556 results match your criteria Acta pharmaceutica Sinica. B[Journal]


Anti-RAS drugs and SARS-CoV-2 infection.

Acta Pharm Sin B 2020 Apr 28. Epub 2020 Apr 28.

Department of Pharmacy, Peking University Third Hospital, Beijing 100083, China.

•There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation.•The level of ACE2 expression is not completely related with the risk of COVID-19 infection.•There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195321PMC

Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites.

Acta Pharm Sin B 2020 Apr 20. Epub 2020 Apr 20.

Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, China.

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually led to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194921PMC

biosynthesis of liquiritin in .

Acta Pharm Sin B 2020 Apr 23;10(4):711-721. Epub 2019 Jul 23.

School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 102488, China.

Liquiritigenin (LG), isoliquiritigenin (Iso-LG), together with their respective glycoside derivatives liquiritin (LN) and isoliquiritin (Iso-LN), are the main active flavonoids of , which is arguably the most widely used medicinal plant with enormous demand on the market, including Chinese medicine prescriptions, preparations, health care products and even food. Pharmacological studies have shown that these ingredients have broad medicinal value, including anti-cancer and anti-inflammatory effects. Although the biosynthetic pathway of glycyrrhizin, a triterpenoid component from , has been fully analyzed, little attention has been paid to the biosynthesis of the flavonoids of this plant. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161706PMC

Targeted delivery of hyaluronic acid nanomicelles to hepatic stellate cells in hepatic fibrosis rats.

Acta Pharm Sin B 2020 Apr 18;10(4):693-710. Epub 2019 Jul 18.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610064, China.

Hepatic fibrosis is one kind of liver diseases with a high mortality rate and incidence. The activation and proliferation of hepatic stellate cells (HSCs) is the most fundamental reason of hepatic fibrosis. There are no specific and effective drug delivery carriers for the treatment of hepatic fibrosis at present. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.07.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161713PMC

Effect of fluid shear stress on the internalization of kidney-targeted delivery systems in renal tubular epithelial cells.

Acta Pharm Sin B 2020 Apr 22;10(4):680-692. Epub 2019 Nov 22.

Key Laboratory of Drug-Targeting and Drug Delivery Systems of Ministry of Education and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

Renal tubular epithelial cells (RTECs) are important target cells for the development of kidney-targeted drug delivery systems. Under physiological conditions, RTECs are under constant fluid shear stress (FSS) from original urine in the renal tubule and respond to changes of FSS by altering their morphology and receptor expression patterns, which may affect reabsorption and cellular uptake. Using a microfluidic system, controlled shear stress was applied to proximal tubule epithelial cell line HK-2. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161666PMC

Combinatory antitumor therapy by cascade targeting of a single drug.

Acta Pharm Sin B 2020 Apr 5;10(4):667-679. Epub 2019 Sep 5.

Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China.

Combination therapy has shown its promise in the clinic for enhancing the efficacy of tumor treatment. However, the dose control of multiple drugs and their non-overlapping toxicity from different drugs are still great challenge. In this work, a single model drug, paclitaxel (PTX), is used to realize combination therapy and solve the problems mentioned above. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161707PMC

Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease.

Acta Pharm Sin B 2020 Apr 29;10(4):646-666. Epub 2019 Jul 29.

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

Drug repurposing is an efficient strategy for new drug discovery. Our latest study found that nitazoxanide (NTZ), an approved anti-parasite drug, was an autophagy activator and could alleviate the symptom of Alzheimer's disease (AD). In order to further improve the efficacy and discover new chemical entities, a series of NTZ-based derivatives were designed, synthesized, and evaluated as autophagy activator against AD. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161708PMC

Synthesis, and biological evaluation of novel lappaconitine derivatives as potential anti-inflammatory agents.

Acta Pharm Sin B 2020 Apr 13;10(4):628-645. Epub 2019 Sep 13.

Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China.

Lappaconitine (LA), a natural compound with a novel C18-diterpenoid alkaloid skeleton, displayed extensive biological profile. Recent research on LA is focused mainly on its anti-tumor and analgesic effects, and therefore we aimed to investigate its anti-inflammatory potential. A series of novel LA derivatives with various substituents on the 20-N position was designed and synthesized. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161710PMC

Class I histone deacetylase inhibition is synthetic lethal with BRCA1 deficiency in breast cancer cells.

