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Drug Design, Development and Therapy

Xiao-Dong Li, Yu-Peng Wu, Shao-Hao Chen, Ying-Chun Liang, Ting-Ting Lin, Tian Lin, Yong Wei, Xue-Yi Xue, Qing-Shui Zheng, Ning Xu
Purpose: To examine the effects and mechanism of action of fasudil on cytoskeletal polymerization, collagen synthesis, and apoptosis in fibroblasts derived from human urethral scar tissue. Materials and methods: Fibroblasts treated with or without transforming growth factor β1 (TGF-β1, 10 ng/mL) were incubated with fasudil (12.5, 25, 50 μmol/L) for 24 hours. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression of Arp2, Arp3, WASP, and WAVE2...
2018: Drug Design, Development and Therapy
Jia-Chuan Li, Xiao-Fei Shen, Jun-Ao Shao, Meng-Min Tao, Jian Gu, Jingyu Li, Ning Huang
Background: Coptis chinensis Franch is extensively used in traditional Chinese medicine to treat diabetes and dementia. Alkaloids are the main active ingredients of C. chinensis . Purpose: This study was designed to probe the effects and possible mechanisms of the total alkaloids from C. chinensis (TAC) on cognitive deficits in type 2 diabetic rats. Methods: Cognitive deficits were induced in rats by streptozotocin and high glucose/high fat diet...
2018: Drug Design, Development and Therapy
Peter Dogterom, Robert Riesenberg, Rik de Greef, Justin Dennie, Martin Johnson, Venkatesh Pilla Reddy, André Mm Miltenburg, Robert L Findling, Abhijeet Jakate, Timothy J Carrothers, Matthew D Troyer
Purpose: This study aimed to characterize the pharmacokinetic (PK) properties, safety, and tolerability of asenapine, and to develop a population PK model in pediatric patients with schizophrenia, bipolar disorder, or other psychiatric disorders. Methods: Two Phase I multiple ascending-dose studies were conducted to evaluate the PK, safety, and tolerability of sublingual asenapine in pediatric patients (age 10-17 years) with schizophrenia or bipolar I disorder. Patients received asenapine 1-10 mg twice daily for up to 12 days...
2018: Drug Design, Development and Therapy
Andrea Romigi, Giuseppe Vitrani, Temistocle Lo Giudice, Diego Centonze, Valentina Franco
Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness and rapid eye movement sleep dysregulation, manifesting as cataplexy and sleep paralysis, as well as hypnagogic and hypnopompic hallucinations. Disease onset may occur at any age, although adolescents and young adults are mainly affected. Currently, the diagnosis delay ranges from 8 to 10 years and drug therapy may only attenuate symptoms. Pitolisant is a first-in-class new drug currently authorized by the European Medicines Agency to treat narcolepsy with or without cataplexy in adults and with an expanded evaluation for the treatment of neurologic diseases such as Parkinson's disease and epilepsy...
2018: Drug Design, Development and Therapy
Yuan-Yuan Zhao, Ying Tian, Lin Liu, Jian-Hua Zhan, Xue Hou, Xi Chen, Ting Zhou, Yan Huang, Li Zhang
Aim: Our previous research showed that AKT inactivation via small molecule inhibitors did not induce significant apoptosis, but rather markedly increased autophagy in nasopharyngeal carcinoma (NPC). The purpose of the current study was to determine whether autophagy inhibition can enhance the anticancer efficacy of an AKT inhibitor (MK-2206). Materials and methods: NPC cell lines CNE-2 (Epstein-Barr virus negative) and C666-1 (Epstein-Barr virus positive) were used to conduct the research...
2018: Drug Design, Development and Therapy
Yue Liu, Yanlan Wang, Jieyu Xing, Yumei Li, Jiayu Liu, Zhong Wang
Introduction: Interleukin-15 (IL-15) is an immunomodulatory cytokine. It can activate and expand cytotoxic CD8 T lymphocytes and natural killer cells, leading to potent antitumor effects. Various forms of IL-15 are now in different stages of development for cancer immunotherapy. One of the major issues with IL-15 or IL15-IL15Rα fusion is high toxicity due to systemic activation of immune cells. Materials and methods: In this study, we engineered a nanobody-cytokine fusion molecule, anti-CEA-IL15, in which an anti-CEA nanobody was linked to an IL15Rα-IL15 fusion...
