1,008 results match your criteria Medicinal Research Reviews[Journal]


Gut microbiome interventions in human health and diseases.

Med Res Rev 2019 Apr 17. Epub 2019 Apr 17.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China.

Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Read More

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http://dx.doi.org/10.1002/med.21584DOI Listing

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives.

Med Res Rev 2019 Apr 11. Epub 2019 Apr 11.

Department of Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Read More

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http://dx.doi.org/10.1002/med.21580DOI Listing
April 2019
1 Read
8.431 Impact Factor

Emerging roles of allosteric modulators in the regulation of protein-protein interactions (PPIs): A new paradigm for PPI drug discovery.

Med Res Rev 2019 Apr 7. Epub 2019 Apr 7.

Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Clinical and Fundamental Research Center, Renji Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China.

Protein-protein interactions (PPIs) are closely implicated in various types of cellular activities and are thus pivotal to health and disease states. Given their fundamental roles in a wide range of biological processes, the modulation of PPIs has enormous potential in drug discovery. However, owing to the general properties of large, flat, and featureless interfaces of PPIs, previous attempts have demonstrated that the generation of therapeutic agents targeting PPI interfaces is challenging, rendering them almost "undruggable" for decades. Read More

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http://dx.doi.org/10.1002/med.21585DOI Listing
April 2019
8.431 Impact Factor

The emergence of melatonin in oncology: Focus on colorectal cancer.

Med Res Rev 2019 Apr 4. Epub 2019 Apr 4.

Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain.

Within the last few decades, melatonin has increasingly emerged in clinical oncology as a naturally occurring bioactive molecule with substantial anticancer properties and a pharmacological profile optimal for joining the currently available pharmacopeia. In addition, extensive experimental data shows that this chronobiotic agent exerts oncostatic effects throughout all stages of tumor growth, from initial cell transformation to mitigation of malignant progression and metastasis; additionally, melatonin alleviates the side effects and improves the welfare of radio/chemotherapy-treated patients. Thus, the support of clinicians and oncologists for the use of melatonin in both the treatment and proactive prevention of cancer is gaining strength. Read More

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http://dx.doi.org/10.1002/med.21582DOI Listing

The A-B-C of small-molecule ABC transport protein modulators: From inhibition to activation-a case study of multidrug resistance-associated protein 1 (ABCC1).

Med Res Rev 2019 Apr 3. Epub 2019 Apr 3.

Pharmaceutical Institute, Rheinische Friedrich-Wilhelms-University of Bonn, Bonn, Germany.

Several mechanisms of pharmacokinetic, metabolic, and regulatory nature have been elucidated to take part or act in concert in the phenomenon of multidrug resistance (MDR). MDR is characterized by cross-resistance of cells against chemotherapeutic agents, which are used for treatment of e.g. Read More

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http://dx.doi.org/10.1002/med.21573DOI Listing
April 2019
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A review of the molecular design and biological activities of RXR agonists.

Med Res Rev 2019 Apr 3. Epub 2019 Apr 3.

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska.

An attractive approach to combat disease is to target theregulation of cell function. At the heart of this task are nuclear receptors (NRs); which control functions such as gene transcription. Arguably, the key player in this regulatory machinery is the retinoid X receptor (RXR). Read More

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http://dx.doi.org/10.1002/med.21578DOI Listing

Understanding the riboflavin biosynthesis pathway for the development of antimicrobial agents.

Med Res Rev 2019 Mar 29. Epub 2019 Mar 29.

Department of Organic and Medicinal Chemistry, CSIR-Indian Institute of Chemical Biology, Kolkata, India.

Life on earth depends on the biosynthesis of riboflavin, which plays a vital role in biological electron transport processes. Higher mammals obtain riboflavin from dietary sources; however, various microorganisms, including Gram-negative pathogenic bacteria and yeast, lack an efficient riboflavin-uptake system and are dependent on endogenous riboflavin biosynthesis. Consequently, the inhibition of enzymes in the riboflavin biosynthesis pathway would allow selective toxicity to a pathogen and not the host. Read More

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http://dx.doi.org/10.1002/med.21576DOI Listing

ETS transcription factors as emerging drug targets in cancer.

Med Res Rev 2019 Mar 29. Epub 2019 Mar 29.