Acta Pharm Sin B 2020 Apr 5;10(4):615-627. Epub 2019 Sep 5.

Cancer Centre, Faculty of Health Sciences, University of Macau, Macau SAR, China.

Breast cancer susceptibility gene 1 () is a tumor suppressor gene, which is frequently mutated in breast and ovarian cancers. BRCA1 plays a key role in the homologous recombination directed DNA repair, allowing its deficiency to act as a therapeutic target of DNA damaging agents. In this study, we found that inhibition of the class I histone deacetylases (HDAC) exhibited synthetic lethality with BRCA1 deficiency in breast cancer cells. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161709PMC

Identification of a novel PAK1 inhibitor to treat pancreatic cancer.

Acta Pharm Sin B 2020 Apr 16;10(4):603-614. Epub 2019 Dec 16.

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China.

Pancreatic cancer is one of the most aggressive cancers with poor prognosis and a low 5-year survival rate. The family of P21-activated kinases (PAKs) appears to modulate many signaling pathways that contribute to pancreatic carcinogenesis. In this work, we demonstrated that PAK1 is a critical regulator in pancreatic cancer cell growth. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161699PMC

Monoacylglycerol lipase inhibitors: modulators for lipid metabolism in cancer malignancy, neurological and metabolic disorders.

Authors:
Hui Deng Weimin Li

Acta Pharm Sin B 2020 Apr 18;10(4):582-602. Epub 2019 Oct 18.

Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Monoacylglycerol lipase (MAGL) is a serine hydrolase that plays a crucial role catalysing the hydrolysis of monoglycerides into glycerol and fatty acids. It links the endocannabinoid and eicosanoid systems together by degradation of the abundant endocannabinoid 2-arachidaoylglycerol into arachidonic acid, the precursor of prostaglandins and other inflammatory mediators. MAGL inhibitors have been considered as important agents in many therapeutic fields, including anti-nociceptive, anxiolytic, anti-inflammatory, and even anti-cancer. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161712PMC

Targeting autophagy-related protein kinases for potential therapeutic purpose.

Acta Pharm Sin B 2020 Apr 18;10(4):569-581. Epub 2019 Oct 18.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.

Autophagy, defined as a scavenging process of protein aggregates and damaged organelles mediated by lysosomes, plays a significant role in the quality control of macromolecules and organelles. Since protein kinases are integral to the autophagy process, it is critically important to understand the role of kinases in autophagic regulation. At present, intervention of autophagic processes by small-molecule modulators targeting specific kinases has becoming a reasonable and prevalent strategy for treating several varieties of human disease, especially cancer. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161711PMC

D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19.

Acta Pharm Sin B 2020 Apr 20. Epub 2020 Apr 20.

CAS Key Laboratory of Receptor Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19). For the purpose, we developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or / studies, the other is for identifying lead compounds against potential drug targets docking. This server has its unique features, (1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible; (2) all the potential ligand-binding sites with volume larger than 200 Å on a protein structure were identified for docking; (3) correlation information among some conformations or binding sites was annotated; (4) it is easily to be updated, and is accessible freely to public (https://www. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169934PMC

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19.

Acta Pharm Sin B 2020 Apr 20. Epub 2020 Apr 20.

Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with Corona Virus Disease 2019 (COVID-19), we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169892PMC

Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods.

Acta Pharm Sin B 2020 Feb 27. Epub 2020 Feb 27.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102550PMC
February 2020

A systematic strategy for screening therapeutic constituents of (Turcz) Baill infiltrated blood-brain barrier oriented in lesions using ethanol and water extracts: a novel perspective for exploring chemical material basis of herb medicines.

Acta Pharm Sin B 2020 Mar 30;10(3):557-568. Epub 2019 Oct 30.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of remains obscure. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049611PMC

Reimaging biological barriers affecting distribution and extravasation of PEG/peptide- modified liposomes in xenograft SMMC7721 tumor.

Acta Pharm Sin B 2020 Mar 2;10(3):546-556. Epub 2019 Jul 2.

