587 results match your criteria Acta Pharmaceutica Sinica B[Journal]


Erratum: Author correction to 'Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer' [Acta Pharmaceutica Sinica B 2019; 9(5):1061-1077].

Acta Pharm Sin B 2020 Jun 26;10(6):1143-1144. Epub 2020 Mar 26.

Key Laboratory of Molecular Pharmaceutics, New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

[This corrects the article DOI: 10.1016/j.apsb. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332668PMC

Design and synthesis of selective sphingosine-1-phosphate receptor 1 agonists with increased phosphorylation rates.

Acta Pharm Sin B 2020 Jun 15;10(6):1134-1142. Epub 2019 Nov 15.

Department of Medicinal Chemistry, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100050, China.

FTY720 and IMMH002, prodrugs for sphingosine-1-phosphate receptor 1 (S1P) agonists, show inadequate and inconsistent levels of phosphorylation in humans compared to that in rats. In this study, FTY720 or IMMH002 analogues (-) were designed and synthesized with modified head pieces to improve the biotransformation of the prodrugs to the active phosphorylated forms. Target compounds were synthesized a convergent route using the key and optically pure building block , which was first synthesized asymmetrically catalyzed amination. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332640PMC

Interfacial properties and micellization of triblock poly(ethylene glycol)-poly(-caprolactone)-polyethyleneimine copolymers.

Acta Pharm Sin B 2020 Jun 20;10(6):1122-1133. Epub 2020 Jan 20.

Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

This study aimed to explore the link between block copolymers' interfacial properties and nanoscale carrier formation and found out the influence of length ratio on these characters to optimize drug delivery system. A library of diblock copolymers of PEG-PCL and triblock copolymers with additional PEI (PEG-PCL-PEI) were synthesized. Subsequently, a systematic isothermal investigation was performed to explore molecular arrangements of copolymers at air/water interface. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332608PMC

Platinum complexes of curcumin delivered by dual-responsive polymeric nanoparticles improve chemotherapeutic efficacy based on the enhanced anti-metastasis activity and reduce side effects.

Acta Pharm Sin B 2020 Jun 1;10(6):1106-1121. Epub 2019 Nov 1.

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

Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum-curcumin complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt-CUR@PSPPN) to facilitate intracellular release and synergistic anti-cancer effects. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332658PMC

The construction of nasal cavity-mimic M-cell model, design of M cell-targeting nanoparticles and evaluation of mucosal vaccination by nasal administration.

Acta Pharm Sin B 2020 Jun 4;10(6):1094-1105. Epub 2020 Mar 4.

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.

In order to better evaluate the transport effect of nanoparticles through the nasal mucosa, an nasal cavity-mimic model was designed based on M cells. The differentiation of M cells was induced by co-culture of Calu-3 and Raji cells in invert model. The ZO-1 protein staining and the transport of fluorescein sodium and dexamethasone showed that the inverted co-culture model formed a dense monolayer and possessed the transport ability. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332807PMC

metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging.

Acta Pharm Sin B 2020 Jun 11;10(6):1083-1093. Epub 2019 Dec 11.

Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China.

Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development. Herein, an metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was established for direct analysis of metabolites in renal tissue sections. This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I, a known nephrotoxic drug, aimed to discover metabolites associated with nephrotoxicity. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332651PMC

Antinociceptive grayanane-derived diterpenoids from flowers of .

Acta Pharm Sin B 2020 Jun 6;10(6):1073-1082. Epub 2019 Nov 6.

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.

Twelve new grayanoids (-) along with five known compounds were isolated from flowers of . Their structures were fully characterized using a combination of spectroscopic analyses, computational calculations, and single crystal X-ray diffraction. Rhomollone A () possesses an unprecedented 5/6/6/5 tetra-cyclic ring system (B- grayanane) incorporating a cyclopentene-1,3-dione scaffold. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332786PMC

Arsenic trioxide induces regulatory functions of plasmacytoid dendritic cells through interferon- inhibition.

