Discovery of a Highly Selective VEGFR2 Kinase Inhibitor CHMFL-VEGFR2-002 as a Novel Anti-angiogenesis Agent
Publication date: Available online 18 October 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Zongru Jiang, Li Wang, Xuesong Liu, Cheng Chen, Beilei Wang, Wenliang Wang, Chen Hu, Kailin Yu, Ziping Qi, Qingwang Liu, Aoli Wang, Jing Liu, Guangchen Hong, Wenchao Wang, Qingsong LiuAbstractAngiogenesis 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 effect...
Source: Acta Pharmaceutica Sinica B - October 19, 2019 Category: Cancer & Oncology Source Type: research

PEP06 polypeptide 30 is a novel cluster-dissociating agent inhibiting αv integrin/FAK/SRC signaling in oral squamous cell carcinoma cells
This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent in vitro. Firstly, we found marked enrichment of αv integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of αv integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppres...
Source: Acta Pharmaceutica Sinica B - October 19, 2019 Category: Cancer & Oncology Source Type: research

Current Trends in Drug Metabolism and Pharmacokinetics
Publication date: Available online 18 October 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Yuhua Li, Qiang Meng, Meng biYang, Dongyang Liu, Xiangyu Hou, Lan Tang, Xin Wang, Yuanfeng Lyu, Xiaoyan Chen, Kexin Liu, Ai-Ming Yu, Zhong Zuo, Huichang BiAbstractPharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters ...
Source: Acta Pharmaceutica Sinica B - October 19, 2019 Category: Cancer & Oncology Source Type: research

Targeting autophagy-related protein kinases for potential therapeutic purpose
Publication date: Available online 18 October 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Honggang Xiang, Jifa Zhang, Congcong Lin, Lan Zhang, Bo Liu, Liang OuyangAbstractAutophagy, 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 bec...
Source: Acta Pharmaceutica Sinica B - October 19, 2019 Category: Cancer & Oncology Source Type: research

Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein
In this study, polymeric nanoparticles loaded with a baicalein–phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher di...
Source: Acta Pharmaceutica Sinica B - October 19, 2019 Category: Cancer & Oncology Source Type: research

Monoacylglycerol Lipase Inhibitors: Modulators for Lipid Metabolism in Cancer Malignancy, Neurological and Metabolic Disorders
Publication date: Available online 18 October 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Hui Deng, Weimin LiAbstractMonoacylglycerol 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-infl...
Source: Acta Pharmaceutica Sinica B - October 19, 2019 Category: Cancer & Oncology Source Type: research

Improving the positional adaptability: structure-based design of biphenyl-substituted diaryltriazines as novel non-nucleoside HIV-1 reverse transcriptase inhibitors
This article exhibited a novel series of biphenyl-substituted diaryltriazines (BP-DATAs) as HIV-1 reverse transcriptase inhibitors targeting nonnucleoside binding pocket (NNIBP) to improve the positional adaptability. (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - October 18, 2019 Category: Cancer & Oncology Source Type: research

Self-assembled small molecule natural product gel for drug delivery: a breakthrough in new application of small molecule natural products
Publication date: Available online 6 October 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Kangkang Zhi, Jiacheng Wang, Haitian Zhao, Xin YangAbstractNatural products, as a gift of nature to humanity, have long been used as drugs or pharmacological actives to help people cure various diseases. Yet we still know comparatively little about their ability to be materials. In recent years, some small molecule natural products isolated from traditional Chinese medicines have been found to have new features, namely, self-assembly to form gels (i.e., natural product gels, NPG). However, the application development of these nat...
Source: Acta Pharmaceutica Sinica B - October 8, 2019 Category: Cancer & Oncology Source Type: research

PCC0208017, a novel small-molecule inhibitor of MARK3/MARK4, suppresses glioma progression in vitro and in vivo
Publication date: Available online 18 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Fangfang Li, Zongliang Liu, Heyuan Sun, Chunmei Li, Wenyan Wang, Liang Ye, Chunhong Yan, Jingwei Tian, Hongbo WangAbstractGliomas 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. In vitro, PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferati...
Source: Acta Pharmaceutica Sinica B - October 6, 2019 Category: Cancer & Oncology Source Type: research

Protective role of berberine on ulcerative colitis through modulating enteric glial cells–intestinal epithelial cells–immune cells interactions
This study demonstrates the pathological role of functional defects of enteric glial cells (EGCs) and an infusive mechanism of therapeutic effects of berberine in ulcerative colitis. Berberine could maintain the intestinal residence of EGCs and modulate the interactions between EGCs, epithelial cells and immune cells. (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - October 5, 2019 Category: Cancer & Oncology Source Type: research