Vancouver Prostate Centre and the Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

The ETS family of proteins consists of 28 transcription factors, many of which have been implicated in development and progression of a variety of cancers. While one family member, ERG, has been rigorously studied in the context of prostate cancer where it plays a critical role, other ETS factors keep emerging as potential hallmark oncodrivers. In recent years, numerous studies have reported initial discoveries of small molecule inhibitors of ETS proteins and opened novel avenues for ETS-directed cancer therapies. Read More

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http://dx.doi.org/10.1002/med.21575DOI Listing

JNK signaling in cancer cell survival.

Med Res Rev 2019 Mar 25. Epub 2019 Mar 25.

Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic.

c-Jun N-terminal kinase (JNK) is involved in cancer cell apoptosis; however, emerging evidence indicates that this Janus signaling promotes cancer cell survival. JNK acts synergistically with NF-κB, JAK/STAT, and other signaling molecules to exert a survival function. JNK positively regulates autophagy to counteract apoptosis, and its effect on autophagy is related to the development of chemotherapeutic resistance. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/med.21574
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http://dx.doi.org/10.1002/med.21574DOI Listing
March 2019
5 Reads

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review.

Med Res Rev 2019 Mar 19. Epub 2019 Mar 19.

Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

Bacteriophages are not forgotten viruses anymore: scientists and practitioners seek to understand phage pharmacokinetics in animals and humans, investigating bacteriophages as therapeutics, nanocarriers or microbiome components. This review provides a comprehensive overview of factors that determine phage circulation, penetration, and clearance, and that in consequence determine phage applicability for medicine. It makes use of experimental data collected by the phage community so far (PubMed 1924-2016, including non-English reports), combining elements of critical and systematic review. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/med.21572
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http://dx.doi.org/10.1002/med.21572DOI Listing
March 2019
2 Reads

Modulation of autophagy in human diseases strategies to foster strengths and circumvent weaknesses.

Med Res Rev 2019 Feb 28. Epub 2019 Feb 28.

Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.

Autophagy is central to the maintenance of intracellular homeostasis across species. Accordingly, autophagy disorders are linked to a variety of diseases from the embryonic stage until death, and the role of autophagy as a therapeutic target has been widely recognized. However, autophagy-associated therapy for human diseases is still in its infancy and is supported by limited evidence. Read More

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http://dx.doi.org/10.1002/med.21571DOI Listing
February 2019

Dimethyl fumarate, a two-edged drug: Current status and future directions.

Med Res Rev 2019 Feb 12. Epub 2019 Feb 12.

Department of Development, Reproduction and Cancer, Paris Descartes University, Sorbonne Paris Cité, INSERM U1016, Cochin Institute, CARPEM, Paris, France.

Dimethyl fumarate (DMF) is a fumaric acid ester registered for the treatment of relapsing-remitting multiple sclerosis (RRMS). It induces protein succination leading to inactivation of cysteine-rich proteins. It was first shown to possess cytoprotective and antioxidant effects in noncancer models, which appeared related to the induction of the nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) pathway. Read More

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http://dx.doi.org/10.1002/med.21567DOI Listing
February 2019
3 Reads

Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy.

Med Res Rev 2019 Feb 11. Epub 2019 Feb 11.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee.

Microtubule (MT)-targeting agents are highly successful drugs as chemotherapeutic agents, and this is attributed to their ability to target MT dynamics and interfere with critical cellular functions, including, mitosis, cell signaling, intracellular trafficking, and angiogenesis. Because MT dynamics vary in the different stages of the cell cycle, these drugs tend to be the most effective against mitotic cells. While this class of drug has proven to be effective against many cancer types, significant hurdles still exist and include overcoming aspects such as dose limited toxicities and the development of resistance. Read More

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http://dx.doi.org/10.1002/med.21568DOI Listing
February 2019
1 Read
8.431 Impact Factor

Health benefits of resveratrol: Evidence from clinical studies.

Med Res Rev 2019 Feb 11. Epub 2019 Feb 11.

Laboratory for Translational Cancer Research, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, India.

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. Read More

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http://doi.wiley.com/10.1002/med.21565
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http://dx.doi.org/10.1002/med.21565DOI Listing
February 2019
9 Reads
8.431 Impact Factor

Imaging metabotropic glutamate receptor system: Application of positron emission tomography technology in drug development.

Med Res Rev 2019 Feb 10. Epub 2019 Feb 10.

Pharmaceutical Research and Development, SOFIE Biosciences, Somerset, New Jersey.