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Liposomes, as one of the most successful nanotherapeutics, have a major impact on many biomedical areas. In this study, we performed laser scanning confocal microscope (LSCM) and immunohistochemistry (IHC) assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptide-conjugated active targeting liposomes (GE11-TLs) in SMMC7721 xenograft model. According to classification of individual cell types in high resolution images, biodistribution of macrophages, tumor cells, cells with high epidermal growth factor receptor (EGFR) expression and interstitial matrix in tumor microenvironment, in addition, their impacts on intra-tumor penetration of GE11-TLs were estimated. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049609PMC

Targeting peptide-decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor.

Acta Pharm Sin B 2020 Mar 5;10(3):529-545. Epub 2019 Jun 5.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy of triple negative breast cancer. BL-RD was composed of phospholipids, apolipoprotein A1 mimetic peptide (PK22), targeting peptide-conjugated cytotoxic mertansine (RM) and photodynamic agents of DiIC18(5) (DiD). Read More

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http://dx.doi.org/10.1016/j.apsb.2019.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049576PMC

Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones as potential HIV-1 inhibitors.

Acta Pharm Sin B 2020 Mar 5;10(3):512-528. Epub 2019 Sep 5.

Key Laboratory of Medicinal Chemistry for Natural Resources, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming 650091, China.

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049619PMC

Novel small molecule retrograde transport blocker confers post-exposure protection against ricin intoxication.

Acta Pharm Sin B 2020 Mar 22;10(3):498-511. Epub 2019 Aug 22.

National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.

Ricin is a highly toxic type 2 ribosome-inactivating protein (RIP) which is extracted from the seeds of castor beans. Ricin is considered a potential bioterror agent and no effective antidote for ricin exists so far. In this study, by structural modification of a retrograde transport blocker Retro-2, a series of novel compounds were obtained. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049615PMC

Discovery of a highly selective VEGFR2 kinase inhibitor CHMFL-VEGFR2-002 as a novel anti-angiogenesis agent.

Acta Pharm Sin B 2020 Mar 18;10(3):488-497. Epub 2019 Oct 18.

High Magnetic Field Laboratory, Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.

Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049616PMC

Probiotics modulate the microbiota-gut-brain axis and improve memory deficits in aged SAMP8 mice.

Acta Pharm Sin B 2020 Mar 7;10(3):475-487. Epub 2019 Jul 7.

Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.

ProBiotic-4 is a probiotic preparation composed of , , , and . This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049608PMC

Benzydamine inhibits osteoclast differentiation and bone resorption down-regulation of interleukin-1 expression.

Acta Pharm Sin B 2020 Mar 8;10(3):462-474. Epub 2019 Nov 8.

Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, South Korea.

Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity, which is closely associated with inflammation. Benzydamine (BA) has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of pro-inflammatory cytokines or prostaglandins. However, its role in osteoclast differentiation and function remains unknown. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049613PMC

Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions.

Acta Pharm Sin B 2020 Mar 5;10(3):447-461. Epub 2019 Sep 5.

Laboratory of Anti-inflammation and Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Ulcerative colitis (UC) manifests as an etiologically complicated and relapsing gastrointestinal disease. The enteric nervous system (ENS) plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract. Berberine, an isoquinoline alkaloid, is known as its anti-inflammatory and therapeutic effects in experimental colitis. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049614PMC

Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent.

Acta Pharm Sin B 2020 Mar 14;10(3):434-446. Epub 2019 Aug 14.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049605PMC

Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity.

Acta Pharm Sin B 2020 Mar 3;10(3):414-433. Epub 2019 Sep 3.

Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, College of Polymer Science and Engineering, West China School of Pharmacy, Sichuan University, Chengdu 610064, China.

The T cell co-stimulatory molecule OX40 and its cognate ligand OX40L have attracted broad research interest as a therapeutic target in T cell-mediated diseases. Accumulating preclinical evidence highlights the therapeutic efficacy of both agonist and blockade of the OX40-OX40L interaction. Despite this progress, many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049610PMC

Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer.

Acta Pharm Sin B 2020 Mar 14;10(3):399-413. Epub 2019 Nov 14.

Department of Biochemistry, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor 42610, Malaysia.

