Abstract：
:Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels. Nevertheless, some problems and challenges remain. In this review we first describes the structure and function of PCSK9 and its gene polymorphisms. We then discuss the various designs of pharmacological targets of PCSK9, including those that block the binding of PCSK9 to hepatic LDLRs (mimetic peptides, adnectins, and monoclonal antibodies), inhibit PCSK9 expression (the clustered regularly interspaced short palindromic repeats/Cas9 platform, small molecules, antisense oligonucleotides, and small interfering RNAs), and interfere with PCSK9 secretion. Finally, this review highlights future challenges in this field, including safety concerns associated with PCSK9 monoclonal antibodies, the limited utility of PCSK9 inhibitors in the central nervous system, and the cost-effectiveness of PCSK9 inhibitors.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
He NY,Li Q,Wu CY,Ren Z,Gao Y,Pan LH,Wang MM,Wen HY,Jiang ZS,Tang ZH,Liu LSdoi
10.1038/aps.2016.134subject
Has Abstractpub_date
2017-03-01 00:00:00pages
301-311issue
3eissn
1671-4083issn
1745-7254pii
aps2016134journal_volume
38pub_type
杂志文章,评审abstract：:Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the world. Although considerable progress has been made in the diagnosis, treatment and prognosis of CVD, there is still a critical need for novel diagnostic biomarkers and new therapeutic interventions to decrease the incidence of this ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2018.30
更新日期：2018-07-01 00:00:00
abstract：AIM:To study wound healing activity of the human placental extract (HPE) in rats. METHODS:Full thickness wounds were inflicted on depilated dorsum of Charles foster rats with 8 mm Acu-punch biopsy. The HPE was applied both at topical and im routes (2.5 mL/kg). Effects were compared on the basis of physical criteria, b...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2001-12-01 00:00:00
abstract：AIM:To evaluate the efficiency of 3 short hairpin RNA (shRNA) interfering with the herpes simplex virus type 1 (HSV-1) gene coding glycoprotein D (gD) for inhibiting the gD expression and virus replication in vitro. METHODS:Vero cells were selected for an in vitro model of infection. Three shRNA sequences (shRNAgD1, -...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00828.x
更新日期：2008-08-01 00:00:00
abstract：AIM:To investigate the effect of a group of novel synthetic dithiolane analogs of lignans and a well characterized platelet-activating factor (PAF) receptor antagonist, L659,989 on PAF-receptor binding, IFN-gamma- and lipopolysaccharide (LPS)-induced NO production, and steady-state inducible nitric-oxide synthase (iNOS...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
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更新日期：2000-10-01 00:00:00
abstract：AIM:To investigate effects of CpG oligodeoxynucleotide (CpG ODN) on the mRNA expression of transcription factors GATA binding protein 3 (GATA-3) and T-box expressed in T cells (T-bet) in asthmatic mice. METHODS:An asthmatic mouse model was established and treated with CpG ODN. Total inflammatory cells and eosinophils ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00157.x
更新日期：2005-09-01 00:00:00
abstract：AIM:To study the changes of phospholipase D (PLD) activity of actively sensitized rat peritoneal mast cells (RPMC) in degranulation. METHODS:Degranulation of RPMC was determined by measurement of beta-hexosaminidase release. PLD activity assay was carried out by measurement of PLD product, choline, with chemiluminesce...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
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abstract：AIM:The aim of this study was to study the effects of compound FLZ, a novel cyclic derivative of squamosamide from Annona glabra, on brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element-binding protein (CREB) signaling and neuronal apoptosis in the hippocampus of the amylo...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.3
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abstract：AIM:To explore correlation of T helper 1 (Th1) and Th2 cytokine between the cortical layer and pulmonary airway in ovalbumin-induced rat asthma model. METHODS:Aerosol antigen-induced changes of inflammation in bronchoalveolar lavage fluids (BALF) and pulmonary histologic section in sensitized rats were investigated. C...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
abstract：AIM:Ischemia/reperfusion is an initial triggering event that leads to gut-induced acute lung injury (ALI). In this study, we investigated whether hypoxia inducible factor-1α (HIF-1α) played a role in the pathogenesis of lung injury induced by trauma and hemorrhagic shock (T/HS). METHODS:Male Wistar rats underwent lapa...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.5
更新日期：2012-05-01 00:00:00
abstract：AIM:It is generally assumed that only unbound drugs can reach the site of action by diffusing across the membranes and exerting pharmacological effects by interacting with receptors. Recent research has shown that the percentage of free drugs may depend on the total drug concentration. The aim of the paper is to verify...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2006.00454.x
更新日期：2006-12-01 00:00:00
abstract：AIM:To develop a robust, cell-based, high-content screening (HCS) assay based on receptor internalization for the identification of novel modulators of the epidermal growth factor receptor (EGFR). METHODS:Agonist-induced receptor internalization is part of the signaling cascade of EGFR. Fluorescent-tagged epidermal gr...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00640.x
更新日期：2007-10-01 00:00:00
abstract：AIM:To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers. METHODS:This was an open-label, single- and multiple-dose study. The subjects were assigned to receive a single dose, 675, 2025, or 4050 mg, of calcium L-threonate (n=...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.138
更新日期：2011-12-01 00:00:00
abstract：AIM:To investigate the signaling pathways involved in thrombin-induced connective tissue growth factor (CTGF) expression in rat vascular smooth muscle cells (VSMCs). METHODS:Experiments were preformed on primary rat aortic smooth muscle cells (RASMCs) and a rat VSMC line (A10). CTGF protein levels were measured using ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.178
更新日期：2012-01-01 00:00:00
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journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:Volatile anesthetics improve postischemic cardiac function and reduce infarction even when administered for only a brief time at the onset of reperfusion. A recent study showed that sevoflurane postconditioning (SPC) attenuated myocardial reperfusion injury, but the underlying mechanisms remain unclear. In this study,...