Design of Drug-like Hepsin Inhibitors against Prostate Cancer and Kidney Stones
Publication date: Available online 28 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Vincent Blay, Mu-Chun Li, Sunita P. Ho, Mashall L. Stoller, Hsing-Pang Hsieh, Douglas R. HoustonAbstractHepsin, a transmembrane serine protease abundant in renal endothelial cells, is a promising therapeutic target against several cancers, particularly prostate cancer. It is involved in the release and polymerization of uromodulin in the urine, which plays a role in kidney stone formation. In this work, we design new potential hepsin inhibitors for high activity, improved specificity towards hepsin, and promising ADMET propert...
Source: Acta Pharmaceutica Sinica B - September 29, 2019 Category: Cancer & Oncology Source Type: research

Combinatory antitumor therapy by cascade targeting of a single drug
Publication date: Available online 5 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Aiyun Liu, Huaisong Wang, Xiaoshuang Hou, Yu Ma, Gongjun Yang, Yanglong Hou, Ya DingAbstractCombination 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. Either PTX or its triphenylphosphine derivative (TPTX) is encapsulated in galac...
Source: Acta Pharmaceutica Sinica B - September 28, 2019 Category: Cancer & Oncology Source Type: research

Synthesis, in vitro and in vivo biological evaluation of novel lappaconitine derivatives as potential anti-inflammatory agents
Publication date: Available online 13 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Lei Pang, Chuan-Yan Liu, Guo-Hua Gong, Zhe-Shan QuanAbstractLappaconitine (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. In the initial screening of LA derivatives against NO production, all the target co...
Source: Acta Pharmaceutica Sinica B - September 28, 2019 Category: Cancer & Oncology Source Type: research

Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses
Publication date: Available online 25 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Xi Chen, Xiaohui Pan, Wenxin Zhang, Hongjie Guo, Shuyuan Cheng, Qiaojun He, Bo Yang, Ling DingAbstractImmunotherapy strategies targeting the programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) pathway in clinical treatments have achieved remarkable success in treating multiple types of cancer. However, owing to the heterogeneity of tumors and individual immune systems, PD-L1/PD-1 blockade still shows slow response rates in controlling malignancies in many patients. Accumulating evidence has shown that an effe...
Source: Acta Pharmaceutica Sinica B - September 26, 2019 Category: Cancer & Oncology Source Type: research

Table of Contents
Publication date: September 2019Source: Acta Pharmaceutica Sinica B, Volume 9, Issue 5Author(s): (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - September 22, 2019 Category: Cancer & Oncology Source Type: research

Anticancer drug discovery by targeting cullin neddylation
Publication date: Available online 20 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Qing Yu, Yihan Jiang, Yi SunAbstractProtein neddylation is a post-translational modification which transfers the ubiquitin-like protein NEDD8 to a lysine residue of the target substrate through a three-step enzymatic cascade. The best-known substrates of neddylation are cullin family proteins, which are the core component of Cullin-RING E3 ubiquitin ligases (CRLs). Given that cullin neddylation is required for CRL activity, and CRLs control the turn-over of a variety of key signal proteins and are often abnormally activated in...
Source: Acta Pharmaceutica Sinica B - September 22, 2019 Category: Cancer & Oncology Source Type: research

PCC0208017, a novel small-molecule inhibitor of MARK3/MARK4, suppresses glioma progression in vitro and in vivo
Publication date: Available online 18 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Fangfang Li, Zongliang Liu, Heyuan Sun, Chunmei Li, Wenyan Wang, Liang Ye, Chunhong Yan, Jingwei Tian, Hongbo WangAbstractGliomas 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. In vitro, PCC0208017 strongly inhibited kinase activity against MARK3 and MARK4, and strongly reduced proliferation in...
Source: Acta Pharmaceutica Sinica B - September 19, 2019 Category: Cancer & Oncology Source Type: research

Lineage reprogramming of fibroblasts into induced cardiac progenitor cells by CRISPR/Cas9-based transcriptional activators
Publication date: Available online 17 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Jianglin Wang, Xueyan Jiang, Lixin Zhao, Shengjia Zuo, Xiantong Chen, Lingmin Zhang, Zhongxiao Lin, Xiaoya Zhao, Yuyan Qin, Xinke Zhou, Xi-Yong YuAbstractOverexpression 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. Here ...
Source: Acta Pharmaceutica Sinica B - September 19, 2019 Category: Cancer & Oncology Source Type: research

