27,083 results match your criteria Biochemical Pharmacology[Journal]


Preclinical studies of a novel snake venom-derived recombinant disintegrin with antitumor activity: A review.

Biochem Pharmacol 2020 Jul 11:114149. Epub 2020 Jul 11.

Department of Biochemistry and Molecular Medicine, KSOM, USC, Los Angeles, CA 90089, USA. Electronic address:

Snake venoms consist of a complex mixture of many bioactive molecules. Among them are disintegrins, which are peptides without enzymatic activity, but with high binding affinity for integrins, transmembrane receptors that function to connect cells with components of the extracellular matrix. Integrin-mediated cell attachment is critical for cell migration and dissemination, as well as for signal transduction pathways involved in cell growth. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114149DOI Listing

Recombinant production, bioconjugation and membrane binding studies ofPn3a, a selective Na1.7 inhibitor.

Biochem Pharmacol 2020 Jul 11:114148. Epub 2020 Jul 11.

Centre for Advanced Imaging The University of Queensland. Electronic address:

Chronic pain is a common and often debilitating condition. Existing treatments are either inefficacious or associated with a wide range of side effects. The progress on developing safer and more effective analgesics has been slow, in large part due to our limited understanding of the physiological mechanisms underlying pain in different diseases. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114148DOI Listing

20(S)-ginsenoside Rg3 promotes myoblast differentiation and protects against myotube atrophy via regulation of the Akt/mTOR/FoxO3 pathway.

Biochem Pharmacol 2020 Jul 9:114145. Epub 2020 Jul 9.

Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, 1478 Gongnong Street, Changchun, Jilin Province, 130021, PR China; Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education. Electronic address:

We previously found that 20(S)-ginsenoside Rg3 (S-Rg3) promotes myoblast differentiation via an unknown mechanism. Here we measured levels of myosin heavy chain (MHC) and myogenin, markers of myoblast differentiation, using Western blot analysis and immunofluorescence staining. Notably, S-Rg3 treatment of C2C12 myoblasts led to increased muscle differentiation and protection from muscle atrophy in a dexamethasone (DEX)-treated C2C12 myotube-based muscle atrophy model. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114145DOI Listing

The PAR4-derived pepducin P4Pal lacks effect on neutrophil GPCRs that couple to Gαq for signaling but distinctly modulates function of the Gαi-coupled coupled FPR2 and FFAR2.

Biochem Pharmacol 2020 Jul 9:114143. Epub 2020 Jul 9.

Department of Rheumatology and Inflammation Research, Institute of Medicine at the Sahlgrenska academy, University of Gothenburg, Gothenburg, Sweden.

A novel mechanism of action was described for the protease-activated receptor 4 (PAR4)-derived pepducin (P4Pal), when it was shown to exhibit inhibitory efficacy towards G protein coupling to multiple Gαq-coupled receptors (Carr R 3rd et al, Mol Pharmacol. 2016;89:94). We could confirm that P4Pal, similar to an earlier-characterized Gαq inhibitor (YM-254890), inhibited platelet aggregation induced by agonists for the Gαq-coupled receptors PAR1 and PAR4. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114143DOI Listing

Type 2 diabetes mellitus decreases systemic exposure of clopidogrel active metabolite through upregulation of P-glycoprotein in rats.

Biochem Pharmacol 2020 Jul 9:114142. Epub 2020 Jul 9.

School of Life Sciences, Jilin University, Changchun, China. Electronic address:

Patients with diabetic mellitus tend to have a poor response to clopidogrel (Clop) due to reduced generation of active metabolite (Clop-AM). However, the underlying mechanism is not elucidated. A type 2 diabetic mellitus (T2DM) rat model was established by combining high-fat diet feeding and low-dose streptozotocin (STZ) injection. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114142DOI Listing

Design and Pharmacological Profile of a Novel Covalent Partial Agonist for the Adenosine A Receptor.

Biochem Pharmacol 2020 Jul 9:114144. Epub 2020 Jul 9.

Division of Drug Discovery and Safety, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 9502, 2300RA Leiden, The Netherlands. Electronic address:

Partial agonists for G protein-coupled receptors (GPCRs) provide opportunities for novel pharmacotherapies with enhanced on-target safety compared to full agonists. For the human adenosine A receptor (hAAR) this has led to the discovery of capadenoson, which has been in phase IIa clinical trials for heart failure. Accordingly, the design and profiling of novel hAAR partial agonists has become an important research focus. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114144DOI Listing

Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective.

