Abstract：
:The chemokine receptor CCR5 is an important anti-HIV (human immunodeficiency virus) drug target owning to its pivotal role in HIV-1 viral entry as a co-receptor. Here, we present a 2.9 Å resolution crystal structure of CCR5 bound to PF-232798, a second-generation oral CCR5 antagonist currently in phase II clinical trials. PF-232798 and the marketed HIV drug maraviroc share a similar tropane scaffold with different amino (N)- and carboxyl (C)- substituents. Comparison of the CCR5-PF-232798 structure with the previously determined structure of CCR5 in complex with maraviroc reveals different binding modes of the two allosteric antagonists and subsequent conformational changes of the receptor. Our results not only offer insights into the phenomenon that PF-232798 has higher affinity and alternative resistance profile to maraviroc, but also will facilitate the design of new anti-HIV drugs.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Zhu Y,Zhao YL,Li J,Liu H,Zhao Q,Wu BL,Yang ZLdoi
10.1038/s41401-018-0054-2subject
Has Abstractpub_date
2019-04-01 00:00:00pages
563-568issue
4eissn
1671-4083issn
1745-7254pii
10.1038/s41401-018-0054-2journal_volume
40pub_type
杂志文章abstract：:Abnormal growth of the intimal layer of blood vessels (neointima formation) contributes to the progression of atherosclerosis and in-stent restenosis. Recent evidence shows that the 18-kDa translocator protein (TSPO), a mitochondrial membrane protein, is involved in diverse cardiovascular diseases. In this study we in...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-019-0293-x
更新日期：2020-01-01 00:00:00
abstract：:Human ether-a-go-go related gene (hERG) potassium (K(+)) channels play a critical role in cardiac action potential repolarization. Mutations that reduce hERG conductance or surface expression may cause congenital long QT syndrome (LQTS). However, the channels can be inhibited by structurally diverse small molecules, r...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2011.70
更新日期：2011-06-01 00:00:00
abstract：AIM:To examine whether selective serotonin reuptake inhibitor citalopram interacts with Kv1.5, one of the cardiovascular-specific Kv channel isoforms. METHODS:The interaction between citalopram and Kv1.5 expressed in Chinese hamster ovary cells was studied using the whole-cell patch-clamp technique. RESULTS:Citalopra...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2010.14
更新日期：2010-04-01 00:00:00
abstract：AIM:To study the protective effect of the polypeptide isolated from Chlamys farreri (PCF) on hairless mice skin damaged by ultraviolet A. METHODS:Enzymes and malondialdehyde (MDA) were determined by biochemical methods; the expressions of Bcl-2 protein and NOS protein were examined by immunohistochemical technique. Th...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-09-01 00:00:00
abstract：AIM:To investigate the effect of incorporation of an isoleucine zipper (IZ) motif into CD40 on binding activity of CD40 for the CD40 ligand (CD40L). METHODS:Prokaryotic expression vectors for 2 soluble CD40 derivatives, shCD40His and shCD40IZ containing an IZ domain, were constructed and expressed in Escherichia coli....
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2006.00285.x
更新日期：2006-03-01 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
doi：
更新日期：2000-10-01 00:00:00
abstract：:Cerebral ischemia/reperfusion (I/R) results in harmful consequences during ischemic stroke, especially the disruption of the blood-brain barrier (BBB), which leads to severe hemorrhagic transformation through aggravation of edema and brain hemorrhage. Our previous study demonstrated that icariside II (ICS II), which i...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-020-0409-3
更新日期：2020-12-01 00:00:00
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
更新日期：2010-03-01 00:00:00
abstract：:Diabetic retinopathy (DR) is a common complication of diabetes and has been recognized as the leading cause of blindness in adults. Several interrelated molecular pathways are involved in the development of DR. Microvesicles (MVs) are cell membrane vesicles, which carry many biologic molecules, such as mRNAs, microRNA...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2017.77
更新日期：2018-01-01 00:00:00
abstract：AIM:In order to elucidate the molecular mechanism underlying the cardioprotection afforded by schisandrin B (Sch B), the effect of Sch B treatment on the sensitivity of mitochondria to Ca2+-stimulated permeability transition (PT) was investigated in rat hearts under normal and ischemia-reperfusion (I-R) conditions. RE...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00614.x
更新日期：2007-10-01 00:00:00
abstract：:Innovative teaching methodologies in different parts of the world are being practiced since last 3 decades. The aim of this review is to report the transition from traditional to innovative self learning process in Ziauddin Medical University, a new medical institute of Pakistan. Various problems encountered have been...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-09-01 00:00:00
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：:Neuritin is a member of the neurotrophic factor family, which is activated by neural activity and neurotrophins, and promotes neurite growth and branching. It has shown to play an important role in neuronal plasticity and regeneration. It is also involved in other biological processes such as angiogenesis, tumorigenes...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2017.197
更新日期：2018-09-01 00:00:00
abstract：AIM:To investigate the effects of small interfering RNA of cyclooxygenase-2 (COX-2) on the proliferation and apoptosis of human multiple myeloma RPMI8226 cells and its relation with the Bcl-2 family in vitro. METHODS:Transcription and expression of COX-2 in human myeloma RPMI8226 cells were checked by RT-PCR and Weste...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00550.x