Synthesis, in vitro and in vivo biological evaluation of novel lappaconitine derivatives as potential anti-inflammatory agents
Publication date: Available online 13 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Lei Pang, Chunyan Liu, Guohua Gong, Zheshan QuanAbstractLappaconitine (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. In the initial screening of LA derivatives against NO production, all the target compou...
Source: Acta Pharmaceutica Sinica B - September 14, 2019 Category: Cancer & Oncology Source Type: research

Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives as potent HIV-1 NNRTIs
In this report, a series of novel piperidine-substituted thiophene[3,2-d]pyrimidine derivatives were designed to explore the hydrophobic channel of the non-nucleoside reverse transcriptase inhibitors binding pocket (NNIBP) by incorporating an aromatic moiety to the left wing of the lead K-5a2. The newly synthesized compounds were evaluated for anti-HIV potency in MT-4 cells and inhibitory activity to HIV-1 reverse transcriptase (RT). Most of the synthesized compounds exhibited broad-spectrum activity toward wild-type and a wide range of HIV-1 strains carrying single non-nucleoside reverse transcriptase inhibitors (NNRTI)-r...
Source: Acta Pharmaceutica Sinica B - September 14, 2019 Category: Cancer & Oncology Source Type: research

Indole alkaloid glycosides with a 1′-(phenyl)ethyl unit from Isatis indigotica leaves
Publication date: Available online 12 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Qinglan Guo, Dawei Li, Chengbo Xu, Chenggen Zhu, Ying Guo, Haibo Yu, Xiaoliang Wang, Jiangong ShiAbstractSeven indole alkaloid glycosides containing a 1′-(4″-hydroxy-3″,5″-dimethoxyphenyl)ethyl unit (1–7) were isolated from an aqueous extract of Isatis indigotica leaves (da qing ye). Their structures were determined by spectroscopic data analysis combined with enzymatic hydrolysis as well as comparison of their experimental CD (circular dichroism) and calculated ECD (electrostatic circular dichroi...
Source: Acta Pharmaceutica Sinica B - September 14, 2019 Category: Cancer & Oncology Source Type: research

Real-time toxicity prediction of Aconitum stewing system using extractive electrospray ionization mass spectrometry
Publication date: Available online 11 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Zi-Dong Qiu, Jin-Long Chen, Wen Zeng, Ying Ma, Tong Chen, Jin-Fu Tang, Chang-Jiang-Sheng Lai, Lu-Qi HuangAbstractDue to numerous obstacles such as complex matrices, real-time monitoring of complex reaction systems (e.g., medicinal herb stewing system) has always been a challenge though great values for safe and rational use of drugs. Herein, facilitated by the potential ability on the tolerance of complex matrix of extractive electrospray ionization mass spectrometry, a device was established to realize continuous sampling and...
Source: Acta Pharmaceutica Sinica B - September 12, 2019 Category: Cancer & Oncology Source Type: research

Degradation of proteins by PROTACs and other strategies
Publication date: Available online 13 August 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Yang Wang, Xueyang Jiang, Feng Feng, Wenyuan Liu, Haopeng SunAbstractBlocking 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 clin...
Source: Acta Pharmaceutica Sinica B - September 11, 2019 Category: Cancer & Oncology Source Type: research

Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions
This study demonstrates the pathological role of functional defects of enteric glial cells (EGCs) and an infusive mechanism of therapeutic effects of berberine in ulcerative colitis. Berberine could maintain the intestinal residence of EGCs and modulate the interactions between EGCs, epithelial cells and immune cells. (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - September 6, 2019 Category: Cancer & Oncology Source Type: research

Synthesis and biological evaluation of a series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3H)-ones as potential HIV-1 inhibitors
Publication date: Available online 5 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Yumeng Wu, Chengrun Tang, Ruomei Rui, Liumeng Yang, Wei Ding, Jiangyuan Wang, Yiming Li, Christopher C. Lai, Yueping Wang, Ronghua Luo, Weilie Xiao, Hongbing Zhang, Yongtang Zheng, Yanping HeAbstractA series of 2-(((5-akly/aryl-1H-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3H)-ones were synthesized and their anti-HIV-1 activities was evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC50 values in the range of 0.0038 to 0.4759 μmol/L. Among those com...
Source: Acta Pharmaceutica Sinica B - September 6, 2019 Category: Cancer & Oncology Source Type: research