Activated pancreatic stellate cells (PSCs) have been widely accepted as a key precursor of excessive pancreatic fibrosis, which is a crucial hallmark of chronic pancreatitis (CP) and its formidable associated disease, pancreatic cancer (PC). Hence, anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs. Most of the anti-fibrotic agents have been limited to phase I/II clinical trials involving vitamin analogs, which are abundant in medicinal plants and have proved to be promising for clinical application. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049637PMC

Disturbed Yin-Yang balance: stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1.

Acta Pharm Sin B 2020 Mar 22;10(3):383-398. Epub 2019 Jun 22.

Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, Jinan University, Guangzhou 510632, China.

Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, is able to establish a lifelong latent infection in the human host. Following primary replication in mucosal epithelial cells, the virus can enter sensory neurons innervating peripheral tissues nerve termini. The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny, and thus latency is established in the cell. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049575PMC

Whole-genome sequencing and analysis of the Chinese herbal plant .

Acta Pharm Sin B 2020 Feb 16;10(2):374-382. Epub 2019 Aug 16.

Hunan Engineering Technology Research Center of Veterinary Drugs, Hunan Agricultural University, Changsha 410128, China.

Background: () (2n = 2x = 16) is genus of flowering plants belonging to the Gelsemicaeae family.

Method: Here, a high-quality genome assembly using the Oxford Nanopore Technologies (ONT) platform and high-throughput chromosome conformation capture techniques (Hi-C) were used.

Results: A total of 56. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016290PMC
February 2020

knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity.

Acta Pharm Sin B 2020 Feb 23;10(2):358-373. Epub 2019 Jul 23.

School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Blocking the programmed death-ligand 1 (PD-L1) on tumor cells with monoclonal antibody therapy has emerged as powerful weapon in cancer immunotherapy. However, only a minority of patients presented immune responses in clinical trials. To develop an alternative treatment method based on immune checkpoint blockade, we designed a novel and efficient CRISPR-Cas9 genome editing system delivered by cationic copolymer aPBAE to downregulate PD-L1 expression on tumor cells specifically knocking out Cyclin-dependent kinase 5 () gene . Read More

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http://dx.doi.org/10.1016/j.apsb.2019.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016277PMC
February 2020

Improving the positional adaptability: structure-based design of biphenyl-substituted diaryltriazines as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.

Acta Pharm Sin B 2020 Feb 17;10(2):344-357. Epub 2019 Oct 17.

Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433 China.

In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016291PMC
February 2020

Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: total synthesis and discovery of potent MDR reversal agents.

Acta Pharm Sin B 2020 Feb 31;10(2):327-343. Epub 2019 Jul 31.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.

Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy . However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016283PMC
February 2020

Lineage reprogramming of fibroblasts into induced cardiac progenitor cells by CRISPR/Cas9-based transcriptional activators.

Acta Pharm Sin B 2020 Feb 17;10(2):313-326. Epub 2019 Sep 17.

Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.

Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types. Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs). CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016296PMC
February 2020

3--Acetyl-11-keto- -boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma.

Acta Pharm Sin B 2020 Feb 10;10(2):301-312. Epub 2020 Jan 10.

The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.

Glioblastoma is the most common and aggressive primary tumor in the central nervous system, accounting for 12%-15% of all brain tumors. 3--Acetyl-11-keto--boswellic acid (AKBA), one of the most active ingredients of gum resin from Birdw., was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016292PMC
February 2020

PCC0208017, a novel small-molecule inhibitor of MARK3/MARK4, suppresses glioma progression and .

Acta Pharm Sin B 2020 Feb 18;10(2):289-300. Epub 2019 Sep 18.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai 264005, China.

Gliomas are the most common primary intracranial neoplasms among all brain malignancies, and the microtubule affinity regulating kinases (MARKs) have become potential drug targets for glioma. Here, we report a novel dual small-molecule inhibitor of MARK3 and MARK4, designated as PCC0208017. PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferation in three glioma cell lines. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016295PMC
February 2020

A novel S1P1 modulator IMMH002 ameliorates psoriasis in multiple animal models.

Acta Pharm Sin B 2020 Feb 14;10(2):276-288. Epub 2019 Nov 14.

Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016294PMC
February 2020

Optimized functional and structural design of dual-target LMRAP, a bifunctional fusion protein with a 25-amino-acid antitumor peptide and GnRH Fc fragment.

Acta Pharm Sin B 2020 Feb 2;10(2):262-275. Epub 2019 Nov 2.

Shenyang Pharmaceutical University, Shenyang 110016, China.

To develop fusion protein of a GnRH Fc fragment and the integrin targeting AP25 antitumor peptide for GnRH receptor-expressing cancer therapy. The LMRAP fusion protein was constructed. A transwell invasion assay was performed. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016293PMC
February 2020

Abnormal metabolism of gut microbiota reveals the possible molecular mechanism of nephropathy induced by hyperuricemia.

Acta Pharm Sin B 2020 Feb 30;10(2):249-261. Epub 2019 Oct 30.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, China.

The progression of hyperuricemia disease is often accompanied by damage to renal function. However, there are few studies on hyperuricemia nephropathy, especially its association with intestinal flora. This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016297PMC
February 2020

Biomimetic carbon nanotubes for neurological disease therapeutics as inherent medication.

Acta Pharm Sin B 2020 Feb 6;10(2):239-248. Epub 2019 Nov 6.

Translational Medicine Center, Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China.

Nowadays, nanotechnology is revolutionizing the approaches to different fields from manufacture to health. Carbon nanotubes (CNTs) as promising candidates in nanomedicine have great potentials in developing novel entities for central nervous system pathologies, due to their excellent physicochemical properties and ability to interface with neurons and neuronal circuits. However, most of the studies mainly focused on the drug delivery and bioimaging applications of CNTs, while neglect their application prospects as therapeutic drugs themselves. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016289PMC
February 2020

Degradation of proteins by PROTACs and other strategies.

Acta Pharm Sin B 2020 Feb 13;10(2):207-238. Epub 2019 Aug 13.

Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.

Blocking the biological functions of scaffold proteins and aggregated proteins is a challenging goal. PROTAC proteolysis-targeting chimaera (PROTAC) technology may be the solution, considering its ability to selectively degrade target proteins. Recent progress in the PROTAC strategy include identification of the structure of the first ternary eutectic complex, extra-terminal domain-4-PROTAC-Von-Hippel-Lindau (BRD4-PROTAC-VHL), and PROTAC ARV-110 has entered clinical trials for the treatment of prostate cancer in 2019. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016280PMC
February 2020

PXR: a center of transcriptional regulation in cancer.

Acta Pharm Sin B 2020 Feb 29;10(2):197-206. Epub 2019 Jun 29.

Department of Pharmacology, Shantou University Medical College, Shantou 515041, China.

Pregnane X receptor (PXR, NR1I2) is a prototypical member of the nuclear receptor superfamily. PXR can be activated by both endobiotics and xenobiotics. As a key xenobiotic receptor, the cellular function of PXR is mostly exerted by its binding to the regulatory gene sequences in a ligand-dependent manner. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016272PMC
February 2020

The 3'-untranslated region contributes to the pregnane X receptor (PXR) expression down-regulation by PXR ligands and up-regulation by glucocorticoids.

Acta Pharm Sin B 2020 Jan 21;10(1):136-152. Epub 2019 Oct 21.

Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove CZ-500 05, Czech Republic.

Pregnane X receptor (PXR) is the major regulator of xenobiotic metabolism. PXR itself is controlled by various signaling molecules including glucocorticoids. Moreover, negative feed-back regulation has been proposed at the transcriptional level. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976988PMC
January 2020

New insights of CYP1A in endogenous metabolism: a focus on single nucleotide polymorphisms and diseases.

Acta Pharm Sin B 2020 Jan 2;10(1):91-104. Epub 2019 Dec 2.

Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai 200051, China.

Cytochrome P450 1A (CYP1A), one of the major CYP subfamily in humans, not only metabolizes xenobiotics including clinical drugs and pollutants in the environment, but also mediates the biotransformation of important endogenous substances. In particular, some single nucleotide polymorphisms (SNPs) for genes may affect the metabolic ability of endogenous substances, leading to some physiological or pathological changes in humans. This review first summarizes the metabolism of endogenous substances by CYP1A, and then introduces the research progress of SNPs, especially the research related to human diseases. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984740PMC
January 2020

The gut microbiome: an orchestrator of xenobiotic metabolism.

