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Medicinal Research Reviews

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https://read.qxmd.com/read/30756407/dimethyl-fumarate-a-two-edged-drug-current-status-and-future-directions
#1
REVIEW
Nathaniel Edward Bennett Saidu, Niloufar Kavian, Karen Leroy, Claus Jacob, Carole Nicco, Frédéric Batteux, Jérôme Alexandre
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. DMF also displays antitumor activity in several cellular and mice models. Recently, we showed that the anticancer mechanism of DMF is dose-dependent and is paradoxically related to the decrease in the nuclear translocation of NRF2...
February 12, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30746734/current-advances-of-tubulin-inhibitors-as-dual-acting-small-molecules-for-cancer-therapy
#2
REVIEW
Kinsie E Arnst, Souvik Banerjee, Hao Chen, Shanshan Deng, Dong-Jin Hwang, Wei Li, Duane D Miller
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...
February 11, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30741437/health-benefits-of-resveratrol-evidence-from-clinical-studies
#3
REVIEW
Akhand Pratap Singh, Rachna Singh, Sumit Singh Verma, Vipin Rai, Catherine H Kaschula, Pralay Maiti, Subash Chandra Gupta
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...
February 11, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30740744/imaging-metabotropic-glutamate-receptor-system-application-of-positron-emission-tomography-technology-in-drug-development
#4
REVIEW
Youwen Xu, Zizhong Li
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. Positron emission tomography (PET) tracer technology has the unique ability to give the direct insight into the relationship between the level of receptor occupancy and the administered dose, thus establishing a direct link between the level of target exposure and the drug efficacy in human...
February 10, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30693533/alternative-oxidase-inhibitors-mitochondrion-targeting-as-a-strategy-for-new-drugs-against-pathogenic-parasites-and-fungi
#5
REVIEW
Godwin U Ebiloma, Emmanuel O Balogun, Eduardo J Cueto-Díaz, Harry P de Koning, Christophe Dardonville
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. However, it is in African trypanosomes, which lack cytochrome-based respiration in their infective stages, that trypanosome alternative oxidase (TAO) plays the central and essential role in their energy metabolism...
January 29, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30659634/intramolecular-hydrogen-bonding-an-opportunity-for-improved-design-in-medicinal-chemistry
#6
REVIEW
Giulia Caron, Jan Kihlberg, Giuseppe Ermondi
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. In this review, we first provide some background about IMHBs from the medicinal chemist's point of view and highlight some IMHB-associated misconceptions...
January 19, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30652331/rhodiola-species-a-comprehensive-review-of-traditional-use-phytochemistry-pharmacology-toxicity-and-clinical-study
#7
REVIEW
Hongxun Tao, Xu Wu, Jiliang Cao, Yu Peng, Anqi Wang, Jin Pei, Jianbo Xiao, Shengpeng Wang, Yitao Wang
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. We first outline both traditional and current use of Rhodiola for the treatment of various diseases. A detailed summary and comparison of chemical, pharmacological, toxicological, and clinical studies of various Rhodiola species highlight recent scientific advances and gaps, which gives insights into the understanding of Rhodiola application and would be helpful to improve the situation of biological resources and diversities of Rhodiola plants...
January 16, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30648267/antiaging-effects-of-bioactive-molecules-isolated-from-plants-and-fungi
#8
REVIEW
Jan Martel, David M Ojcius, Yun-Fei Ko, Chih-Jung Chang, John D Young
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. Many compounds isolated from plants and fungi prolong lifespan and prevent age-related diseases in model organisms...
January 15, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30628099/multidisciplinary-approaches-for-targeting-the-secretase-protein-family-as-a-therapeutic-route-for-alzheimer-s-disease
#9
REVIEW
Nalini Schaduangrat, Veda Prachayasittikul, Saowapak Choomwattana, Prapimpun Wongchitrat, Kamonrat Phopin, Wilasinee Suwanjang, Aijaz Ahmad Malik, Bruno Vincent, Chanin Nantasenamat
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. Efforts aimed at identifying AD drugs have mostly focused on the development of disease-modifying agents in which effects are believed to be long lasting...
January 9, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30604512/monoamine-oxidase-b-inhibitors-as-potential-neurotherapeutic-agents-an-overview-and-update
#10
REVIEW
Rati Kailash Prasad Tripathi, Senthil Raja Ayyannan
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. This review summarizes our current understanding on MAO-A/MAO-B including their structure, catalytic mechanism, and biological functions with emphases on the role of MAO-B as a potential therapeutic target for the development of medications treating neurodegenerative disorders...