Combinatory Antitumor Therapy by a Cascade Targeting of a Single Drug
Publication date: Available online 5 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Aiyun Liu, Huaisong Wang, Xiaoshuang Hou, Yu Ma, Gongjun Yang, Yanglong Hou, Ya DingAbstractCombination 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. Either PTX or its triphenylphosphine derivative (TPTX) is encapsulated in galac...
Source: Acta Pharmaceutica Sinica B - September 5, 2019 Category: Cancer & Oncology Source Type: research

Class I histone deacetylase inhibition is synthetic lethal with BRCA1 deficiency in breast cancer cells
In this study, we found that inhibition of the class I histone deacetylases (HDAC) exhibited synthetic lethality with BRCA1 deficiency in breast cancer cells. Transcriptome profiling and validation study showed that HDAC inhibition enhanced the expression of thioredoxin interaction protein (TXNIP), causing reactive oxygen species (ROS)-mediated DNA damage. This effect induced preferential apoptosis in BRCA1–/– breast cancer cells where DNA repair system is compromised. Two animal experiments and gene expression-associated patients’ survival analysis further confirmed in vivo synthetic lethality between BR...
Source: Acta Pharmaceutica Sinica B - September 5, 2019 Category: Cancer & Oncology Source Type: research

Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease
Publication date: Available online 29 July 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Xiaokang Li, Jian Lu, Yixiang Xu, Jiaying Wang, Xiaoxia Qiu, Lei Fan, Baoli Li, Wenwen Liu, Fei Mao, Jin Zhu, Xu Shen, Jian LiAbstractDrug 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 act...
Source: Acta Pharmaceutica Sinica B - September 5, 2019 Category: Cancer & Oncology Source Type: research

Therapeutic strategies for the costimulatory molecule OX40 in T-cell mediated immunity
Publication date: Available online 3 September 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Yu Fu, Qing Lin, Zhirong Zhang, Ling ZhangAbstractThe 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. In this review we summarize the impact of the OX40–OX40L intera...
Source: Acta Pharmaceutica Sinica B - September 5, 2019 Category: Cancer & Oncology Source Type: research

Inactivation of TFEB and NF-κB by marchantin M alleviates the chemotherapy-driven pro-tumorigenic senescent secretion
In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effecst of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-κB (NF-κB) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a syner...
Source: Acta Pharmaceutica Sinica B - September 2, 2019 Category: Cancer & Oncology Source Type: research

Novel Small Molecule Retrograde Transport Blocker Confers Post-Exposure Protection against Ricin Intoxication
In this study, by structural modification of a retrograde transport blocker Retro-2cycl, a series of novel compounds were obtained. The primary screen revealed that compound 27 has an improved anti-ricin activity compare to positive control. In vitro pre-exposure evaluation in Madin–Darby Canine Kidney (MDCK) cells demonstrated that 27 is a powerful anti-ricin compound with an EC50 of 41.05 nmol/L against one LC (lethal concentration, 5.56 ng/mL) of ricin. Further studies surprisingly indicated that 27 confers post-exposure activity against ricin intoxication. An in vivo study showed that 1 h post-exposure administra...
Source: Acta Pharmaceutica Sinica B - August 24, 2019 Category: Cancer & Oncology Source Type: research

Recent progress in drug delivery
Publication date: Available online 19 August 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Chong Li, Jiancheng Wang, Yiguang Wang, Huile Gao, Gang Wei, Yongzhuo Huang, Haijun Yu, Yong Gan, Yongjun Wang, Lin Mei, Huabing Chen, Haiyan Hu, Zhiping Zhang, Yiguang JinAbstractDrug delivery systems (DDS) are defined as methods by which drugs are delivered to desired tissues, organs, cells and subcellular organs for drug release and absorption through a variety of drug carriers. Its usual purpose to improve the pharmacological activities of therapeutic drugs and to overcome problems such as limited solubility, drug aggregation...
Source: Acta Pharmaceutica Sinica B - August 19, 2019 Category: Cancer & Oncology Source Type: research

Whole-genome sequencing and analysis of the Chinese herbal plant Gelsemium elegans
Publication date: Available online 16 August 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Yisong Liu, Qi Tang, Pi Cheng, Mingfei Zhu, Hui Zhang, Jiazhe Liu, Mengting Zuo, Chongyin Huang, Changqiao Wu, Zhiliang Sun, Zhaoying LiuAbstractGelsemium elegans (G. elegans) (2n=2x=16) is genus of flowering plants belonging to the Gelsemicaeae family. Here, we report a high-quality genome assembly using the Oxford Nanopore Technologies (ONT) platform and high-throughput chromosome conformation capture techniques (Hi-C). A total of 56.11 Gb of raw GridION X5 platform ONT reads (6.23 Gb per cell) were generated. After filtering, ...
Source: Acta Pharmaceutica Sinica B - August 17, 2019 Category: Cancer & Oncology Source Type: research