The diversity seen in the mode of pharmacology and the numerous glutamate receptor subtypes have previously complicated drug development efforts. Nonetheless, recent clinical trials of drug candidates that accommodate the glutamatergic intricate pharmacology have yielded encouraging results. Target engagement is an important requirement for the advancement of central nervous system drug candidates into clinical trial. Read More

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http://dx.doi.org/10.1002/med.21566DOI Listing
February 2019
4 Reads

Alternative oxidase inhibitors: Mitochondrion-targeting as a strategy for new drugs against pathogenic parasites and fungi.

Med Res Rev 2019 Jan 29. Epub 2019 Jan 29.

Instituto de Química Médica, IQM-CSIC, Madrid, Spain.

The alternative oxidase (AOX) is a ubiquitous terminal oxidase of plants and many fungi, catalyzing the four-electron reduction of oxygen to water alongside the cytochrome-based electron transfer chain. Unlike the classical electron transfer chain, however, the activity of AOX does not generate adenosine triphosphate but has functions such as thermogenesis and stress response. As it lacks a mammalian counterpart, it has been investigated intensely in pathogenic fungi. Read More

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http://doi.wiley.com/10.1002/med.21560
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http://dx.doi.org/10.1002/med.21560DOI Listing
January 2019
6 Reads
8.431 Impact Factor

Intramolecular hydrogen bonding: An opportunity for improved design in medicinal chemistry.

Med Res Rev 2019 Jan 19. Epub 2019 Jan 19.

Molecular Biotechnology and Health Sciences Department, University of Torino, Torino, Italy.

Recent literature shows that intramolecular hydrogen bond (IMHB) formation can positively impact upon the triad of permeability, solubility, and potency of drugs and candidates. IMHB modulation can be applied to compounds in any chemical space as a means for discovering drug candidates with both acceptable potency and absorption, distribution, metabolism, and excretion-Tox profiles. Integrating IMHB formation in design of drugs is, therefore, an exciting and timely challenge for modern medicinal chemistry. Read More

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http://dx.doi.org/10.1002/med.21562DOI Listing
January 2019
2 Reads

Rhodiola species: A comprehensive review of traditional use, phytochemistry, pharmacology, toxicity, and clinical study.

Med Res Rev 2019 Jan 16. Epub 2019 Jan 16.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.

Rhodiola species, belonging to the family Crassulaceae, have long been used as an adaptogen, tonic, antidepressant, and antistress medicine or functional food in Asia and Europe. Due to the valuable application, the growing demand of Rhodiola species has led to a rapid decrease in resource content. This review aims to summarize the integrated research progress of seven mainstream Rhodiola species. Read More

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http://doi.wiley.com/10.1002/med.21564
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http://dx.doi.org/10.1002/med.21564DOI Listing
January 2019
5 Reads
8.431 Impact Factor

Antiaging effects of bioactive molecules isolated from plants and fungi.

Med Res Rev 2019 Jan 15. Epub 2019 Jan 15.

Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China.

Aging is influenced by many lifestyle choices that are under human control, including nutrition and exercise. The most effective known antiaging intervention consists of calorie restriction (CR), which increases lifespan in yeasts, worms, fruit flies, mice, and nonhuman primates. CR also improves healthspan by preventing the development of various aging-related diseases such as cancer, cardiovascular disease, diabetes, and neurodegeneration. Read More

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http://dx.doi.org/10.1002/med.21559DOI Listing
January 2019
2 Reads
8.431 Impact Factor

Multidisciplinary approaches for targeting the secretase protein family as a therapeutic route for Alzheimer's disease.

Med Res Rev 2019 Jan 9. Epub 2019 Jan 9.

Faculty of Medical Technology, Center of Data Mining and Biomedical Informatics, Mahidol University, Bangkok, Thailand.

The continual increase of the aging population worldwide renders Alzheimer's disease (AD) a global prime concern. Several attempts have been focused on understanding the intricate complexity of the disease's development along with the on- andgoing search for novel therapeutic strategies. Incapability of existing AD drugs to effectively modulate the pathogenesis or to delay the progression of the disease leads to a shift in the paradigm of AD drug discovery. Read More

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http://dx.doi.org/10.1002/med.21563DOI Listing
January 2019
1 Read

Monoamine oxidase-B inhibitors as potential neurotherapeutic agents: An overview and update.

Med Res Rev 2019 Jan 2. Epub 2019 Jan 2.

Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, India.