Biochem Pharmacol 2020 Jul 9:114147. Epub 2020 Jul 9.

Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, West Bengal, India; Division of Molecular Medicine, Bose Institute, P-1/12, CIT Rd, Scheme VIIM, Kankurgachi, Kolkata, West Bengal 700054 India. Electronic address:

Owing to the efficacy in reducing pain and inflammation non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most popularly used medicines, confirming their position in the WHO's Model List of Essential Medicines. With escalating musculoskeletal complications, as evident from 2016 Global Burden of Disease data, NSAID usage is evidently unavoidable. Apart from analgesic, anti-inflammatory and antipyretic efficacies, NSAIDs are further documented to offer protection against diverse critical disorders including cancer and heart attacks. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7347500PMC

The voltage-gated potassium channel K1.3 as a therapeutic target for venom-derived peptides.

Biochem Pharmacol 2020 Jul 9:114146. Epub 2020 Jul 9.

Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia; ARC Centre for Fragment-Based Design, Monash University, Parkville, Victoria 3052, Australia. Electronic address:

The voltage-gated potassium channel K1.3 is a well-established therapeutic target for a range of autoimmune diseases, in addition to being the site of action of many venom-derived peptides. Numerous studies have documented the efficacy of venom peptides that target K1. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114146DOI Listing

Corrigendum to "'Heme oxygenase-1 induction by methylene blue protects RAW264.7 cells from hydrogen peroxide-induced injury" [Biochem Pharmacol 148 (2018) 265-277].

Biochem Pharmacol 2020 Jul 8;180:114131. Epub 2020 Jul 8.

Department of Anesthesiology, the Wuxi People Hospital, 200 Qingyang Road, Wuxi 214023, China. Electronic address:

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http://dx.doi.org/10.1016/j.bcp.2020.114131DOI Listing

Human Red Blood Cell Uptake and Sequestration of Arsenite and Selenite: Evidence of Seleno-bis(S-glutathionyl) Arsinium Ion Formation in Human Cells.

Biochem Pharmacol 2020 Jul 8:114141. Epub 2020 Jul 8.

Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Canada; Membrane Protein Disease Research Group, University of Alberta, Canada; Department of Physiology, University of Alberta, Canada. Electronic address:

Over 200 million people worldwide are exposed to the human carcinogen, arsenic, in contaminated drinking water. In laboratory animals, arsenic and the essential trace element, selenium, can undergo mutual detoxification through the formation of the seleno-bis(S-glutathionyl) arsinium ion [(GS)AsSe], which undergoes biliary and fecal elimination. [(GS)AsSe], formed in animal red blood cells (RBCs), sequesters arsenic and selenium, and slows the distribution of both compounds to peripheral tissues susceptible to toxic effects. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114141DOI Listing

Galantamine improves enhanced impulsivity, impairments of attention and long-term potentiation induced by prenatal nicotine exposure to mice.

Biochem Pharmacol 2020 Jul 8:114139. Epub 2020 Jul 8.

Advanced Diagnostic System Research Laboratory, Graduate School of Health Sciences, Fujita Health University, Toyoake, Japan; Japanese Drug Organization of Appropriate Use and Research, Nagoya, Japan.

Prenatal nicotine exposure (PNE) causes behavioral abnormalities in offspring, such as an enhancement of impulsivity and decrease in attention at adolescence. Here we examined the effects of galantamine (GAL) on the behavioral and electrophysiological changes induced by PNE in mice. Pregnant C57BL/6J mice were exposed to nicotine (0. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114139DOI Listing

Protective Effects of morin against depressive-like behavior prompted by chronic unpredictable mild stress in rats: Possible role of inflammasome-related pathways.

Biochem Pharmacol 2020 Jul 8:114140. Epub 2020 Jul 8.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

Depression is a common mental illness that possesses a noteworthy effect on patients' lives. Many theories are recently studied for their plausible involvement in depression pathogenesis, especially oxidative stress and inflammation. Morin (2',3,4',5,7-pentahydroxyflavone), a natural flavonoid, is characterized by its potent anti-inflammatory, and anti-oxidant activities. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114140DOI Listing

Potential roles of PP2A-Rac1 signaling axis in pancreatic β-cell dysfunction under metabolic stress: Progress and Promise.

Biochem Pharmacol 2020 Jul 4:114138. Epub 2020 Jul 4.