2018: Drug Design, Development and Therapy
Mehdi Ranjbar, Abbas Pardakhty, Arezou Amanatfard, Ali Asadipour
Metal-organic frameworks (MOFs) are structures made up of inorganic nodes, which can be either single ions or clusters of ions and organic linkers. This study reports on a novel processing route for producing β-estradiol encapsulated in Zn-MOF nanocomposites by microwave-assisted coprecipitation as a facile and fast method. Zn-MOF nanocomposites were synthesized with the aid of Zn(OAc)2 ⋅2H2 O and 2,6-pyridine dicarboxylic acid ammonium as an organic ligand. Furthermore, we studied encapsulated β-estradiol which is one of the most important classes of estrogenic compounds that are used in the treatment of prostate cancer and breast cancer...
2018: Drug Design, Development and Therapy
Tanveer A Wani, Ahmed H Bakheit, Mohammed Nazam Ansari, Abdul-Rahman A Al-Majed, Bakr M Al-Qahtani, Seema Zargar
Background: The binding interaction between bovine serum albumin (BSA) and roflumilast (ROF) was explored in this study. The binding of drugs to albumin plays a vital role in their pharmacokinetics and pharmacodynamics in vivo. The mechanisms involved in the interaction between BSA and ROF was studied using multi-spectroscopic experimental and computational approaches. Materials and methods: Spectrofluorometric experiments were used to determine the method of quenching involved and the conformational changes in the BSA...
2018: Drug Design, Development and Therapy
Jahangir Khan, Sajid Bashir, Muhammad Asif Khan, Mohammad Amin Mohammad, Mohammad Isreb
Purpose: Dexibuprofen is an enantiomer of ibuprofen with low bioavailability which results from its hydrophobic nature. Nanosuspensions have developed a podium to solve the in vitro dissolution problem that frequently occurs in current research. Materials and methods: The drug and polymer solutions were mixed in a microchannel fluid reactor and the successive embryonic nanosuspension was decanted into a vial having the polymer solution. The impact of different process and formulation parameters including inlet angle, antisolvent and solvent flow rate(s), mixing time, drug concentration, polymer type and concentration was evaluated...
2018: Drug Design, Development and Therapy
Giuseppe Derosa, Giovanni Gaudio, Gianfranco Pasini, Angela D'Angelo, Pamela Maffioli
Aim: The aim of this study was to evaluate the effects of canrenone compared to hydrochlorothiazide (HCTZ) added to angiotensin II receptor blockers (ARBs) on glycemia, lipid profile, potassium, aldosterone and renal function in patients with hypertension and type 2 diabetes mellitus. Patients and methods: The study enrolled 182 Caucasian patients with hypertension and type 2 diabetes mellitus. Patients were already taking ARBs and were randomized to canrenone, 50 mg once a day, or HCTZ, 12...
2018: Drug Design, Development and Therapy
Hong Zhou, Haixin Qian
Objective: The aim of this study was to develop pH sensitive nanoparticles of budesonide for the treatment of ulcerative colitis. Methods: The NPs system was characterized by the transmission electron microscopy (TEM), particle size, drug loading and encapsulation efficiency. In addition, in vitro drug release prop-erties and pharmacokinetics were also investigated in detail. The optimized formulation was examined for its in-vivo targeting potential using 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in a rat model...
2018: Drug Design, Development and Therapy
Ziliang Ye, Haili Lu, Qiang Su, Manyun Long, Lang Li
Background: Previous studies have indicated that nicorandil can reduce perioperative myocardial injury (PMI) in patients undergoing elective percutaneous coronary intervention (ePCI), but this conclusion is still controversial. Additionally, studies reporting on the safety of nicorandil are lacking. Therefore, we performed this prospective study to evaluate the efficacy and safety of nicorandil on PMI in patients undergoing ePCI. Methods: One hundred and forty-six patients with coronary heart disease (CHD) scheduled to undergo ePCI were randomly assigned to the nicorandil group (n=74) or control group (n=72)...
2018: Drug Design, Development and Therapy
Günter Krause, Floyd Hassenrück, Michael Hallek
On the occasion of its recent approval for relapsed follicular lymphoma, we review the design and development of the pan-class I PI3K inhibitor copanlisib as a drug for the treatment of B-cell malignancies in comparison with other kinase inhibitors targeting B-cell-receptor signaling, in particular with strictly isoform-δ-selective idelalisib. In agreement with previously defined PI3K-inhibitor chemotypes, the 2,3-dihydroimidazo[1,2- c ]quinazoline scaffold of copanlisib adopts a flat conformation in the adenine-binding pocket of the catalytic p110 subunit and further extends into a deeper-affinity pocket in contrast to idelalisib, the quinazoline moiety of which is accommodated in a newly created selectivity pocket...