Monoamine oxidase (MAO) inhibitors have made significant contributions and remain an indispensable approach of molecular and mechanistic diversity for the discovery of antineurodegenerative drugs. However, their usage has been hampered by nonselective and/or irreversible action which resulted in drawbacks like liver toxicity, cheese effect, and so forth. Hence, the search for selective MAO inhibitors (MAOIs) has become a substantial focus in current drug discovery. Read More

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http://dx.doi.org/10.1002/med.21561DOI Listing
January 2019
2 Reads

Norovirus antivirals: Where are we now?

Med Res Rev 2019 05 25;39(3):860-886. Epub 2018 Dec 25.

School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, New South Wales, Australia.

Human noroviruses inflict a significant health burden on society and are responsible for approximately 699 million infections and over 200 000 estimated deaths worldwide each year. Yet despite significant research efforts, approved vaccines or antivirals to combat this pathogen are still lacking. Safe and effective antivirals are not available, particularly for chronically infected immunocompromised individuals, and for prophylactic applications to protect high-risk and vulnerable populations in outbreak settings. Read More

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http://doi.wiley.com/10.1002/med.21545
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http://dx.doi.org/10.1002/med.21545DOI Listing
May 2019
14 Reads

A magic drug target: Androgen receptor.

Med Res Rev 2018 Dec 19. Epub 2018 Dec 19.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.

Androgen receptor (AR) is closely associated with a group of hormone-related diseases including the cancers of prostate, breast, ovary, pancreas, etc and anabolic deficiencies such as muscle atrophy and osteoporosis. Depending on the specific type and stage of the diseases, AR ligands including not only antagonists but also agonists and modulators are considered as potential therapeutics, which makes AR an extremely interesting drug target. Here, we at first review the current understandings on the structural characteristics of AR, and then address why and how AR is investigated as a drug target for the relevant diseases and summarize the representative antagonists and agonists targeting five prospective small molecule binding sites at AR, including ligand-binding pocket, activation function-2 site, binding function-3 site, DNA-binding domain, and N-terminal domain, providing recent insights from a target and drug development view. Read More

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http://doi.wiley.com/10.1002/med.21558
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http://dx.doi.org/10.1002/med.21558DOI Listing
December 2018
18 Reads

Molecules targeting the androgen receptor (AR) signaling axis beyond the AR-Ligand binding domain.

Med Res Rev 2019 05 22;39(3):910-960. Epub 2018 Nov 22.

Department of Chemistry and Biochemistry, UCLA, Los Angeles, California.

Prostate cancer (PCa) is the second most common cause of cancer-related mortality in men in the United States. The androgen receptor (AR) and the physiological pathways it regulates are central to the initiation and progression of PCa. As a member of the nuclear steroid receptor family, it is a transcription factor with three distinct functional domains (ligand-binding domain [LBD], DNA-binding domain [DBD], and transactivation domain [TAD]) in its structure. Read More

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http://dx.doi.org/10.1002/med.21548DOI Listing

Harnessing the untapped potential of nucleotide-binding oligomerization domain ligands for cancer immunotherapy.

Med Res Rev 2018 Dec 13. Epub 2018 Dec 13.

University of Ljubljana, Faculty of Pharmacy, Ljubljana, Slovenia.

In the last decade, cancer immunotherapy has emerged as an effective alternative to traditional therapies such as chemotherapy and radiation. In contrast to the latter, cancer immunotherapy has the potential to distinguish between cancer and healthy cells, and thus to avoid severe and intolerable side-effects, since the cancer cells are effectively eliminated by stimulated immune cells. The cytosolic nucleotide-binding oligomerization domains 1 and 2 receptors (NOD1 and NOD2) are important components of the innate immune system and constitute interesting targets in terms of strengthening the immune response against cancer cells. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/med.21557
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December 2018
14 Reads

Evolution of efficacious pangenotypic hepatitis C virus therapies.

Med Res Rev 2019 05 2;39(3):1091-1136. Epub 2018 Dec 2.

Biomedical Informatics Research Laboratory, Department of Biology, Lahore University of Management Sciences, Lahore, Pakistan.

Hepatitis C compromises the quality of life of more than 350 million individuals worldwide. Over the last decade, therapeutic regimens for treating hepatitis C virus (HCV) infections have undergone rapid advancements. Initially, structure-based drug design was used to develop molecules that inhibit viral enzymes. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/med.21554
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May 2019
21 Reads
8.431 Impact Factor

Design of Hedgehog pathway inhibitors for cancer treatment.

