keyword
MENU ▼
Read by QxMD icon Read
search

pde4 inhibitor

keyword
https://www.readbyqxmd.com/read/28638635/crystal-structure-of-an-apremilast-ethanol-hemisolvate-hemihydrate-solvatomorph
#1
Yun-Deng Wu, Xiao-Hong Liu, Jian Xu, Si-Han Zhang, Kun Shen, Ling Sun, Yong-Mei He, Yan Ma, Ai-Hua Zhang
The title compound, C22H24N2O7S·0.5C2H5OH·0.5H2O {systematic name: (S)-4-acetamido-2-[1-(3-eth-oxy-4-meth-oxy-phen-yl)-2-(methyl-sulfon-yl)eth-yl]iso-indo-line-1,3-dione ethanol hemisolvate hemihydrate}, is a novel solvatomorph of apremilast (AP), which is an inhibitor of phosphodiesterase 4 (PDE4) and is indicated for the treatment of adult patients with active psoriatic arthritis. The asymmetric unit contains one mol-ecule of AP and disordered mol-ecules of ethanol and water, both with half occupancy. The dihedral angle between the planes of the phenyl ring and the iso-indole ring is 67...
June 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28618988/synthesis-docking-and-anti-inflammatory-activity-of-triazole-amine-derivatives-as-potential-phosphodiesterase-4-inhibitors
#2
Ajmer Singh Grewal, Viney Lather, Deepti Pandita, Ruchi Dalal
BACKGROUND: Phosphodiesterase 4 (PDE4), one of the member of PDE superfamily catalyzes, the hydrolysis of cyclic adenosine monophosphate to adenosine monophosphate in pro-inflammatory and immunomodulatory cells leading to increased inflammatory processes. PDE4 has been reported as an attractive therapeutic target involved in various inflammatory disorders. OBJECTIVE: The present work was designed to synthesize and evaluate the anti-inflammatory activity of some new triazole amine derivatives as potential PDE4 inhibitors...
June 16, 2017: Anti-inflammatory & Anti-allergy Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28617319/pde4-inhibition-and-inflammatory-bowel-disease-a-novel-therapeutic-avenue
#3
REVIEW
Marco Spadaccini, Silvia D'Alessio, Laurent Peyrin-Biroulet, Silvio Danese
BACKGROUND: In the last few decades, a better knowledge of the inflammatory pathways involved in the pathogenesis of Inflammatory Bowel Disease (IBD) has promoted biological therapy as an important tool to treat IBD patients. However, in spite of a wider spectrum of biological drugs, a significant proportion of patients is unaffected by or lose their response to these compounds, along with increased risks of infections and malignancies. For these reasons there is an urgent need to look for new pharmacological targets...
June 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28613871/discovery-of-n-4-5-4-fluoro-phenyl-3-methyl-2-methylsulfanyl-3h-imidazol-4-yl-pyridin-2-yl-acetamide-cbs-3595-a-dual-p38%C3%AE-mapk-pde-4-inhibitor-with-activity-against-tnf%C3%AE-related-diseases
#4
Wolfgang Albrecht, Anke Unger, Silke M Bauer, Stefan A Laufer
The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4) and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha (TNFα) release...
June 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28605578/roflupram-a-phosphodiesterase-4-inhibitior-suppresses-inflammasome-activation-through-autophagy-in-microglial-cells
#5
Tingting You, Yu-Fang Cheng, Jiahong Zhong, Bingtian Bi, Bingqing Zeng, Wenhua Zheng, Hai-Tao Wang, Jiang-Ping Xu
Inhibition of phosphodiesterase 4 (PDE4) suppressed the inflammatory responses in the brain. However, the underlying mechanisms are poorly understood. Roflupram (ROF) is a novel PDE4 inhibitor. In the present study, we found that ROF enhanced the level of microtubule-associated protein 1 light chain 3 II (LC3-II) and decreased p62 in microglial BV-2 cells. Enhanced fluorescent signals were observed in BV-2 cells treated with ROF by Lysotracker red and acridine orange staining. In addition, immunofluorescence indicated a significant increase in punctate LC3...