2018: Drug Design, Development and Therapy
Yanzi Guo, Yonghao Huang, Shuhong Tian, Xueli Xie, Guilan Xing, Jian Fu
Objectives: Calcineurin B (CNB) is a regulatory subunit of calcineurin, and it has antitumor activity. In this study, we aimed to investigate the effect of recombinant human calcineurin B (rhCNB) on the proliferation of gastric cancer cells and hepatoma cells both in vitro and in vivo. Materials and methods: Cell viability and cell proliferation were detected by MTT and BrdU assay. Flow cytometry, Western blot and immunohistochemistry were performed to determine rhCNB-induced apoptosis and cell cycle arrest...
2018: Drug Design, Development and Therapy
Saro Sarkisian, Diwakar Davar
Melanoma is increasing rapidly in incidence and prevalence, especially in younger females and older males. Treatment options have expanded beyond high-dose interleukin 2 and adoptive T-cell therapy to include inhibitors of immune checkpoints programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and small molecular inhibitors of pathways activated in melanoma, in particular the mitogen-activated protein kinase (MAPK) pathway. PD-1/CTLA-4 inhibitors and inhibitors of MAPK such as BRAF/MEK inhibitors have significantly improved survival in both the metastatic and, more recently, adjuvant settings...
2018: Drug Design, Development and Therapy
Zachary A King, Kevin N Sheth, W Taylor Kimberly, J Marc Simard
Glyburide (also known as glibenclamide) is a second-generation sulfonylurea drug that inhibits sulfonylurea receptor 1 (Sur1) at nanomolar concentrations. Long used to target KATP (Sur1-Kir6.2) channels for the treatment of diabetes mellitus type 2, glyburide was recently repurposed to target Sur1-transient receptor potential melastatin 4 (Trpm4) channels in acute central nervous system injury. Discovered nearly two decades ago, SUR1-TRPM4 has emerged as a critical target in stroke, specifically in large hemispheric infarction, which is characterized by edema formation and life-threatening brain swelling...
2018: Drug Design, Development and Therapy
Tivadar Bíró, Gabriella Horvát, Mária Budai-Szűcs, Erzsébet Csányi, Edit Urbán, Andrea Facskó, Piroska Szabó-Révész, Ildikó Csóka, Zoltán Aigner
Purpose: The formulation of topical ophthalmic products with appropriate therapeutic effect and patient compliance is a major challenge. To increase the efficiency of the ocular delivery of the drug, the enhancement of water solubility and the contact time of the drug on the surface of the cornea are necessary. In this work, prednisolone (PR)-containing eye drops were formulated with antimicrobial, mucoadhesive biopolymer and PR-cyclodextrin inclusion complex. This approach can be used for the development of innovative ophthalmic formulations...
2018: Drug Design, Development and Therapy
Bryce M Warner, David Safronetz, Derek R Stein
Lassa virus (LASV) is a rodent-borne arenavirus endemic to several West African countries that causes Lassa fever (LF). LF is typically mild but it can cause severe disease characterized by hemorrhagic fever and multi-organ failure. A current outbreak of LASV in Nigeria has seen greater than 300 cases with a case fatality rate of 22%. Currently, there are limited treatment options and no vaccine candidates are approved to prevent LASV infection. The Coalition for Epidemic Preparedness Innovations has identified LASV as an emerging pathogen of high consequence and this has resulted in a push for several preclinical vaccine candidates to be advanced toward clinical trials...
2018: Drug Design, Development and Therapy
Guojuan Zhang, Jianfang Zhang
Objective: Chronic kidney disease (CKD) is characterized by progressive loss of renal functions. At present, there are only limited therapeutic strategies to slow down the progress of CKD and there is an urgent need to develop new therapeutic strategies to treat CKD patients. Numerous research evidence supports the potential role of EGCG in the renal protection of CKD. However, the clinical use is still limited due to the poor oral bioavailability. The aim of this study was to develop pH-sensitive polymeric nanoparticles of EGCG to improve this deficiency...
2018: Drug Design, Development and Therapy
Jiang Fang, Handong Wang, Jian Zhou, Wei Dai, Yihao Zhu, Yuan Zhou, Xiaoliang Wang, Mengliang Zhou
Background: The neuroprotective effects of Baicalin have been confirmed in several central nervous system (CNS) diseases. However, its possible effect on traumatic brain injury (TBI) model is still not clear. The present study is aimed to investigate the role and the underling mechanisms of 7-D-glucuronic acid-5,6-dihydroxyflavone (Baicalin) on TBI model. Methods: The weight-drop model of TBI in Institute of Cancer Research mice was treated with Baicalin intraperitoneally at 30 minutes after TBI...
2018: Drug Design, Development and Therapy
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