin Pourafshar, Saeed Alshahrani, Ashkan Karimi, Manoocher Soleimani
Thiazides are the most commonly used medications for the treatment of mild and moderate hypertension. Despite their recognized effect, the mechanism by which thiazides reduce systemic blood pressure remains uncertain. The prevailing belief is that thiazides reduce blood pressure primarily via enhancement of salt excretion consequent to the inhibition of the Na-Cl cotransporter (NCC) in the distal convoluted tubules (DCT). However, recent reports point to a reduction in peripheral vascular resistance as a major mechanism of anti-hypertensive effect of thiazides...
July 1, 2018: Current Drug Metabolism
Joana Goncalves, Joana Bicker, Gilberto Alves, Ana Fortuna, Amilcar Falcao
BACKGROUND: Breast cancer resistance protein (BCRP, also known as ABCG2) is gaining momentum as a key transporter that restricts the permeability of a large number of therapeutic agents through the blood-brain barrier (BBB). BCRP is highly expressed in the apical membranes of epithelial cells of the small and large intestine, renal proximal tubules and canalicular membrane of hepatocytes, determining the gastrointestinal absorption and biodisposition of its substrates. It is also expressed in the luminal surface of endothelial cells of the BBB and blood-spinal cord barrier (BSCB), where it undoubtedly limits the entry of a wide range of therapeutics into the CNS, potentially contributing to the therapeutic failure of CNS-acting drugs...
June 29, 2018: Current Drug Metabolism
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