June 12, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28603838/compartmentalized-camp-responses-to-prostaglandin-ep2-receptor-activation-in-human-airway-smooth-muscle-cells
#6
Shailesh R Agarwal, Kathryn Miyashiro, Htun Latt, Rennolds S Ostrom, Robert D Harvey
BACKGROUND AND PURPOSE: Previous studies indicate that prostaglandin EP2 receptors (EP2 Rs) selectively couple to adenylyl cyclase type 2 (AC2) in non-lipid raft domains of airway smooth muscle (ASM) cells, where they regulate specific cAMP-dependent responses. The goal of the present study was to identify the cellular microdomains where EP2 Rs stimulate cAMP production. EXPERIMENTAL APPROACH: FRET-based cAMP biosensors were targeted to different subcellular locations of primary human ASM cells...
June 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28596292/the-pde4-inhibitor-chf-6001-and-lamas-inhibit-bronchoconstriction-induced-remodelling-in-lung-slices
#7
Loes Em Kistemaker, Tjitske A Oenema, Hoeke A Baarsma, I Sophie T Bos, Martina Schmidt, Fabrizio Facchinetti, Maurizio Civelli, Gino Villetti, Reinoud Gosens
Background Combination therapy of PDE4 inhibitors and anticholinergics induces bronchoprotection in COPD. Mechanical forces that arise during bronchoconstriction may contribute to airway remodelling. Therefore, we investigated the impact of PDE4 inhibitors and anticholinergics on bronchoconstriction-induced remodelling. Because of the different mechanism of action of PDE4 inhibitors and anticholinergics, we hypothesized functional interactions of these two drug classes. Methods Guinea pig precision cut lung slices were pre-incubated with the PDE4-inhibitors CHF-6001 or roflumilast and/or the anticholinergics tiotropium or glycopyorrolate, followed by stimulation with methacholine (10 μM) or TGF -β1 (2 ng/mL) for 48 hours...
June 8, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28558784/hesperetin-5-7-3-o-triacetate-suppresses-airway-hyperresponsiveness-in-ovalbumin-sensitized-and-challenged-mice-without-reversing-xylazine-ketamine-induced-anesthesia-in-normal-mice
#8
You-Lan Yang, Chi-Li Chen, Chi-Ming Chen, Wun-Chang Ko
BACKGROUND: We recently reported that hesperetin-5,7,3'-O-triacetate (HTA) dually inhibited phosphodiesterase (PDE)3/4 with a therapeutic ratio of 20.8. The application and development of PDE4 inhibitors for treating asthma or COPD are limited by their side effects, such as nausea, vomiting and gastric hypersecretion. PDE4 inhibitors were reported to reverse xylazine/ketamine-induced anesthesia in rats and triggered vomiting in ferrets. Thus the reversing effect of HTA on xylazine/ketamine-induced anesthesia in mice was studied to assess emetic effect of HTA...
May 30, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28554321/phosphodiesterase-4-inhibitors-in-immune-mediated-diseases-mode-of-action-clinical-applications-current-and-future-perspectives
#9
Lazaros I Sakkas, Athanasios Mavropoulos, Dimitrios P Bogdanos
Phosphodiesterase (PDE) 4 is a superfamily of enzymes that catalyze the hydrolysis of cyclic adenosine 3',5'-monophosphate (cAMP), an intracellular second messenger and regulator of a wide array of genes and proteins. Increased levels of intracellular cAMP lead to activation of genes but also to inhibition of nuclear factor-kappa B, involved in pro-inflammatory responses. By increasing cAMP levels, PDE4 inhibitors, such as apremilast, reduced production of pro-inflammatory TNFα, IFNγ, and IL-17 and increased production of anti-inflammatory IL-10 in lipopolysaccharide-stimulated peripheral blood mononuclear cells, and in patients with psoriatic arthritis (PsA)...