Acta Pharm Sin B 2020 Jun 31;10(6):1061-1072. Epub 2020 Jan 31.

Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Paris F-75012, France.

Arsenic trioxide (AsO) is recently found to have therapeutic potential in systemic sclerosis (SSc), a life-threatening multi-system fibrosing autoimmune disease with type I interferon (IFN-I) signature. Chronically activated plasmacytoid dendritic cells (pDCs) are responsible for IFN-I secretion and are closely related with fibrosis establishment in SSc. In this study, we showed that high concentrations of AsO induced apoptosis of pDCs mitochondrial pathway with increased BAX/BCL-2 ratio, while independent of reactive oxygen species generation. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.01.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332672PMC

A novel cyclic peptide targeting LAG-3 for cancer immunotherapy by activating antigen-specific CD8 T cell responses.

Acta Pharm Sin B 2020 Jun 13;10(6):1047-1060. Epub 2020 Jan 13.

School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.

PD-1 and CTLA-4 antibodies offer great hope for cancer immunotherapy. However, many patients are incapable of responding to PD-1 and CTLA-4 blockade and show low response rates due to insufficient immune activation. The combination of checkpoint blockers has been proposed to increase the response rates. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332792PMC

MiR-142-3p enhances chemosensitivity of breast cancer cells and inhibits autophagy by targeting HMGB1.

Acta Pharm Sin B 2020 Jun 16;10(6):1036-1046. Epub 2019 Nov 16.

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.

MiR-142-3p has been reported to act as a tumor suppressor in breast cancer. However, the regulatory effect of miR-142-3p on drug resistance of breast cancer cells and its underlying mechanism remain unknown. Here, we found that miR-142-3p was significantly downregulated in the doxorubicin (DOX)-resistant MCF-7 cell line (MCF-7/DOX). Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332808PMC

20()-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network multiomic analysis.

Acta Pharm Sin B 2020 Jun 5;10(6):1020-1035. Epub 2020 Feb 5.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China.

Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways, it is still unclear how certain drugs influence these P53 signaling networks. Here, we used a comprehensive single-cell multiomics view of the effects of ginsenosides on cancer cells. Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely associated with P53 protein. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.01.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332671PMC

RICTOR/mTORC2 affects tumorigenesis and therapeutic efficacy of mTOR inhibitors in esophageal squamous cell carcinoma.

Acta Pharm Sin B 2020 Jun 26;10(6):1004-1019. Epub 2020 Jan 26.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Dysregulation of mTORC1/mTORC2 pathway is observed in many cancers and mTORC1 inhibitors have been used clinically in many tumor types; however, the mechanism of mTORC2 in tumorigenesis is still obscure. Here, we mainly explored the potential role of mTORC2 in esophageal squamous cell carcinoma (ESCC) and its effects on the sensitivity of cells to mTOR inhibitors. We demonstrated that RICTOR, the key factor of mTORC2, and p-AKT (Ser473) were excessively activated in ESCC and their overexpression is related to lymph node metastasis and the tumor-node-metastasis (TNM) phase of ESCC patients. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332809PMC

TIMP1 preserves the blood-brain barrier through interacting with CD63/integrin 1 complex and regulating downstream FAK/RhoA signaling.

Acta Pharm Sin B 2020 Jun 5;10(6):987-1003. Epub 2020 Mar 5.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Blood-brain barrier (BBB) breakdown and the associated microvascular hyperpermeability are hallmark features of several neurological disorders, including traumatic brain injury (TBI). However, there is no viable therapeutic strategy to rescue BBB function. Tissue inhibitor of metalloproteinase-1 (TIMP1) has been considered to be beneficial for vascular integrity, but the molecular mechanisms underlying the functions of TIMP1 remain elusive. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.02.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332810PMC

Delivery strategies for macromolecular drugs in cancer therapy.

Authors:
Qin Guo Chen Jiang

Acta Pharm Sin B 2020 Jun 26;10(6):979-986. Epub 2020 Jan 26.

Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Medical Neurobiology, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.