Med Res Rev 2019 05 28;39(3):1137-1204. Epub 2018 Nov 28.

Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska.

Hedgehog (Hh) signaling is involved in the initiation and progression of various cancers and is essential for embryonic and postnatal development. This pathway remains in the quiescent state in adult tissues but gets activated upon inflammation and injuries. Inhibition of Hh signaling pathway using natural and synthetic compounds has provided an attractive approach for treating cancer and inflammatory diseases. Read More

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http://doi.wiley.com/10.1002/med.21555
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http://dx.doi.org/10.1002/med.21555DOI Listing
May 2019
18 Reads

Development and therapeutic potential of autotaxin small molecule inhibitors: From bench to advanced clinical trials.

Med Res Rev 2019 05 21;39(3):976-1013. Epub 2018 Nov 21.

Division of Immunology, Biomedical Sciences Research Center "Alexander Fleming", Athens, Greece.

Several years after its isolation from melanoma cells, an increasing body of experimental evidence has established the involvement of Autotaxin (ATX) in the pathogenesis of several diseases. ATX, an extracellular enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) into the bioactive lipid lysophosphatidic acid (LPA), is overexpressed in a variety of human metastatic cancers and is strongly implicated in chronic inflammation and liver toxicity, fibrotic diseases, and thrombosis. Accordingly, the ATX-LPA signaling pathway is considered a tractable target for therapeutic intervention substantiated by the multitude of research campaigns that have been successful in identifying ATX inhibitors by both academia and industry. Read More

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http://dx.doi.org/10.1002/med.21551DOI Listing
May 2019
18 Reads

Topoisomerase 1B poisons: Over a half-century of drug leads, clinical candidates, and serendipitous discoveries.

Authors:
Maris A Cinelli

Med Res Rev 2018 Nov 19. Epub 2018 Nov 19.

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan.

Topoisomerases are DNA processing enzymes that relieve supercoiling (torsional strain) in DNA, are necessary for normal cellular division, and act by nicking (and then religating) DNA strands. Type 1B topoisomerase (Top1) is overexpressed in certain tumors, and the enzyme has been extensively investigated as a target for cancer chemotherapy. Various chemical agents can act as "poisons" of the enzyme's religation step, leading to Top1-DNA lesions, DNA breakage, and eventual cellular death. Read More

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http://dx.doi.org/10.1002/med.21546DOI Listing
November 2018
12 Reads

Recent clinical trends in Toll-like receptor targeting therapeutics.

Med Res Rev 2019 05 18;39(3):1053-1090. Epub 2018 Nov 18.

Department of Molecular Science and Technology, Ajou University, Suwon, Korea.

Toll-like receptors (TLRs) are germline-encoded receptors that are central to innate and adaptive immune responses. Owing to their vital role in inflammation, TLRs are rational targets in clinics; thus, many ligands and biologics have been reported to overcome the progression of various inflammatory and malignant conditions and support the immune system. For each TLR, at least one, and often many, drug formulations are being evaluated. Read More

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http://doi.wiley.com/10.1002/med.21553
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May 2019
19 Reads

Hunting for the high-affinity state of G-protein-coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging.

Med Res Rev 2019 05 18;39(3):1014-1052. Epub 2018 Nov 18.

Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

The concept of the high-affinity state postulates that a certain subset of G-protein-coupled receptors is primarily responsible for receptor signaling in the living brain. Assessing the abundance of this subset is thus potentially highly relevant for studies concerning the responses of neurotransmission to pharmacological or physiological stimuli and the dysregulation of neurotransmission in neurological or psychiatric disorders. The high-affinity state is preferentially recognized by agonists in vitro. Read More

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http://doi.wiley.com/10.1002/med.21552
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May 2019
12 Reads

Orexin supplementation in narcolepsy treatment: A review.

Med Res Rev 2019 05 14;39(3):961-975. Epub 2018 Nov 14.

Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czech Republic.

Narcolepsy is a rare, chronic neurological disease characterized by excessive daytime sleepiness, cataplexy, vivid hallucinations, and sleep paralysis. Narcolepsy occurs in approximately 1 of 3000 people, affecting mainly adolescents aged 15 to 30 years. Recently, people with narcolepsy were shown to exhibit extensive orexin/hypocretin neuronal loss. Read More

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http://doi.wiley.com/10.1002/med.21550
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May 2019
36 Reads

Therapeutic strategies involving survivin inhibition in cancer.