May 29, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28523172/roles-of-roflumilast-a-selective-phosphodiesterase-4-inhibitor-in-airway-diseases
#10
REVIEW
Theerasuk Kawamatawong
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases. Both diseases have incompletely distinct pathophysiology, clinical manifestation, and treatment responsiveness. Pulmonary and systemic inflammations are the hallmarks of COPD. Most asthma responds to inhaled corticosteroid (ICS) treatment. In contrast, COPD is a corticosteroid-resistant disease. Bronchodilators are a preferred treatment method of COPD, with the aim of improving symptoms and preventing exacerbation...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28515693/rolipram-improves-outcome-in-a-rat-model-of-infant-sepsis-induced-cardiorenal-syndrome
#11
Clark R Sims, Sharda P Singh, Shengyu Mu, Neriman Gokden, Dala Zakaria, Trung C Nguyen, Philip R Mayeux
While the mortality rate associated with sepsis in children has fallen over the years, it still remains unacceptably high. The development of both acute cardiac dysfunction and acute kidney injury during severe sepsis is categorized as type 5 cardiorenal syndrome (CRS) and is poorly understood in infants. To address this lack of understanding and the need for an appropriate animal model in which to conduct relevant preclinical studies, we developed a model of infant sepsis-induced CRS in rat pups then evaluated the therapeutic potential of the phosphodiesterase (PDE) 4 inhibitor, rolipram...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28499587/the-phosphodiesterase-4-inhibitor-apremilast-inhibits-th1-but-promotes-th17-responses-induced-by-6-sulfo-lacnac-slan-dendritic-cells
#12
Stephanie Oehrl, Hridayesh Prakash, Annette Ebling, Nina Trenkler, Priscila Wölbing, Anja Kunze, Thomas Döbel, Marc Schmitz, Alexander Enk, Knut Schäkel
BACKGROUND: The phosphodiesterase 4 (PDE4) inhibitor apremilast increases cellular cAMP levels and has proven effective in the treatment of psoriasis and psoriasis arthritis. We recently described 6-sulfo LacNAc dendritic cells (slanDCs) as immature DCs in blood and as a subset of inflammatory dermal DCs in psoriasis with a pronounced capacity to produce proinflammatory cytokines and to program Th17/Th1 T cell responses. OBJECTIVE: The aim of this study was to investigate possible immune regulatory effects of the PDE4 inhibitor apremilast on slanDCs...
April 20, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28497801/pde4-inhibition-restores-the-balance-between-excitation-and-inhibition-in-vta-dopamine-neurons-disrupted-by-repeated-in-vivo-cocaine-exposure
#13
Xiaojie Liu, Peng Zhong, Casey Vickstrom, Yan Li, Qing-Song Liu
Phosphodiesterase type 4 (PDE4) is a family of enzymes that selectively degrade intracellular cAMP. PDE4 inhibitors have been shown to regulate the rewarding and reinforcing effects of cocaine, but the underlying mechanisms remain poorly understood. Here we show that pretreatments with the PDE4 inhibitor rolipram attenuated cocaine-induced locomotor sensitization in mice. Repeated cocaine exposure in vivo caused a decrease in inhibitory postsynaptic currents (IPSCs) and an increase in the AMPAR/NMDAR ratio in ventral tegmental area (VTA) dopamine neurons in midbrain slices ex vivo...
May 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28492291/crisaborole-phosphodiesterase-inhibitor-for-treatment-of-atopic-dermatitis
#14
D M Paton
Atopic dermatitis (AD) is an extremely common condition affecting as many as 10-20% of children and 2-10% of adults. A particularly distressing symptom of AD is pruritus. One of the important aspects of AD is inflammation associated with increased activity of phosphodiesterase 4 (PDE4), resulting in decreased intracellular levels of cyclic adenosine monophosphate, which in turn causes increased production of inflammatory cytokines. Crisaborole was developed as a small-molecule, boron-based, selective PDE4 inhibitor that can be used topically...
April 2017: Drugs of Today
https://www.readbyqxmd.com/read/28485811/the-effects-of-second-messenger-camp-and-its-relative-components-on-the-contraction-of-uterine-smooth-muscle-of-rat
#15
S-J Shu, X-G Lei, J-H Liang, Y-H Song, Q Xu, X-D Chen, L-G Mao, Z-G Li
OBJECTIVE: To investigate the effect of second messenger pathways on the uterine smooth muscle contraction and their associated mechanisms, and compare the evaluation methods. MATERIALS AND METHODS: Preparation of uterine smooth muscle strips from healthy pregnant 18-21 d SD and non-pregnant rats. When the contraction of muscle strips was stable, we conducted gradient administration: PDE4 inhibitors (Z90), prostaglandin PGE2, adenylate cyclase inhibitor (SQ 22,530), cAMP analogs (dbcAMP) and AMPK agonists (AICAR), solvent dimethyl sulfoxide (DMSO) as controlled...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28477089/the-phosphodiesterase-4-inhibitor-roflumilast-decreases-ethanol-consumption-in-c57bl-6j-mice
#16
Xin Liu, Pi-Da Hao, Ming-Feng Yang, Jing-Yi Sun, Lei-Lei Mao, Cun-Dong Fan, Zong-Yong Zhang, Da-Wei Li, Xiao-Yi Yang, Bao-Liang Sun, Han-Ting Zhang
RATIONALE: Alcohol use disorders have become one of the most damaging psychiatric disorders in the world; however, there are no ideal treatments in clinic. Phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes intracellular cyclic AMP (cAMP), has been involved in alcohol use disorders. Roflumilast is the first PDE4 inhibitor approved for treatment of chronic obstructive pulmonary diseases in clinic. It was of particular interest to researchers to determine whether roflumilast altered ethanol consumption...