With the development of biotherapy, biomacromolecular drugs have gained tremendous attention recently, especially in drug development field due to the sophisticated functions . Over the past few years, a motley variety of drug delivery strategies have been developed for biomacromolecular drugs to overcome the difficulties in the druggability, ., the instability and easily restricted by physiologic barriers. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332661PMC

Development of non-nucleoside reverse transcriptase inhibitors (NNRTIs): our past twenty years.

Acta Pharm Sin B 2020 Jun 21;10(6):961-978. Epub 2019 Nov 21.

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

Human immunodeficiency virus (HIV) is the primary infectious agent of acquired immunodeficiency syndrome (AIDS), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are the cornerstone of HIV treatment. In the last 20 years, our medicinal chemistry group has made great strides in developing several distinct novel NNRTIs, including 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), thio-dihydro-alkoxy-benzyl-oxopyrimidine (-DABO), diaryltriazine (DATA), diarylpyrimidine (DAPY) analogues, and their hybrid derivatives. Application of integrated modern medicinal strategies, including structure-based drug design, fragment-based optimization, scaffold/fragment hopping, molecular/fragment hybridization, and bioisosterism, led to the development of several highly potent analogues for further evaluations. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332669PMC

Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer.

Acta Pharm Sin B 2020 Jun 19;10(6):947-960. Epub 2019 Dec 19.

Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332664PMC

Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system: the relationship of hydrogen bonding strength and controlled release capacity.

Acta Pharm Sin B 2020 May 29;10(5):928-945. Epub 2019 Nov 29.

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

Background: Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch. However, the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported, and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive (PSA) was not well understood. The present study shed light on this relationship. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280149PMC

Self-assembled small molecule natural product gel for drug delivery: a breakthrough in new application of small molecule natural products.

Acta Pharm Sin B 2020 May 6;10(5):913-927. Epub 2019 Oct 6.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150000, China.

Natural 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 (. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280148PMC

Real-time toxicity prediction of stewing system using extractive electrospray ionization mass spectrometry.

Acta Pharm Sin B 2020 May 11;10(5):903-912. Epub 2019 Sep 11.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.

Due to numerous obstacles such as complex matrices, real-time monitoring of complex reaction systems (, 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 matrices of extractive electrospray ionization mass spectrometry, a device was established to realize continuous sampling and real-time quantitative analysis of herb stewing system for the first time. A complete analytical strategy, including data acquisition, data mining, and data evaluation was proposed and implemented with overcoming the usual difficulties in real-time mass spectrometry quantification. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276682PMC

Indole alkaloid glycosides with a 1'-(phenyl)ethyl unit from leaves.

Acta Pharm Sin B 2020 May 12;10(5):895-902. Epub 2019 Sep 12.

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

Seven indole alkaloid glycosides containing a 1'-(4″-hydroxy-3″,5″-dimethoxyphenyl)ethyl unit (-) were isolated from an aqueous extract of 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 dichroism) spectra. Based on analysis of and/or Cotton effect (CE) data of -, two simple roles to assign location and/or configuration of -glycopyranosyloxy and 1'-(phenyl)ethyl units in the indole alkaloid glycosides are proposed. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280145PMC

Exploring the hydrophobic channel of NNIBP leads to the discovery of novel piperidine-substituted thiophene[3,2-]pyrimidine derivatives as potent HIV-1 NNRTIs.

Acta Pharm Sin B 2020 May 14;10(5):878-894. Epub 2019 Sep 14.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.

In this report, a series of novel piperidine-substituted thiophene[3,2-]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 . 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)-resistant mutations. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280082PMC

A new perspective of triptolide-associated hepatotoxicity: the relevance of NF- B and NF- B-mediated cellular FLICE-inhibitory protein.

Acta Pharm Sin B 2020 May 28;10(5):861-877. Epub 2020 Feb 28.

Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280150PMC

Characterization of organic anion transporting polypeptide 1b2 knockout rats generated by CRISPR/Cas9: a novel model for drug transport and hyperbilirubinemia disease.