Degradation of protein by PROTAC and other strategies
Publication date: Available online 13 August 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Yang Wang, Xueyang Jiang, Feng Feng, Wenyuan Liu, Haopeng SunAbstractAbnormal protein expression or activities are associated with many diseases, especially cancer. Therefore, down-regulating the proteins involved in cancer cell survival proved to be an effective strategy for cancer treatment—a number of drugs based on proteolysis-targeting chimaera (PROTAC) mechanism have demonstrated clinical efficacy. Recent progress in the PROTAC strategy includes identification of the structure of the first ternary eutectic complex, ex...
Source: Acta Pharmaceutica Sinica B - August 15, 2019 Category: Cancer & Oncology Source Type: research

Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent
Publication date: Available online 14 August 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Hongxuan Feng, Linghao Hu, Hongwen Zhu, Lingxue Tao, Lei Wu, Qinyuan Zhao, Yemi Gao, Qi Gong, Fei Mao, Xiaokang Li, Hu Zhou, Jian Li, Haiyan ZhangAbstractIschemic 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 neur...
Source: Acta Pharmaceutica Sinica B - August 15, 2019 Category: Cancer & Oncology Source Type: research

Nobiletin and its derivatives overcome multidrug resistance (MDR) in cancer: Total synthesis and discovery of potent MDR reversal agents
Publication date: Available online 31 July 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Senling Feng, Huifang Zhou, Deyan Wu, Dechong Zheng, Biao Qu, Ruiming Liu, Chen Zhang, Zhe Li, Ying Xie, Hai-Bin LuoAbstractOur 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 in vitro. However, its low aqueous solubility and difficulty in the total synthesis limit its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six st...
Source: Acta Pharmaceutica Sinica B - August 2, 2019 Category: Cancer & Oncology Source Type: research

Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease
Publication date: Available online 29 July 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Xiaokang Li, Jian Lu, Yixiang Xu, Jiaying Wang, Xiaoxia Qiu, Lei Fan, Baoli Li, Wenwen Liu, Fei Mao, Jin Zhu, Xu Shen, Jian LiAbstractDrug 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 act...
Source: Acta Pharmaceutica Sinica B - July 30, 2019 Category: Cancer & Oncology Source Type: research

Regulation of microbiota–GLP1 axis by sennoside A in diet-induced obese mice
In this study, the impact of SA on insulin sensitivity was tested in high fat diet (HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR (homeostatic model assessment for insulin resistance) and glucose tolerance test (GTT). SA restored plasma level of glucagon-like peptide 1 (GLP1) by 90% and mRNA expression of Glp1 by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids (SCFAs), and mucosal structure in the colon. A mitochondrial...
Source: Acta Pharmaceutica Sinica B - July 27, 2019 Category: Cancer & Oncology Source Type: research

Reimaging biological barriers affecting distribution and extravasation of PEG/peptide- modified liposomes in xenograft SMMC7721 tumor
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. Type I collagen fibers and macrophage ...
Source: Acta Pharmaceutica Sinica B - July 27, 2019 Category: Cancer & Oncology Source Type: research

Regulation of expression of drug-metabolizing enzymes by oncogenic signaling pathways in liver tumors: a review
Publication date: Available online 26 July 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Albert Braeuning, Michael SchwarzAbstractMutations in genes encoding key players in oncogenic signaling pathways trigger specific downstream gene expression profiles in the respective tumor cell populations. While regulation of genes related to cell growth, survival, and death has been extensively studied, much less is known on the regulation of drug-metabolizing enzymes (DMEs) by oncogenic signaling. Here, a comprehensive review of the available literature is presented summarizing the impact of the most relevant genetic alteration...
Source: Acta Pharmaceutica Sinica B - July 27, 2019 Category: Cancer & Oncology Source Type: research

Disturbed Yin–Yang balance: stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1
Publication date: Available online 22 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Chang Yan, Zhuo Luo, Wen Li, Xue Li, Robert Dallmann, Hiroshi Kurihara, Yi-Fang Li, Rong-Rong HeAbstractHerpes 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 via 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...
Source: Acta Pharmaceutica Sinica B - July 26, 2019 Category: Cancer & Oncology Source Type: research