Med Res Rev 2019 05 12;39(3):887-909. Epub 2018 Nov 12.

Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona, Barcelona, Spain.

Survivin is a small protein that belongs to the inhibitor of apoptosis protein family. It is abundantly expressed in tumors compared with adult differentiated tissues, being associated with poor prognosis in many human neoplasms. This apoptotic inhibitor has a relevant role in both the promotion of cancer cell survival and in the inhibition of cell death. Read More

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http://doi.wiley.com/10.1002/med.21547
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May 2019
16 Reads

Dynamic genome and transcriptional network-based biomarkers and drugs: precision in breast cancer therapy.

Med Res Rev 2019 05 11;39(3):1205-1227. Epub 2018 Nov 11.

Centre for Biosystems and Genome Network Medicine, Ioannina University, Ioannina, Greece.

Despite remarkable progress in medium-term overall survival benefit in the adjuvant, neoadjuvant and metastatic settings, with multiple recent targeted drug approvals, acquired resistance, late relapse, and cancer-related death rates remain challenging. Integrated technological systems have been developed to overcome these unmet needs. The characterization of structural and functional noncoding genome elements through next-generation sequencing (NGS) systems, Hi-C and CRISPR/Cas9, as well as computational models, allows for whole genome and transcriptome analysis. Read More

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http://dx.doi.org/10.1002/med.21549DOI Listing

Challenges and approaches in the discovery of human immunodeficiency virus type-1 non-nucleoside reverse transcriptase inhibitors.

Med Res Rev 2018 Nov 11. Epub 2018 Nov 11.

Laboratorio de Química Medicinal, Centro de Investigaciones en Bionanociencias (CIBION), CONICET, Ciudad de Buenos Aires, Argentina.

The type I human immunodeficiency virus (HIV-1) pandemic affecting over 37 million people worldwide continues, with 1.8 million people newly infected each year. Highly active antiretroviral therapy is efficient at reducing viral load and nearly one-half of the infected population is on treatment. Read More

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http://doi.wiley.com/10.1002/med.21544
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November 2018
8 Reads

Antitubulin sulfonamides: The successful combination of an established drug class and a multifaceted target.

Med Res Rev 2019 05 25;39(3):775-830. Epub 2018 Oct 25.

Laboratorio de Química Orgánica y Farmacéutica, Departamento de Ciencias Farmacéuticas, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain.

Tubulin, the microtubules and their dynamic behavior are amongst the most successful antitumor, antifungal, antiparasitic, and herbicidal drug targets. Sulfonamides are exemplary drugs with applications in the clinic, in veterinary and in the agrochemical industry. This review summarizes the actual state and recent progress of both fields looking from the double point of view of the target and its drugs, with special focus onto the structural aspects. Read More

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http://dx.doi.org/10.1002/med.21541DOI Listing

Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era.

Med Res Rev 2019 05 24;39(3):831-859. Epub 2018 Oct 24.

Institute of Animal Nutrition, Department of Animal Nutrition, Northeast Agricultural University, Harbin, China.

Antimicrobial peptides (AMPs), critical components of the innate immune system, are widely distributed throughout the animal and plant kingdoms. They can protect against a broad array of infection-causing agents, such as bacteria, fungi, parasites, viruses, and tumor cells, and also exhibit immunomodulatory activity. AMPs exert antimicrobial activities primarily through mechanisms involving membrane disruption, so they have a lower likelihood of inducing drug resistance. Read More

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http://dx.doi.org/10.1002/med.21542DOI Listing

Therapeutic potential of pteridine derivatives: A comprehensive review.

Med Res Rev 2019 03 19;39(2):461-516. Epub 2018 Oct 19.

Departamento de Bioquímica, Biología Molecular (B) e Inmunología, Facultad de Medicina, IMIB and Regional Campus of International Excellence "Campus Mare Nostrum," Universidad de Murcia, Murcia, Spain.

Pteridines are aromatic compounds formed by fused pyrazine and pyrimidine rings. Many living organisms synthesize pteridines, where they act as pigments, enzymatic cofactors, or immune system activation molecules. This variety of biological functions has motivated the synthesis of a huge number of pteridine derivatives with the aim of studying their therapeutic potential. Read More

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http://dx.doi.org/10.1002/med.21529DOI Listing
March 2019
1 Read

Lipidic prodrug approach for improved oral drug delivery and therapy.