Biomedical Laboratory Research Service, John D. Dingell VA Medical Center and Departments of Pharmaceutical Sciences and Internal Medicine, Wayne State University, Detroit, MI 48201, United States. Electronic address:

Recent estimates by the International Diabetes Federation suggest that the incidence of diabetes soared to an all-time high of 463 million in 2019, and the federation predicts that by 2045 the number of individuals afflicted with this disease will increase to 700 million. Therefore, efforts to understand the pathophysiology of diabetes are critical for moving toward the development of novel therapeutic strategies for this disease. Several contributors (oxidative stress, endoplasmic reticulum stress and others) have been proposed for the onset of metabolic dysfunction and demise of the islet β-cell leading to the pathogenesis of diabetes. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114138DOI Listing

Overexpression of ABCB1 and ABCG2 contributes to reduced efficacy of the PI3K/mTOR inhibitor samotolisib (LY3023414) in cancer cell lines.

Biochem Pharmacol 2020 Jul 4:114137. Epub 2020 Jul 4.

Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, United States.

LY3023414 (samotolisib) is a promising new dual inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR). Currently, multiple clinical trials are underway to evaluate the efficacy of LY3023414 in patients with various types of cancer. However, the potential mechanisms underlying acquired resistance to LY3023414 in human cancer cells still remain elusive. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114137DOI Listing

Oridonin is an antidepressant molecule working through the PPAR-γ/AMPA receptor signaling pathway.

Authors:
Ping Liu Jing Du

Biochem Pharmacol 2020 Jul 3;180:114136. Epub 2020 Jul 3.

School of Medicine, Yunnan University, Kunming, Yunnan, PR China. Electronic address:

Oridonin is a diterpene compound that regulates the activity of PPAR-γ (peroxisome proliferator-activated receptor gamma) transcription factor. Cumulative evidence indicates that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors (AMPARs) play an important role in the treatment of depression. In the article, we found that after treatment with oridonin, the immobility time of mice was significantly reduced in the tail suspension test (TST) and the forced-swim test (FST). Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114136DOI Listing

β-estradiol adjusts intestinal function via ERβ and GPR30 mediated PI3K/AKT signaling activation to alleviate postmenopausal dyslipidemia.

Biochem Pharmacol 2020 Jul 3;180:114134. Epub 2020 Jul 3.

School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Decreases in estrogen secretion and estrogen receptor function lead to an increase in the incidence of dyslipidemia and cardiovascular disease (CVD) in postmenopausal women. We previously reported that β-estradiol has a significant regulatory effect on lipids in ApoE mice with bilateral ovariectomy. In the present study, we investigated how β-estradiol regulates intestinal function via estrogen receptors to alleviate postmenopausal dyslipidemia. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114134DOI Listing
July 2020
5.009 Impact Factor

Snake Antivenom: challenges and alternate approaches.

Biochem Pharmacol 2020 Jul 3:114135. Epub 2020 Jul 3.

School of Biotechnology, Amrita Vishwa Vidyapeetham, Clappana P.O, Kollam, Kerala, 690 525, India. Electronic address:

Snake envenomation is still a serious threat to many countries in the world. The only mainstay treatment depends on the administration of animal derived immunoglobulin based antivenom. Significant limitations to these antivenoms are a challenge in the treatment of snake envenomation. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114135DOI Listing

Characterization of the mechanism of action of RDR01752, a novel corrector of F508del-CFTR.

Biochem Pharmacol 2020 Jul 3;180:114133. Epub 2020 Jul 3.

University of Lisboa, Faculty of Sciences, BioISI Biosystems & Integrative Sciences Institute, Lisboa, Portugal. Electronic address:

Despite progress in developing pharmacotherapies to rescue F508del-CFTR, the most prevalent Cystic Fibrosis (CF)-causing mutation, individuals homozygous for this mutation still face several disease-related symptoms. Thus, more potent compound combinations are still needed. Here, we investigated the mechanism of action (MoA) of RDR01752, a novel F508del-CFTR trafficking corrector. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114133DOI Listing
July 2020
5.009 Impact Factor

Rutaecarpine derivative Cpd-6c alleviates acute kidney injury by targeting PDE4B, a key enzyme mediating inflammation in cisplatin nephropathy.

Biochem Pharmacol 2020 Jul 3;180:114132. Epub 2020 Jul 3.

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, The Key Laboratory of Anti-inflammatory of Immune Medicines, Ministry of Education, Hefei 230032, China. Electronic address:

Acute kidney injury (AKI), characterized by a rapid decline in renal function, is triggered by an acute inflammatory response that leads to kidney damage. An effective treatment for AKI is lacking. Using in vitro and in vivo AKI models, our laboratory has identified a series of anti-inflammatory molecules and their derivatives. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114132DOI Listing
July 2020
5.009 Impact Factor

Evolution of a concept: From accessory protein to key virulence factor, the case of HIV-1 Vpr.