January 2, 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30584800/norovirus-antivirals-where-are-we-now
#11
REVIEW
Natalie E Netzler, Daniel Enosi Tuipulotu, Peter A White
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...
December 25, 2018: Medicinal Research Reviews
https://read.qxmd.com/read/30569509/a-magic-drug-target-androgen-receptor
#12
REVIEW
Dan Li, Wenfang Zhou, Jinping Pang, Qin Tang, Bingling Zhong, Chao Shen, Li Xiao, Tingjun Hou
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...
December 19, 2018: Medicinal Research Reviews
https://read.qxmd.com/read/30548868/harnessing-the-untapped-potential-of-nucleotide-binding-oligomerization-domain-ligands-for-cancer-immunotherapy
#13
REVIEW
Sanja Nabergoj, Irena Mlinarič-Raščan, Žiga Jakopin
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...
December 13, 2018: Medicinal Research Reviews
https://read.qxmd.com/read/30506705/evolution-of-efficacious-pangenotypic-hepatitis-c-virus-therapies
#14
REVIEW
Muhammad Usman Ashraf, Kanzal Iman, Muhammad Farhan Khalid, Hafiz Muhammad Salman, Talha Shafi, Momal Rafi, Nida Javaid, Rashid Hussain, Fayyaz Ahmad, Syed Shahzad-Ul-Hussan, Shaper Mirza, Muhammad Shafiq, Samia Afzal, Sadia Hamera, Saima Anwar, Romena Qazi, Muhammad Idrees, Sohail A Qureshi, Safee Ullah Chaudhary
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. Subsequently, establishment of cell-based replicon systems enabled investigations into various stages of HCV life cycle including its entry, replication, translation, and assembly, as well as role of host proteins...
December 2, 2018: Medicinal Research Reviews
https://read.qxmd.com/read/30484872/design-of-hedgehog-pathway-inhibitors-for-cancer-treatment
#15
REVIEW
Jitender Bariwal, Virender Kumar, Yuxiang Dong, Ram I Mahato
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. While the majority of Hh pathway inhibitors target the transmembrane protein Smoothened (SMO), some small molecules that target the signaling cascade downstream of SMO are of particular interest...
November 28, 2018: Medicinal Research Reviews
https://read.qxmd.com/read/30565725/molecules-targeting-the-androgen-receptor-ar-signaling-axis-beyond-the-ar-ligand-binding-domain
#16
REVIEW
N G R Dayan Elshan, Matthew B Rettig, Michael E Jung
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. All clinically approved drugs for PCa ultimately target the AR-LBD...
November 22, 2018: Medicinal Research Reviews
https://read.qxmd.com/read/30462853/development-and-therapeutic-potential-of-autotaxin-small-molecule-inhibitors-from-bench-to-advanced-clinical-trials
#17
REVIEW
Alexios N Matralis, Antreas Afantitis, Vassilis Aidinis
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...
November 21, 2018: Medicinal Research Reviews
https://read.qxmd.com/read/29846945/progress-and-challenges-in-the-prevention-and-control-of-nonalcoholic-fatty-liver-disease
#18
REVIEW
Jingjing Cai, Xiao-Jing Zhang, Hongliang Li
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier...
January 2019: Medicinal Research Reviews
https://read.qxmd.com/read/30456874/topoisomerase-1b-poisons-over-a-half-century-of-drug-leads-clinical-candidates-and-serendipitous-discoveries
#19
REVIEW
Maris A Cinelli
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. In this review, agents that poison Top1 (and have thus been investigated for their anticancer properties) are surveyed, including natural products (such as camptothecins and indolocarbazoles), semisynthetic camptothecin and luotonin derivatives, and synthetic compounds (such as benzonaphthyridines, aromathecins, and indenoisoquinolines), as well as targeted therapies and conjugates...
November 19, 2018: Medicinal Research Reviews
https://read.qxmd.com/read/30450666/recent-clinical-trends-in-toll-like-receptor-targeting-therapeutics
#20
REVIEW
Muhammad Ayaz Anwar, Masaud Shah, Jason Kim, Sangdun Choi
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. Ligands reported as stand-alone drugs may also be reported based on their use in combinatorial therapeutics as adjuvants...
November 18, 2018: Medicinal Research Reviews
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