Med Res Rev 2019 03 15;39(2):579-607. Epub 2018 Oct 15.

Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

In the past, a prodrug design was used as a last option to improve bioavailability through controlling transport, distribution, metabolism, or other mechanisms. Prodrugs are currently used even in early stages of drug development, and a significant percentage of all drugs in the market are prodrugs. The focus of this article is lipidic prodrugs, a strategy whereby a lipid carrier is covalently bound to the drug moiety. Read More

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http://doi.wiley.com/10.1002/med.21533
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http://dx.doi.org/10.1002/med.21533DOI Listing
March 2019
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Recent structural advances in constrained helical peptides.

Med Res Rev 2019 03 11;39(2):749-770. Epub 2018 Oct 11.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois.

Given the ubiquity of the ⍺-helix in the proteome, there has been much research in developing mimics of ⍺-helices, and most of this study has been toward developing protein-protein interaction inhibitors. A common strategy for mimicking ⍺-helices has been through the use of constrained, helical peptides. The addition of a constraint typically provides for conformational and proteolytic stability and, in some cases, cell permeability. Read More

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http://doi.wiley.com/10.1002/med.21540
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http://dx.doi.org/10.1002/med.21540DOI Listing
March 2019
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The multifaceted role of autophagy in cancer and the microenvironment.

Med Res Rev 2019 03 9;39(2):517-560. Epub 2018 Oct 9.

Department of Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Autophagy is a crucial recycling process that is increasingly being recognized as an important factor in cancer initiation, cancer (stem) cell maintenance as well as the development of resistance to cancer therapy in both solid and hematological malignancies. Furthermore, it is being recognized that autophagy also plays a crucial and sometimes opposing role in the complex cancer microenvironment. For instance, autophagy in stromal cells such as fibroblasts contributes to tumorigenesis by generating and supplying nutrients to cancerous cells. Read More

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http://dx.doi.org/10.1002/med.21531DOI Listing

Roles of microRNAs in T cell immunity: Implications for strategy development against infectious diseases.

Med Res Rev 2019 03 11;39(2):706-732. Epub 2018 Sep 11.

Key Laboratory of Animal Parasitology of Ministry of Agriculture, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.

T cell immunity plays a vital role in pathogen infections. MicroRNA (miRNAs) are small, single-stranded noncoding RNAs that regulate T cell immunity by targeting key transcriptional factors, signaling proteins, and cytokines associated with T cell activation, differentiation, and function. The dysregulation of miRNA expression in T cells may lead to specific immune responses and can provide new therapeutic opportunities against various infectious diseases. Read More

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http://dx.doi.org/10.1002/med.21539DOI Listing

Involvement of calpain in the neuropathogenesis of Alzheimer's disease.

Med Res Rev 2019 03 10;39(2):608-630. Epub 2018 Sep 10.

Department of Pathophysiology, Key Laboratory of Education Ministry of China for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Alzheimer's disease (AD) is the most common (60% to 80%) age-related disease associated with dementia and is characterized by a deterioration of behavioral and cognitive capacities leading to death in few years after diagnosis, mainly due to complications from chronic illness. The characteristic hallmarks of the disease are extracellular senile plaques (SPs) and intracellular neurofibrillary tangles (NFTs) with neuropil threads, which are a direct result of amyloid precursor protein (APP) processing to Aβ, and τ hyperphosphorylation. However, many indirect underlying processes play a role in this event. Read More

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http://dx.doi.org/10.1002/med.21534DOI Listing
March 2019
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Mechanistic/mammalian target of rapamycin: Recent pathological aspects and inhibitors.

Med Res Rev 2019 03 24;39(2):631-664. Epub 2018 Sep 24.

Center for Biomaterials, Korea Institute of Science and Technology, Seoul, Korea.

The mechanistic/mammalian target of rapamycin (mTOR), also known as the mechanistic target of rapamycin, regulates many normal cell processes such as transcription, cell growth, and autophagy. Overstimulation of mTOR by its ligands, amino acids, sugars, and/or growth factors leads to physiological disorders, including cancer and neurodegenerative diseases. In this study, we reviewed the recent advances regarding the mechanism that involves mTOR in cancer, aging, and neurodegenerative diseases. Read More

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http://dx.doi.org/10.1002/med.21535DOI Listing
March 2019
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Immunomodulators targeting the PD-1/PD-L1 protein-protein interaction: From antibodies to small molecules.