Biochem Pharmacol 2020 Jun 30;180:114128. Epub 2020 Jun 30.

University of Strasbourg, Research Unit7292, DHPI, IUT Louis Pasteur, Schiltigheim, France. Electronic address:

Back in 1989 some studies have shown that the viral protein Vpr was dispensable for HIV-1 replication in vitro. From then the concept of accessory or auxiliary protein for Vpr has emerged and it is still used to date. However, Vpr soon appeared to be very important for in vivo virus spread and pathogenesis. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114128DOI Listing

Neuropeptide signalling systems -an underexplored target for venom drug discovery.

Biochem Pharmacol 2020 Jun 30:114129. Epub 2020 Jun 30.

Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia; University of Vienna, Faculty of Chemistry, Institute of Biological Chemistry, Vienna, Austria. Electronic address:

Neuropeptides are signalling molecules mainly secreted from neurons that act as neurotransmitters or peptide hormones to affect physiological processes and modulate behaviours. In humans, neuropeptides are implicated in numerous diseases and understanding their role in physiological processes and pathologies is important for therapeutic development. Teasing apart the (patho)physiology of neuropeptides remains difficult due to ligand and receptor promiscuity and the complexity of the signalling pathways. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114129DOI Listing

GR-C/EBPα-IGF1 axis mediated azithromycin-induced liver developmental toxicity in fetal mice.

Biochem Pharmacol 2020 Jun 29;180:114130. Epub 2020 Jun 29.

Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic address:

Azithromycin is considered an effective drug to treat the perinatal mycoplasma infection. However, there is a lack of studies on developmental toxicity of azithromycin. In this study, we observed the developmental toxicity of fetal liver induced by prenatal azithromycin exposure (PAE) in mice and explored the potential mechanism. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114130DOI Listing
June 2020
5.009 Impact Factor

Pharmacokinetics of Gemcitabine and its Amino Acid Ester Prodrug following Intravenous and Oral Administrations in Mice.

Biochem Pharmacol 2020 Jun 27:114127. Epub 2020 Jun 27.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Gemcitabine is an intravenously administered anti-cancer nucleoside analogue. Systemic exposure following oral administration of gemcitabine is limited by extensive first-pass metabolism via cytidine deaminase (CDA) and potentially by saturation of nucleoside transporter-mediated intestinal uptake. An amino acid ester prodrug of gemcitabine, 5'-l-valyl-gemcitabine (V-Gem), was previously shown to be a substrate of the intestinally expressed peptide transporter 1 (PEPT1) and stable against CDA-mediated metabolism. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114127DOI Listing

Macrophages confer resistance to BET inhibition in triple-negative breast cancer by upregulating IKBKE.

Biochem Pharmacol 2020 Jun 27;180:114126. Epub 2020 Jun 27.

MOE Key Laboratory of Laser Life Science, Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address:

BET inhibitors (BETi) exhibit a strong anti-tumor activity in triple-negative breast cancer (TNBC). However, BETi resistance has been reported in TNBC. The mechanisms of resistance have not been demonstrated. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114126DOI Listing

The management of severe asthma in 2020.

Biochem Pharmacol 2020 Jun 27:114112. Epub 2020 Jun 27.

Quebec Heart and Lung Institute, Laval University, Canada. Electronic address:

Asthma is a chronic inflammatory disease of the airways affecting more than 300 million patients worldwide. The disease can be of various severity ranging from very mild to severe. The severe form of the disease only affects about 5% of patients but is responsible for a large component of the overall disease burden and results in about half of direct asthma-related costs. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114112DOI Listing

The development of a targeted and more potent, anti-Inflammatory derivative of colchicine: Implications for gout.

Biochem Pharmacol 2020 Jun 26;180:114125. Epub 2020 Jun 26.

CHU de Québec Research Center-Université Laval, 2705 boulevard Laurier, Bloc T1-49, Québec, PQ, G1V 4G2, Canada; Department of Microbiology-Infectious Diseases and Immunology, Université Laval, Pavillon Ferdinand-Vandry, 1050 avenue de la Médecine, Université Laval, Québec G1V 0A6, PQ, Canada. Electronic address:

Background: Colchicine is routinely used for its anti-inflammatory properties to treat gout and Familial Mediterranean fever. More recently, it was also shown to be of therapeutic benefit for another group of diseases in which inflammation is a key component, namely, cardiovascular disease. Whilst there is considerable interest in repurposing this alkaloid, it has a narrow therapeutic index and is associated with undesirable side effects and drug interactions. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114125DOI Listing

Testing of natural products in clinical trials targeting the SARS-CoV-2 (Covid-19) viral spike protein-angiotensin converting enzyme-2 (ACE2) interaction.