Acta Pharm Sin B 2020 May 14;10(5):850-860. Epub 2019 Nov 14.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Organic anion transporting polypeptide 1B1 and 1B3 (OATP1B1/3) as important uptake transporters play a fundamental role in the transportation of exogenous drugs and endogenous substances into cells. Rat OATP1B2, encoded by the gene, is homologous to human OATP1B1/3. Although OATP1B1/3 is very important, few animal models can be used to study its properties. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276679PMC

Interleukin-27 decreases ghrelin production through signal transducer and activator of transcription 3-mechanistic target of rapamycin signaling.

Acta Pharm Sin B 2020 May 7;10(5):837-849. Epub 2020 Jan 7.

Department of Physiology, School of Medicine, Jinan University, Guangzhou 510632, China.

Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The relationship between IL-27 and ghrelin is still unexplored. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.12.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280146PMC

NF- B/HDAC1/SREBP1c pathway mediates the inflammation signal in progression of hepatic steatosis.

Acta Pharm Sin B 2020 May 21;10(5):825-836. Epub 2020 Feb 21.

Shanghai Diabetes Institute, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.

The transcription factor nuclear factor kappa B (NF-B) is activated in hepatocytes in the pathogenesis of hepatic steatosis. However, the action mechanism of NF-B remains to be established in the hepatic steatosis. In this study, the subunit of NF-B was found to promote the hepatic steatosis through regulation of histone deacetylase 1 (HDAC1) in hepatocytes. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276689PMC

Berberine prevents primary peritoneal adhesion and adhesion reformation by directly inhibiting TIMP-1.

Acta Pharm Sin B 2020 May 19;10(5):812-824. Epub 2020 Feb 19.

Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China.

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276697PMC

Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells and o.

Acta Pharm Sin B 2020 May 26;10(5):799-811. Epub 2020 Jan 26.

State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280144PMC

Identification of the dietary supplement capsaicin as an inhibitor of Lassa virus entry.

Acta Pharm Sin B 2020 May 5;10(5):789-798. Epub 2020 Mar 5.

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

The limited treatment options for the increasing occurrence of Lassa hemorrhagic fever in West Africa poses an urgent need for the discovery and development of novel therapeutics. Dietary supplements, especially natural products that are edible and safe for human use, are a good source of drug discovery with potential for uncovering novel applications. In this study, we tested 40 natural products of dietary supplements and identified capsaicin, a common dietary supplement abundant in chili peppers, as an inhibitor of Lassa virus (LASV) entry with EC of 6. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276894PMC

Anticancer drug discovery by targeting cullin neddylation.

Acta Pharm Sin B 2020 May 20;10(5):746-765. Epub 2019 Sep 20.

Cancer Institute of the 2nd Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310029, China.

Protein 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 cancers, targeting neddylation becomes a promising approach for discovery of novel anti-cancer therapeutics. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276695PMC

Natural products, PGC-1 , and Duchenne muscular dystrophy.

Acta Pharm Sin B 2020 May 8;10(5):734-745. Epub 2020 Jan 8.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 5613156491, Iran.

Peroxisome proliferator-activated receptor (PPAR) is a transcriptional coactivator that binds to a diverse range of transcription factors. PPAR coactivator 1 (PGC-1) coactivators possess an extensive range of biological effects in different tissues, and play a key part in the regulation of the oxidative metabolism, consequently modulating the production of reactive oxygen species, autophagy, and mitochondrial biogenesis. Owing to these findings, a large body of studies, aiming to establish the role of PGC-1 in the neuromuscular system, has shown that PGC-1 could be a promising target for therapies targeting neuromuscular diseases. Read More

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http://dx.doi.org/10.1016/j.apsb.2020.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276681PMC

Epigenetic strategies synergize with PD-L1/PD-1 targeted cancer immunotherapies to enhance antitumor responses.

Acta Pharm Sin B 2020 May 25;10(5):723-733. Epub 2019 Sep 25.

Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Immunotherapy 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 effective response to anti-PD-L1/anti-PD-1 therapy requires establishing an integrated immune cycle. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276686PMC

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