Med Res Rev 2019 01 14;39(1):265-301. Epub 2018 Sep 14.

Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.

Cancer immunotherapy has made great strides in the recent decade, especially in the area of immune checkpoint blockade. The outstanding efficacy, prolonged durability of effect, and rapid assimilation of anti-PD-1 and anti-PD-L1 monoclonal antibodies in clinical practice have been nothing short of a medical breakthrough in the treatment of numerous malignancies. The major advantages of these therapeutic antibodies over their small molecule counterparts have been their high binding affinity and target specificity. Read More

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http://dx.doi.org/10.1002/med.21530DOI Listing
January 2019
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Chemical space of Escherichia coli dihydrofolate reductase inhibitors: New approaches for discovering novel drugs for old bugs.

Med Res Rev 2019 03 7;39(2):684-705. Epub 2018 Sep 7.

Center for the Study of Systems Biology, School of Biology, Georgia Institute of Technology, Atlanta, Georgia.

Escherichia coli Dihydrofolate reductase is an important enzyme that is essential for the survival of the Gram-negative microorganism. Inhibitors designed against this enzyme have demonstrated application as antibiotics. However, either because of poor bioavailability of the small-molecules resulting from their inability to cross the double membrane in Gram-negative bacteria or because the microorganism develops resistance to the antibiotics by mutating the DHFR target, discovery of new antibiotics against the enzyme is mandatory to overcome drug-resistance. Read More

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http://dx.doi.org/10.1002/med.21538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370515PMC
March 2019
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8.431 Impact Factor

Polyphenolic natural products and natural product-inspired steroidal mimics as aromatase inhibitors.

Med Res Rev 2018 Sep 1. Epub 2018 Sep 1.

Department of Chemistry & Chemical Biology, McMaster University, Hamilton, Ontario, Canada.

The discovery of biologically active polyphenolic natural products, including chalcones, stilbenes, flavanones, and isoflavones as steroidal mimics has proven to be a subject of considerable importance in medicine. Some of these natural compounds have been shown to modulate key human metabolic processes via steroidal hormone receptors, or to inhibit crucial enzymes involved in the biosynthesis of steroidal hormones themselves. Isoflavone polyphenolics such as genistein are well known for this "phytoestrogenic" biological activity. Read More

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http://doi.wiley.com/10.1002/med.21536
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http://dx.doi.org/10.1002/med.21536DOI Listing
September 2018
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Progress in the application of CRISPR: From gene to base editing.

Med Res Rev 2019 03 1;39(2):665-683. Epub 2018 Sep 1.

Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts.

The system of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated endonucleases (Cas) has been utilized for genome editing with great accuracy and high efficiency in generating gene knockout, knockin, and point mutations in eukaryotic genomes. However, traditional CRISPR/Cas9 technology introduces double-stranded DNA breaks (DSBs) at a target locus as the first step to make gene corrections, which easily results in undesired mutations. Thus, it is necessary to develop new methods for correcting the unwanted mutations. Read More

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http://dx.doi.org/10.1002/med.21537DOI Listing
March 2019
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Targeting strategies for drug delivery to the kidney: From renal glomeruli to tubules.

Med Res Rev 2019 03 22;39(2):561-578. Epub 2018 Aug 22.

Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Kidney diseases have become a global public health problem. The application of kidney-targeted drug-delivery systems in the management of kidney diseases has profound transformative potential. Kidney-targeted drug delivery can reduce the undesired side effects of often potent drugs and enhance drug efficacy in alleviating the kidney disease. Read More

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http://dx.doi.org/10.1002/med.21532DOI Listing
March 2019
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Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs.

Med Res Rev 2019 03 12;39(2):733-748. Epub 2018 Aug 12.

Center of Physiology, Georg-August University, Goettingen, Germany.

Over the past decades, a multitude of experimental drugs have been shown to delay disease progression in preclinical animal models of amyotrophic lateral sclerosis (ALS) but failed to show efficacy in human clinical trials or are still waiting for approval under Phase I-III trials. Riluzole, a glutamatergic neurotransmission inhibitor, is the only drug approved by the USA Food and Drug Administration for ALS treatment with modest benefits on survival. Recently, an antioxidant drug, edaravone, developed by Mitsubishi Tanabe Pharma was found to be effective in halting ALS progression during early stages. Read More

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http://doi.wiley.com/10.1002/med.21528
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March 2019
67 Reads