Biochem Pharmacol 2020 Jun 25;178:114123. Epub 2020 Jun 25.

Department of Nutrition, Dietetics and Food, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, BASE Facility, 264 Ferntree Gully Road, Notting Hill, VIC 3168, Australia.

Commonly used drugs for treating many conditions are either natural products or derivatives. In silico modelling has identified several natural products including quercetin as potential highly effective disruptors of the initial infection process involving binding to the interface between the SARS-CoV-2 (Covid-19) Viral Spike Protein and the epithelial cell Angiotensin Converting Enzyme-2 (ACE2) protein. Here we argue that the oral route of administration of quercetin is unlikely to be effective in clinical trials owing to biotransformation during digestion, absorption and metabolism, but suggest that agents could be administered directly by alternative routes such as a nasal or throat spray. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316054PMC

Critical residue properties for potency and selectivity of α-Conotoxin RgIA towards α9α10 nicotinic acetylcholine receptors.

Biochem Pharmacol 2020 Jun 25:114124. Epub 2020 Jun 25.

School of Biological Sciences, University of Utah, Salt Lake City, UT 84112, USA; George E. Whalen Veterans Affairs Medical Center, Salt Lake City, UT 84112, USA; Department of Psychiatry, University of Utah, Salt Lake City, UT 84112, USA.

The α9α10 nicotinic acetylcholine receptor (nAChR) has been characterized as an effective anti-pain target that functions through a non-opioid mechanism. However, as a pentameric ion channel comprised of two different subunits, the specific targeting of α9α10 nAChRs has proven challenging. Previously the 13-amino-acid peptide, RgIA, was shown to block α9α10 nAChRs with high potency and specificity. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114124DOI Listing

TNF-α inhibition decreases MMP-2 activity, reactive oxygen species formation and improves hypertensive vascular hypertrophy independent of its effects on blood pressure.

Biochem Pharmacol 2020 Jun 25;180:114121. Epub 2020 Jun 25.

Unit of Biotechnology, University of Ribeirao Preto, UNAERP, Brazil. Electronic address:

Systemic arterial hypertension is a public health problem associated with an increased risk of cardiovascular disease. Matrix metalloproteinases (MMP) are endopeptidases that participate in hypertension-induced cardiovascular remodeling, which may be activated by oxidative stress. Angiotensin II (Ang II), a potent hypertrophic and vasoconstrictor peptide, increases oxidative stress, MMP-2 activity and tumor necrosis factor (TNF-α) expression. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114121DOI Listing

Natural cardenolides suppress coronaviral replication by downregulating JAK1 via a Na/K-ATPase independent proteolysise.

Biochem Pharmacol 2020 Jun 25;180:114122. Epub 2020 Jun 25.

Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli 35053, Taiwan, ROC. Electronic address:

An unprecedented biological function of natural cardenolides independent of their membrane target Na/K-ATPase is disclosed. Previously, we reported that cardenolides impart anti-transmissible gastroenteritis coronavirus (anti-TGEV) activity through the targeting of Na/K-ATPase and its associated PI3K_PDK1_RSK2 signaling. Swine testis cells with Na/K-ATPase α1 knocked down exhibited decreased susceptibility to TGEV infectivity and attenuated PI3K_PDK1_RSK2 signaling. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314687PMC

Neuropolybin: A new antiseizure peptide obtained from wasp venom.

Biochem Pharmacol 2020 Jun 23:114119. Epub 2020 Jun 23.

Neuropharmacology Laboratory, Institute of Biological Sciences, Department of Physiological Sciences, University of Brasília, Distrito Federal, DF, Brazil. Electronic address:

Epilepsy accounts for one of the most serious neurological disorders, and its treatment remains a challenge, due to high cost and harmful side effects. Bioactive molecules extracted from arthropod venoms are considered a promising therapy since these compounds are known for their highly selective and potent profiles. The purpose of this study was to identify and characterize the potential antiseizure effect of the peptide Ppnp7, extracted from the venom of the social wasp Polybia paulista, and also the effect of the bioinspired peptide, named Neuropolybin, in the same parameters. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114119DOI Listing

Perinatal exposure to nonylphenol delayed myelination in offspring cerebellum.