A one-step specific assay for continuous detection of sirtuin 2 activity
In this study, we designed a series of fluorescent nonapeptide probes derived from substrates of SIRT1–SIRT3. Fluorescence increment of these probes is based on SIRT-mediated removal of the acyl side chain with fluorophore, which makes this system free of lysine-recognizing protease. Comparing the reaction of these fluorescent nonapeptide substrates with SIRT1–SIRT3 and SIRT6, it was confirmed that this assessment system was the most suitable for SIRT2 activity detection. Thus, SIRT2 was used to modify substrates by truncating the amino acids or lysine side chain of nonapeptide. Finally, two specific and effici...
Source: Acta Pharmaceutica Sinica B - July 24, 2019 Category: Cancer & Oncology Source Type: research

Table of Contents
Publication date: July 2019Source: Acta Pharmaceutica Sinica B, Volume 9, Issue 4Author(s): (Source: Acta Pharmaceutica Sinica B)
Source: Acta Pharmaceutica Sinica B - July 24, 2019 Category: Cancer & Oncology Source Type: research

De novo biosynthesis of liquiritin in Saccharomyces cerevisiae
Publication date: Available online 23 July 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Yan Yin, Yanpeng Li, Dan Jiang, Xianan Zhang, Wei Gao, Chunsheng LiuAbstractLiquiritigenin (LG), isoliquiritigenin (Iso-LG), together with their respective glycoside derivatives liquiritin (LN) and isoliquiritin (Iso-LN), are the main active flavonoids of Glycyrrhiza uralensis, 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 medici...
Source: Acta Pharmaceutica Sinica B - July 24, 2019 Category: Cancer & Oncology Source Type: research

Cdk5 knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity
Publication date: Available online 23 July 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Huan Deng, Songwei Tan, Xueqin Gao, Chenming Zou, Chenfeng Xu, Kun Tu, Qingle Song, Fengjuan Fan, Wei Huang, Zhiping ZhangAbstractBlocking 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 co...
Source: Acta Pharmaceutica Sinica B - July 24, 2019 Category: Cancer & Oncology Source Type: research

Targeted delivery of hyaluronic acid nanomicelles to hepatic stellate cells in hepatic fibrosis rats
Publication date: Available online 18 July 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Wenhao Li, Chuchu Zhou, Yao Fu, Tijia Chen, Xing Liu, Zhirong Zhang, Tao GongAbstractHepatic 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. We found that when hepatic fibrosis occurs, the expression of CD44 receptors on the surface of HSCs is significantly increased. Based on...
Source: Acta Pharmaceutica Sinica B - July 19, 2019 Category: Cancer & Oncology Source Type: research

Novel radioligands for imaging sigma-1 receptor in brain using positron emission tomography (PET)
Publication date: Available online 11 July 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Yu Lan, Ping Bai, Zude Chen, Ramesh Neelamegam, Michael S. Placzek, Hao Wang, Stephanie A. Fiedler, Jing Yang, Gengyang Yuan, Xiying Qu, Hayden R. Schmidt, Jinchun Song, Marc D. Normandin, Chongzhao Ran, Changning WangAbstractThe sigma-1 receptor (σ1R) is a unique intracellular protein. σ1R plays a major role in various pathological conditions in the central nervous system (CNS), implicated in several neuropsychiatric disorders. Imaging of σ1R in the brain using positron emission tomography (PET) could serve as a ...
Source: Acta Pharmaceutica Sinica B - July 13, 2019 Category: Cancer & Oncology Source Type: research

Targeting peptide-decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor
Publication date: Available online 5 June 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Tao Tan, Yuqi Wang, Jing Wang, Zhiwan Wang, Hong Wang, Haiqiang Cao, Jie Li, Yaping Li, Zhiwen Zhang, Siling WangAbstractThe 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...
Source: Acta Pharmaceutica Sinica B - July 11, 2019 Category: Cancer & Oncology Source Type: research

Probiotics modulate the microbiota–gut–brain axis and improve memory deficits in aged SAMP8 mice
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. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood–brain barrier...
Source: Acta Pharmaceutica Sinica B - July 8, 2019 Category: Cancer & Oncology Source Type: research

Reimaging biological barriers affecting distribution and extravasation of PEG/peptide modified liposomes into xenograft SMMC7721 tumor
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. Type I collagen fibers and macrophage ...
Source: Acta Pharmaceutica Sinica B - July 3, 2019 Category: Cancer & Oncology Source Type: research