Abstract:
AIM:To characterize the in vitro bioactivities of rhodanine derivatives as novel peroxisome proliferator-activated receptor (PPAR) gamma modulators, based on a hit (SH00012671) identified during high-throughput screening (HTS) of a diverse synthetic compound library, and to preliminarily elucidate the structure-activity relationship of this class of PPARgamma agonists. METHODS:Full-length PPARgamma and retinoid X receptor alpha (RXRalpha), biotinylated PPAR response element (PPRE), [3H]BRL49653 (rosiglitazone), and streptavidin-coated FlashPlate or microbeads were used to measure the receptor-binding properties of various compounds based on the scintillation proximity assay (SPA) technology. A recombinant PPRE vector was transiently cotransfected with PPARgamma and RXRalpha plasmids into the African green monkey kidney (CV-1) cells, and the effects of BRL49653 and test compounds on transcription mediated by PPARgamma were determined by examining luciferase (reporter) responses. 3T3-L1 cells were employed to determine whether the compounds facilitated adipogenesis upon PPARgamma activation. RESULTS:Of the 16,000 samples screened with the SPA method, only 1 compound (SH00012671) displayed a similar binding affinity (Ki=186.7 nmol/L) to PPARgamma as BRL49653, but it was inactive in the cell-based assays. A series of rhodanine derivatives were synthesized based on the core structure of SH00012671 and 8 of them showed agonist activities in both cotransfection and pre-adipocyte differentiation assays. To reduce intrinsic cytotoxicities, the sulphur on the rhodanine was changed to oxygen. This alteration led to a decrease in receptor-binding affinities while modified analogues generally maintained agonist efficacies in the cell-based assays. Of the analogues studied, compound 31 exhibited about 70% the efficacy exerted by BRL49653 in both cotransfection and pre-adipocyte differentiation assays. CONCLUSION:Through minor chemical modifications on the core structure of the initial HTS hit, SH00012671 was transformed to possess both molecular (PPARgamma binding) and cellular (adipogenesis) activities. The rhodanine derivatives reported here may represent a new scaffold in further understanding the molecular mechanism of agonism at PPARgamma.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Liu Q,Zhang YY,Lu HL,Li QY,Zhou CH,Wang MWsubject
Has Abstractpub_date
2007-12-01 00:00:00pages
2033-9issue
12eissn
1671-4083issn
1745-7254journal_volume
28pub_type
杂志文章abstract:AIM:To investigate whether low dose theophylline has an anti-inflammatory effect in asthma. METHODS:Nineteen asthmatic subjects were given 200 mg sustained-release theophylline preparation twice daily for 4 weeks. The mean serum concentration of theophylline was 7.9 mg/L. The percentage of eosinophils, EG2+ eosinophil...
journal_title:Acta pharmacologica Sinica
pub_type: 临床试验,杂志文章
doi:
更新日期:2001-05-01 00:00:00
abstract:AIM:(-)Stepholidine (SPD) is an active ingredient of the Chinese herb Stephania intermedia, which binds to the dopamine D(1) and D(2) like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D(1) and a D(2) antagonist, which could make SPD a unique a...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00365.x
更新日期:2006-09-01 00:00:00
abstract:AIM:To investigate the effects of trans-cinnamaldehyde (TCA) on the human leukemia K562 cell line and the cytotoxicity of cytokine-induced killer (CIK) cells against K562 cells. METHODS:Apoptosis, Fas expression, and mitochondrial transmembrane potential in K652 cells were analyzed using flow cytometry. K562 cells wer...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.76
更新日期:2010-07-01 00:00:00
abstract:AIM:To investigate the expression of advanced glycation end products (AGEs) and their receptor RAGE in the livers and blood vessels of rats with non-alcoholic steatohepatitis (NASH) and the effect of pentoxifylline (PTX) on liver and artery function in rats with NASH. METHODS:Sprague-Dawley rats were fed a high-fat di...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.110
更新日期:2010-10-01 00:00:00
abstract:AIM:To study the protein and mRNA expressions of pro-inflammatory and anti-inflammatory cytokines in the brain of rats with atherosclerosis (AS) and the effects of Ginkgo biloba extract (GbE) on expressions of cytokines. METHODS:The experimental model of AS in rats were established by intraperitioneal injection of vit...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00106.x
更新日期:2005-07-01 00:00:00
abstract:AIM:To investigate the role of CYP2E1 in isoniazid (INH)-induced hepatotoxicity and the influence of rifampicin (RFP) on INH-induced liver injury. METHODS:Rats were treated with INH alone (100 mg/kg, ip) or co-administered with RFP (100 mg/kg, ig) for 10 d and 21 d. Hepatotoxicity was assayed by plasma enzymes (sALT, ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-05-01 00:00:00