Biochem Pharmacol 2020 Jun 24;178:114120. Epub 2020 Jun 24.

Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China. Electronic address:

As a stable environmental contaminant, nonylphenol (NP) has been shown to induce some neurological deficits in the cerebellum, although the underlying mechanism is still unknown. In the present study, we aimed to investigate the effects of perinatal exposure to NP on myelination, an important process essential for the intact cerebellar function, in the offspring cerebellum. Exposure to NP delayed the myelination in the offspring cerebellum during perinatal period. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114120DOI Listing

RGFP966, a Histone deacetylase 3 inhibitor, promotes glioma stem cell differentiation by blocking TGF-β signaling via SMAD7.

Biochem Pharmacol 2020 Jun 22:114118. Epub 2020 Jun 22.

Key Laboratory of Pathobiology, Ministry of Education, and Department of pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, P.R. China. Electronic address:

Glioma stem cells (GSC) play a major role in drug resistance and tumor recurrence. Using a genetic screen with a set of shRNAs that can target chromatin regulators in a GSC model, we have HDAC3 as a major negative regulator of GSC differentiation. Inhibition of HDAC3 using a pharmacological inhibitor or a siRNA led to the induction of GSC differentiation into astrocytes. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114118DOI Listing
June 2020
5.009 Impact Factor

Downregulation of OCTN2 by cytokines plays an important role in the progression of inflammatory bowel disease.

Biochem Pharmacol 2020 Jun 21;178:114115. Epub 2020 Jun 21.

Laboratory of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Electronic address:

Inflammatory bowel diseases (IBD) are characterized by chronic relapsing disorders of the gastrointestinal tract. OCTN2 (SLC22A5) and its substrate l-carnitine (l-Car) play crucial roles in maintaining normal intestinal function. An aim of this study was to delineate the expression alteration of OCTN2 in IBD and its underlying mechanism. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114115DOI Listing
June 2020
5.009 Impact Factor

Identification of N-acyl amino acids that are positive allosteric modulators of glycine receptors.

Biochem Pharmacol 2020 Jun 21;180:114117. Epub 2020 Jun 21.

Discipline of Pharmacology, School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia. Electronic address:

Glycine receptors (GlyRs) mediate inhibitory neurotransmission within the spinal cord and play a crucial role in nociceptive signalling. This makes them primary targets for the development of novel chronic pain therapies. Endogenous lipids have previously been shown to modulate glycine receptors and produce analgesia in pain models, however little is known about what chemical features mediate these effects. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114117DOI Listing

Inhibition of RUNX1 Promotes Cisplatin-induced Apoptosis in Ovarian Cancer Cells.

Biochem Pharmacol 2020 Jun 21:114116. Epub 2020 Jun 21.

Department of Biological Sciences & Technology, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address:

Runt-related transcription factor 1 (RUNX1), one subunit of core-binding factors in hematopoiesis and leukemia, was highly expressed in ovarian cancer (OC), but the role of RUNX1 in OC is largely unknown. Since we found that high expression of RUNX1 is correlated with poor survival in patients with OC through bioinformatic analysis of TCGA database, we developed RUNX1-knockout clones by CRISPR/Cas9 technique and discovered that RUNX1 depletion could promote cisplatin-induced apoptosis in OC cells, which was further confirmed by RUNX1 knockdown and overexpression. We also proved that RUNX1 could elevate the expression of BCL2. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114116DOI Listing

Snake venom three-finger toxins and their potential in drug development targeting cardiovascular diseases.

Biochem Pharmacol 2020 Jun 21:114105. Epub 2020 Jun 21.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore. Electronic address:

Cardiovascular diseases such as coronary and peripheral artery diseases, venous thrombosis, stroke, hypertension, and heart failure are enormous burden to health and economy globally. Snake venoms have been the sources of discovery of successful therapeutics targeting cardiovascular diseases. For example, the first-in-class angiotensin-converting enzyme inhibitor captopril was designed largely based on bradykinin-potentiating peptides from Bothrops jararaca venom. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114105DOI Listing

Multi-targeting sodium and calcium channels using venom peptides for the treatment of complex ion channels-related diseases.

Biochem Pharmacol 2020 Jun 21:114107. Epub 2020 Jun 21.

Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Rd., St Lucia, QLD AU 4072, Australia.