Acta Pharm Sin B 2020 Jan 10;10(1):19-32. Epub 2019 Dec 10.

Department of Veterinary and Biomedical Science, the Pennsylvania State University, University Park, PA 16802, USA.

Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic metabolism. The gut microbiome, the collection of microorganisms in the gastrointestinal tract, can alter the metabolic outcome of pharmaceuticals, environmental toxicants, and heavy metals, thereby changing their pharmacokinetics. Direct chemical modification of xenobiotics by the gut microbiome, either through the intestinal tract or re-entering the gut enterohepatic circulation, can lead to increased metabolism or bioactivation, depending on the enzymatic activity within the microbial niche. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6984741PMC
January 2020

Insulin-like growth factor 1 modulates the phosphorylation, expression, and activity of organic anion transporter 3 through protein kinase A signaling pathway.

Acta Pharm Sin B 2020 Jan 5;10(1):186-194. Epub 2019 Jun 5.

Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.

Organic anion transporter 3 (OAT3) plays a vital role in removing a broad variety of anionic drugs from kidney, thus avoiding their possible toxicity in the body. In the current study, we investigated the role of insulin-like growth factor 1 (IGF-1) in the regulation of OAT3. We showed that IGF-1 induced a dose- and time-dependent increase in OAT3 transport activity, which correlated well with an increase in OAT3 expression. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977015PMC
January 2020

Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice.

Acta Pharm Sin B 2020 Jan 28;10(1):171-185. Epub 2019 Nov 28.

Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.

The prevalence of obesity-associated conditions raises new challenges in clinical medication. Although altered expression of drug-metabolizing enzymes (DMEs) has been shown in obesity, the impacts of obese levels (overweight, obesity, and severe obesity) on the expression of DMEs have not been elucidated. Especially, limited information is available on whether parental obese levels affect ontogenic expression of DMEs in children. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976990PMC
January 2020

Bioengineered miR-328-3p modulates GLUT1-mediated glucose uptake and metabolism to exert synergistic antiproliferative effects with chemotherapeutics.

Acta Pharm Sin B 2020 Jan 7;10(1):159-170. Epub 2019 Nov 7.

Department of Biochemistry & Molecular Medicine, UC Davis School of Medicine, Sacramento 95817, CA, USA.

MicroRNAs (miRNAs or miRs) are small noncoding RNAs derived from genome to control target gene expression. Recently we have developed a novel platform permitting high-yield production of bioengineered miRNA agents (BERA). This study is to produce and utilize novel fully-humanized BERA/miR-328-3p molecule (hBERA/miR-328) to delineate the role of miR-328-3p in controlling nutrient uptake essential for cell metabolism. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976971PMC
January 2020

Effects of total parenteral nutrition on drug metabolism gene expression in mice.

Acta Pharm Sin B 2020 Jan 6;10(1):153-158. Epub 2019 Nov 6.

Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.

Parenteral nutrition-associated liver disease (PNALD) is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition (TPN). Omega-6 rich Intralipid® and omega-3 rich Omegaven® are two intravenous lipid emulsions used in TPN. TPN could affect the hepatic expression of genes in anti-oxidative stress, but it's unknown whether TPN affects genes in drug metabolism. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976970PMC
January 2020

Hepatic and intestinal biotransformation gene expression and drug disposition in a dextran sulfate sodium-induced colitis mouse model.

Acta Pharm Sin B 2020 Jan 12;10(1):123-135. Epub 2019 Dec 12.

Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA.

We examined the impact of gut inflammation on the expression of cytochrome P450 (P450) and other biotransformation genes in male mice using a dextran sulfate sodium (DSS)-induced colitis model. Several P450 isoforms, including CYP1A, CYP2B, CYP2C, and CYP3A, were down-regulated, accompanied by decreases in microsomal metabolism of diclofenac and nifedipine, in the liver and small intestine. The impact of the colitis on clearance of oral drugs varied for four different drugs tested: a small decrease for nifedipine, a relatively large decrease for lovastatin, but no change for pravastatin, and a large decrease in the absorption of cyclosporine A. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6976992PMC
January 2020