更新日期：2007-07-01 00:00:00
abstract：AIM:To isolate the G4 and G1 molecular forms of acetylcholinesterase in rat cortex for interpreting the therapeutical effect of the AChE inhibitor drugs. METHODS:Size exclusion chromatography and ultracentrifugation were used to isolate and ascertain the G4 and G1 molecular forms of AChE. RESULTS:After size exclusion...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2002-02-01 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 construct an HEK293 cell line stably expressing human dopamine D1 receptor (D1R). METHODS:cDNA was amplified by RT-PCR using total RNA from human embryo brain tissue as the template. The PCR products were subcloned into the plasmid pcDNA3 and cloned into the plasmid pcDNA3.1. The cloned D1R cDNA was sequenced a...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00017.x
更新日期：2005-01-01 00:00:00
abstract：:Liver fibrosis is excessive accumulation of extracellular matrix proteins that results from various chronic liver diseases. Hepatic stellate cells (HSCs) play an essential role in the pathogenesis of liver fibrosis. Danggui Buxue Tang (DBT) is a classic formula of Chinese traditional medicine. We previously showed tha...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2017.175
更新日期：2018-09-01 00:00:00
abstract：AIM:To investigate the effects of co-delivering IL-6 expressing plasmid pCI-IL-6 on the immunogenicity of the anti-caries DNA vaccine pCIA-P, which encodes the surface protein antigen PAc of Streptococcus mutans. METHODS:Plasmid pCI-IL-6 was constructed by inserting the murine IL-6 gene into the pCI vector. Expression...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2013.184
更新日期：2014-05-01 00:00:00
abstract：AIM:Endothelium-dependent relaxations to certain neurohumoral substances are mediated by pertussis toxin-sensitive Gi/o protein. Our experiments were designed to determine the role, if any, of pertussis toxin-sensitive G-proteins in relaxations attributed to endothelium-derived hyperpolarizing factor (EDHF). METHODS:P...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00905.x
更新日期：2008-12-01 00:00:00
abstract：AIM:To investigate the effects of salvianolate, a water-soluble active compound from Salvia miltiorrhiza Bunge, on reactive oxygen species (ROS) production in mouse cardiomyocytes in vitro. METHODS:Primary ventricular cardiomyocytes were prepared from neonatal mouse. The cell viability was determined using MTT assay. ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2012.209
更新日期：2013-04-01 00:00:00
abstract：AIM:To compare high K(+ )-induced contraction and optimal resting tension measured by two commonly used techniques of hypertonic and isotonic K(+ ) in aortas with and without adventitial fat from various age rats. METHODS:Three age groups of rats (15, 25, and 62 weeks) were used to prepare thoracic aortic rings in whi...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00548.x
更新日期：2007-05-01 00:00:00
abstract：:As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capaci...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/s41401-020-0415-5
更新日期：2020-07-01 00:00:00
abstract：AIM:To study whether etodolac enantiomers have pharmacokinetic difference after oral administration. METHODS:Fourteen rats, divided into two groups randomly, were orally given S-(+)- or R-(-)-etodolac at a single dose of 20 mg/kg, respectively. Blood samples were collected before and at 5, 10, 20, 30 min and 1, 3, 6, ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：
更新日期：2004-08-01 00:00:00
abstract：AIM:To examine the protective effect of propofol in renal ischemia/reperfusion (I/R) injury and the role of heme oxygenase-1 (HO-1) in this process. METHODS:Sprague-Dawley rats were randomly divided into 3 groups: (i) sham-operated group; (ii) I/R group; and (iii) propofol group. Bilateral renal warm ischemia for 45 m...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2007.00566.x
更新日期：2007-08-01 00:00:00
abstract：AIM:To study effects of arachidonic acid (AA) and its metabolites on the hyposmotic membrane stretch-induced increase in calcium-activated potassium currents (I(KCa)) in gastric myocytes. METHODS:Membrane currents were recorded by using a conventional whole cell patch-clamp technique in gastric myocytes isolated with ...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2005.00201.x
更新日期：2005-10-01 00:00:00
abstract：AIM:To investigate the anticancer effect of crocetin, a major ingredient in saffron, and its underlying mechanisms. METHODS:Cervical cancer cell line HeLa, non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine. Cell proliferatio...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/aps.2011.109
更新日期：2011-12-01 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,...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1038/s41401-018-0066-y
更新日期：2019-01-01 00:00:00
abstract：:Specific chromosome aberrations are frequently detected during the development of hepatocellular carcinoma. Molecular cytogenetic approaches such as comparative genomic hybridization and loss of heterozygosity analyses have provided fruitful information on changes in HCC cases at the genomic level. Mapping of chromoso...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1111/j.1745-7254.2005.00126.x
更新日期：2005-06-01 00:00:00
abstract：AIM:To investigate whether IL-12p40 plays a crucial role in regulating islet allograft rejection in a streptozotocin (STZ)-induced diabetes mouse model. METHODS:C57BL/6 and IL-12p40 gene knockout mice were selected as recipient mice, to which the diabetes was induced with a treatment of STZ (150-200 mg/kg) by a single...
journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章
doi：10.1111/j.1745-7254.2006.00341.x
更新日期：2006-08-01 00:00:00