Venom peptides are amongst the most exquisite group of bioactive molecules able to alter the normal physiology of organisms. These bioactive peptides penetrate tissues and blood vessels to encounter a number of receptors and ion channels to which they bind with high affinity and execute modulatory activities. Arachnid is the most diverse class of venomous animals often rich in peptides modulating voltage-gated sodium (Na), calcium (Ca), and potassium (K) channels. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114107DOI Listing

SARS-CoV-2 and cardiovascular complications: From molecular mechanisms to pharmaceutical management.

Biochem Pharmacol 2020 Jun 21;178:114114. Epub 2020 Jun 21.

Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai 200032, China; School of Pharmacy, University of Wyoming College of Health Sciences, Laramie, WY 82071 USA; Department of Pathology, University of Washington Seattle, Seattle, WA, USA. Electronic address:

The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306106PMC

Galectin-3 expression and secretion by tumor-associated macrophages in hypoxia promotes breast cancer progression.

Biochem Pharmacol 2020 Jun 21;178:114113. Epub 2020 Jun 21.

Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China. Electronic address:

Tumor-associated macrophages (TAMs) have been shown to be associated with poor prognosis of cancer and are predominately localized in the hypoxia regions of tumor. We demonstrated in this study that hypoxia increases the synthesis and secretion of galectin-3 by TAMs. The increased expression of galectin-3 in TAMs was seen to be associated with nucleation of transcription factor NF-κB through generation and activation of ROS and promoted tumor growth and metastasis in vitro and in mice through multiple molecular mechanisms. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114113DOI Listing

Effects of protein-protein interface disruptors at the ligand of the glucocorticoid-induced tumor necrosis factor receptor-related gene (GITR).

Biochem Pharmacol 2020 Jun 20;178:114110. Epub 2020 Jun 20.

Department of Biomedical and Biotechnological Sciences University of Catania, Catania, Italy.

The tumor necrosis factor (TNF) superfamily (TNFSF) includes about thirty structurally related receptors (TNFSFRs) and about twenty protein ligands that bind to one or more of these receptors. Receptors of the tumor necrosis factor (TNF) superfamily (TNFSFRs) are pharmacological targets for treatment of inflammatory and autoimmune diseases. Currently, drugs targeting TNFSFR signaling are biological drugs (monoclonal antibodies, decoy receptors) aimed at binding and sequestering TNFSFR ligands. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114110DOI Listing

Interpersonal brain synchronization with instructor compensates for learner's sleep deprivation in interactive learning.

Biochem Pharmacol 2020 Jun 20:114111. Epub 2020 Jun 20.

Neuropsychology and Functional Neuroimaging Research Unit (UR2NF) at CRCN - Center for Research in Cognition and Neurosciences and UNI - ULB Neurosciences Institute, Université Libre de Bruxelles, Bruxelles, Belgium. Electronic address:

Recent advances shifted the focus on single-brain functioning toward two-brain communication during learning interactions, following the demonstration that interpersonal brain synchronization (IBS) can track instructor-learner information exchange. Here, we investigated (i) whether sleep deprivation (SD) that potentially impacts both social interactions and learning abilities modulates IBS, and (ii) conversely whether and to what extent IBS might compensate for SD-related learning deficits. Instructors (always with regular sleep, RS) were asked to teach numerical reasoning strategies to learners (either SD or RS), during which the activity of both brains was simultaneously recorded using functional near-infrared spectroscopy (fNIRS). Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114111DOI Listing

A combination of inhibiting microglia activity and remodeling gut microenvironment suppresses the development and progression of experimental autoimmune uveitis.

Biochem Pharmacol 2020 Jun 19:114108. Epub 2020 Jun 19.

School of Ophthalmology & Optometry and Eye Hospital, Institute of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China; State Key Laboratory of Optometry & Vision Science, Wenzhou 325027, Zhejiang, China. Electronic address:

Noninfectious (autoimmune and immune-mediated) uveitis is an ocular inflammatory disease which can lead to blindness in severe cases. Due to the potential side effects of first-line drugs for clinical uveitis, novel drugs and targets against uveitis are still urgently needed. In the present study, using rat experimental autoimmune uveitis (EAU) model, we first found that minocycline treatment can substantially inhibit the development of EAU and improve the retinal function by suppressing the retinal microglial activation, and block the infiltration of inflammatory cells, including Th17, into the retina by decreasing the major histocompatibility complex class II (MHC II) expression in resident and infiltrating cells. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114108DOI Listing

Gestational dioxin exposure suppresses prolactin-stimulated nursing in lactating dam rats to impair development of postnatal offspring.