May 6, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28451841/roflumilast-reduces-cerebral-inflammation-in-a-rat-model-of-experimental-subarachnoid-hemorrhage
#17
Qingjian Wu, Lifeng Qi, Hanxia Li, Leilei Mao, Mingfeng Yang, Rongxia Xie, Xiaoyi Yang, Jian Wang, Zongyong Zhang, Jiming Kong, Baoliang Sun
Roflumilast, a selective inhibitor for PDE4, is approved by FDA as an anti-inflammation drug for treatment of chronic obstructive pulmonary disease (COPD). This study investigates the effects of roflumilast on cerebral inflammation in the rat SAH model. Here, we show that subcutaneous administration of roflumilast (3 mg/kg) significantly improved the neurological deficits. Measurement of evans blue extravasation and brain water content revealed a significant reduction of blood-brain barrier permeability and brain edema...
April 27, 2017: Inflammation
https://www.readbyqxmd.com/read/28450469/novel-phosphodiesterase-4-inhibitor-fcpr03-alleviates-lipopolysaccharide-induced-neuroinflammation-by-regulation-of-the-camp-pka-creb-signaling-pathway-and-nf-%C3%AE%C2%BAb-inhibition
#18
Zheng-Qiang Zou, Jia-Jia Chen, Hong-Fang Feng, Yu-Fang Cheng, Hai-Tao Wang, Zhong-Zhen Zhou, Hai-Biao Guo, Wenhua Zheng, Jiang-Ping Xu
Overactivation of microglia contributes to the induction of neuroinflammation, which is highly involved in the pathology of many neurodegenerative diseases. Phosphodiesterase 4 (PDE4) represents a promising therapeutic target for anti-inflammation; however, the dose-limiting side effects, such as nausea and emesis, have impeded their clinic application. FCPR03, a novel selective PDE4 inhibitor synthesized in our laboratory, shows little or no emetic potency; however, the anti-inflammatory activities of FCPR03 in vitro and in vivo and the molecular mechanisms are still not clearly understood...
July 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28438557/the-isozyme-selective-phosphodiesterase-4-inhibitor-abi-4-attenuates-the-effects-of-lipopolysaccharide-in-human-cells-and-rodent-models-of-peripheral-and-cns-inflammation
#19
Joseph R Hedde, Ashley N Hanks, Christopher J Schmidt, Zoë A Hughes
Inhibitors of phosphodiesterase-4 (PDE4) have been approved for the treatment of inflammatory disorders, but are associated with dose-limiting nausea and vomiting. These side effects are hypothesized to be mediated by inhibition of the PDE4D isozyme. Here we demonstrate the anti-inflammatory effects of the novel brain penetrant PDE4D-sparing PDE4 inhibitor, ABI-4. ABI-4 was a potent (EC50∼14nM) inhibitor of lipopolysaccharide (LPS) induced TNF-α release from mouse microglia and human PBMCs. ABI-4 (0.32mg/kg) blocked LPS-induced release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in blood and brain of mice...
April 23, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28432317/psiguajadials-a-k-unusual-psidium-meroterpenoids-as-phosphodiesterase-4-inhibitors-from-the-leaves-of-psidium-guajava
#20
Gui-Hua Tang, Zhen Dong, Yan-Qiong Guo, Zhong-Bin Cheng, Chu-Jun Zhou, Sheng Yin
Bioassay-guided fractionation of the ethanolic extract of the leaves of Psidium guajava led to the isolation of 11 new Psidium meroterpenoids, psiguajadials A-K (1-11), along with 17 known ones (12-28). Their structures and absolute configurations were elucidated by spectroscopic methods and comparison of experimental and calculated ECD. Compounds 1 and 2 represent two unprecedented skeletons of 3,5-diformyl-benzyl phloroglucinol-coupled sesquiterpenoid, while 3 is the first example of Psidium meroterpenoids coupling via an oxepane ring...
April 21, 2017: Scientific Reports
keyword
keyword
85204
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"