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pub_type： 杂志文章
doi：10.1038/s41401-018-0066-y
更新日期：2019-01-01 00:00:00
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journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-05-01 00:00:00
abstract：AIM:To investigate the stereoselective metabolism of propafenone (PPF) by human liver CYP3A4. METHODS:A chiral and an achiral HPLC were combined to determine the enantiomer of PPF in S9 incubates prepared from transgenic Chinese hamster CHL cells lines expressing CYP3A4. The time-dependent study was performed using in...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:The fibroblast growth factor receptors (FGFRs) are increasingly considered attractive targets for therapeutic cancer intervention due to their roles in tumor metastasis and angiogenesis. Here, we identified a new selective FGFR inhibitor, C11, and assessed its antitumor activities. C11 was a selective FGFR1 inhibitor ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0191-7
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journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.23
更新日期：2010-04-01 00:00:00
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pub_type： 杂志文章
doi：
更新日期：2004-02-01 00:00:00
abstract：AIM:To investigate whether geniposide, an iridoid glucoside extracted from gardenia jasminoides ellis fruits, inhibits cell adhesion to human umbilical vein endothelial cells (HUVECs) induced by high glucose and its underlying mechanisms. METHODS:HUVECs were isolated from human umbilical cords and cultured. The adhesi...
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pub_type： 杂志文章
doi：10.1038/aps.2010.83
更新日期：2010-08-01 00:00:00
abstract：:Immune checkpoint blockade therapy has become a first-line treatment in various cancers. But there are only a small percent of colorectal patients responding to PD-1/PD-L1 blockage immunotherapy. How to increase their treatment efficacy is an urgent and clinically unmet need. It is acknowledged that immunogenic cell d...
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pub_type： 杂志文章
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更新日期：2020-12-11 00:00:00
abstract：AIM:To evaluate the pharmacokinetic characteristics of L-valyl-ara-C, a peptidomimetic prodrug of ara-C. METHODS:After the synthesis of L-valyl-ara-C, the in vitro stability of L-valyl-ara-C was examined in various biological media. Plasma pharmacokinetic profiles of ara-C and L-valyl-ara-C were also evaluated in rats...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00474.x
更新日期：2007-02-01 00:00:00
abstract：:Type 2 diabetes (T2D) and Alzheimer's disease (AD) share several common pathophysiological features. Huperzine A (Hup A), a Lycopodium alkaloid extracted from the Chinese herb moss Huperzia serrata, is a specific and reversible inhibitor of acetylcholinesterase, which is clinically used for the treatment of AD. In thi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0257-1
更新日期：2020-02-01 00:00:00
abstract：AIM:Our previous study demonstrated an siRNA-mediated, allele-specific silencing of mutant genes that cause amyotrophic lateral sclerosis. To improve siRNA design for better therapeutic use of RNA interference, we systematically tested the base-pairing mismatch strategy in the design of asymmetric siRNA. METHODS:A nat...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00740.x
更新日期：2008-02-01 00:00:00
abstract：AIM:To investigate the influences of betulinic acid (BA), a triterpenoid isolated from birch bark, on neuroinflammatory mediators involved in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis in vitro. METHODS:Encephalitogenic T cells were prepared from draining lymph nodes and spina...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.181
更新日期：2013-03-01 00:00:00
abstract：:Recent evidence shows that high glucose levels recruit carbohydrate response element-binding protein, which binds the promoter of thioredoxin-interacting protein (txnip), thereby regulating its expression in β-cells. Overexpression of txnip not only induces β-cell apoptosis but also reduces insulin production. Thus, t...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2017.15
更新日期：2017-07-01 00:00:00
abstract：AIM:To investigate the blocking effects of methylflavonolamine (MFA) on human Na(V)1.5 channels expressed in Xenopus laevis oocytes and on sodium currents (I(Na)) in rabbit ventricular myocytes. METHODS:Human Na(V)1.5 channels were expressed in Xenopus oocytes and studied using the two-electrode voltage-clamp techniqu...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.8
更新日期：2010-03-01 00:00:00
abstract：AIM:Chinese medicine CGA formula consists of polysaccharide from Cordyceps sinensis mycelia (CS-PS), gypenosides and amygdalin, which is derived from Fuzheng Huayu (FZHY) capsule for treating liver fibrosis. In this study we attempted to confirm the therapeutic effects of CGA formula in dimethylnitrosamine (DMN)-induce...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2016.35
更新日期：2016-06-01 00:00:00
abstract：AIM:To model the three-dimensional structure and investigate the interaction mechanism of the proprotein convertase furin/kexin and their inhibitors (eglin c mutants). METHODS:The three-dimensional complex structures of furin/kexin with its inhibitors, eglin c mutants, were generated by modeller program using the newl...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-12-01 00:00:00