Biochem Pharmacol 2020 Jun 20;178:114106. Epub 2020 Jun 20.

Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:

A number of epidemiological studies have implicated environmental chemicals including dioxins in the induction of negative effects on child development. To clarify the underlying mechanisms, almost all toxicologists have concentrated on effects on the offspring themselves. We examined an alternative hypothesis that gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly-toxic dioxin, targets factors related to maternal childcare to disturb offspring development. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114106DOI Listing

Analysis of polyphenolic metabolites from in vitro gastrointestinal digested soft fruit extracts identify malvidin-3-glucoside as an inhibitor of PTP1B.

Biochem Pharmacol 2020 Jun 20;178:114109. Epub 2020 Jun 20.

The Rowett Institute, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.

Protein-tyrosine phosphatase 1B (PTP1B, EC 3.1.3. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114109DOI Listing

Celastrol ameliorates autoimmune disorders in Trex1-deficient mice.

Biochem Pharmacol 2020 Jun 19;178:114090. Epub 2020 Jun 19.

Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, China; College of Life Science, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University Qishan Campus, No.1 Keji Road, University City, Fuzhou, Fujian 350117, China. Electronic address:

Celastrol is one of most potent bioactive molecule isolated from the medicinal plant Tripterygium wilfordii (Thunder God Vine) and is well known for its potential therapeutic value against various chronic diseases including the autoimmune diseases, such as systemic lupus erythematosus and Aicardi-Goutieres syndrome, or other interferonopathies. However, the underlying mechanism of celastrol function remains unclear. Here we showed that celastrol caused inhibition of interferon regulatory factor 3 (IRF3) activation leading to the down-regulation of the interferon response triggered by cytosolic nucleic acids in vitro and in vivo. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114090DOI Listing
June 2020
5.009 Impact Factor

Combined anti-fibrotic and anti-inflammatory properties of JAK-inhibitors on macrophages in vitro and in vivo: Perspectives for scleroderma-associated interstitial lung disease.

Biochem Pharmacol 2020 Jun 17;178:114103. Epub 2020 Jun 17.

Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, F-35000 Rennes, France. Electronic address:

Janus kinase (JAK) inhibitors (also termed Jakinibs) constitute a family of small drugs that target various isoforms of JAKs (JAK1, JAK2, JAK3 and/or tyrosine kinase 2 (Tyk2)). They exert anti-inflammatory properties linked, in part, to the modulation of the activation state of pro-inflammatory M1 macrophages. The exact impact of JAK inhibitors on a wider spectrum of activation states of macrophages is however still to be determined, especially in the context of disorders involving concomitant activation of pro-inflammatory M1 macrophages and profibrotic M2 macrophages. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114103DOI Listing
June 2020
5.009 Impact Factor

Ionizing radiation induces BH deficiency by downregulating GTP-cyclohydrolase 1, a novel target for preventing and treating radiation enteritis.

Biochem Pharmacol 2020 Jun 17;180:114102. Epub 2020 Jun 17.

Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi'an, PR China. Electronic address:

Radiation enteritis (RE) is a common side effect after radiotherapy for abdominal cancer. RE pathogenesis is complicated, with no drugs available for prevention or treatments. Intestinal ischemia is a key factor in the occurrence and development of enteritis. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114102DOI Listing

Targeting mitochondria in melanoma: Interplay between MAPK signaling pathway and mitochondrial dynamics.

Biochem Pharmacol 2020 Jun 17;178:114104. Epub 2020 Jun 17.

Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil. Electronic address:

Melanoma is a malignant proliferative disease originated in melanocytes, characterized by high metastatic activity and by the activation of oncogenes, such as B-RAF (40-60% of cases). Recent studies have shown that vemurafenib (a MAPK inhibitor) promoted disturbance of mitochondrial bioenergetics, although underlying mechanisms are not fully comprehended. Here we showed that MAPK inhibition by vemurafenib in B-RAF-mutated human melanoma culminated in the inhibition of DRP1 phosphorylation, associated to a large mitochondrial network remodeling to the hyperfused phenotype, and increased oxidative phosphorylation capacity. Read More

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http://dx.doi.org/10.1016/j.bcp.2020.114104DOI Listing

Exhaled nitric oxide and its predictive power related to lung function and bronchial inflammation.

Biochem Pharmacol 2020 Jun 14:114101. Epub 2020 Jun 14.

Chest Department, Erasme University Hospital, Université libre de Bruxelles, Brussels, Belgium.

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http://dx.doi.org/10.1016/j.bcp.2020.114101DOI Listing