abstract:AIM:To study the regulation of monoamine oxidase-B (MAO-B) activity and imidazoline receptors (I-R) during long term treatment of morphine. METHODS:MAO-B activity was detected by high performance liquid chromatography; I-R was detected by [3H]idazoxan binding test. RESULTS:Idazoxan and morphine inhibited whole brain ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract::Pre-B-cell leukemia transcription factor 3 (PBX3) is a member of the PBX family and contains a highly conserved homologous domain. PBX3 is involved in the progression of gastric cancer, colorectal cancer, and prostate cancer; however, the detailed mechanism by which it promotes tumor growth remains to be elucidated. H...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-00599-9
更新日期:2021-02-01 00:00:00
abstract:AIM:To examine the effects of β3-adrenoceptor (β3-AR) activation on atherosclerotic plaque development in ApoE(-/-) mice. METHODS:Thirty six week-old male ApoE(-/-) mice on a high-fat diet were treated with atorvastatin (10 mg·kg(-1)·d(-1), po), BRL37344 (β3-AR agonist, 1.65 or 3.30 μg/kg, ip, twice a week) or SR52390...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2013.70
更新日期:2013-09-01 00:00:00
abstract:AIM:To study the effect of adenovirus5-mediated human hepatocyte growth factor (Ad(5)-HGF) transfer on post-infarct heart failure in a swine model. METHODS:Twelve young Suzhong swine were randomly divided into 2 groups: the Ad(5)-HGF group (n=6) and the null-Ad(5) group (n=6). Four weeks after left anterior descending...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00306.x
更新日期:2006-05-01 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 investigate the effects of different muscarinic receptor (M) subtypes in the spinal cord on the scores of naloxone-precipitated morphine-withdrawal symptoms and the changes of nNOS expression in locus coeruleus (LC). METHODS:nNOS immunohistochemistry, intrathecal injection (it), and antisense oligonucleotides (...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract::The mechanism underlying the resistance of cancer cells to chemotherapeutic drug varies with different cancer cells. Recent evidence shows that lysosomal function is associated with drug resistance of cancer cells. Artesunate, a derivative of artemisinin, displays broad antitumor activity and direct cytotoxicity on va...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-020-0445-z
更新日期:2020-07-23 00:00:00
abstract:AIM:To develop a simple method for monitoring protein localization of epidermal growth factor (EGF) in living cells. METHODS:Enhanced green fluorescent protein (EGFP) was used as an autofluorescent tag to label EGF ligands. SDS-PAGE and Western blot analysis were used to detect the expression of the EGFP-tagged EGF (E...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00481.x
更新日期:2007-01-01 00:00:00
abstract:AIM:To investigate the anti-neuroinflammatory activity of a novel synthetic compound, 7-methylchroman-2-carboxylic acid N-(2-trifluoromethyl) phenylamide (MCAP) against LPS-induced microglial activation in vitro. METHODS:Primary mouse microglia and BV2 microglia cells were exposed to LPS (50 or 100 ng/mL). The express...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.138
更新日期:2016-03-01 00:00:00
abstract:AIM:To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats. METHODS:Chronic transauricular kindling was induced by repeated application of initially subcon...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00220.x
更新日期:2005-11-01 00:00:00
abstract::Over half of patients with BRCA1-deficient cancers do not respond to treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. In this study, we report that a combination of 53BP1 and BRCA1 may serve as a biomarker of PARP inhibitor sensitivity. Based on the mRNA levels of four homologous recombination repair (HR)...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2017.8
更新日期:2017-07-01 00:00:00
abstract:AIM:To investigate the effect of melittin (Mel) on papillary muscles of guinea pigs. METHODS:Contraction of papillary muscles were examined by conventional method and action potentials (AP) were recorded by standard glass microelectrode technique. RESULTS:Mel (0.5, 3 micromol/L) significantly increased the contractil...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-08-01 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 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: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
abstract:AIM:To study the effect of nomegestrol acetate, a new synthetic progesterone on granulosa cells' viability and steroidogenesis function. METHODS:Granulosa cells were cultured in McCoy's 5A medium. Trypan blue stain was used to measure viable cells. FSH and testosterone were added to stimulate the steroid secretion. Sp...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservati...
journal_title:Acta pharmacologica Sinica
pub_type: 历史文章,杂志文章,评审
doi:10.1038/aps.2017.182
更新日期:2018-05-01 00:00:00
abstract:AIM:To study the effects of nimodipine on delayed cerebral injury in mice from subacute carbon monoxide (CO) exposure. METHODS:Mice were exposed to CO (100 mL/kg, ip) once a day, continuously for 7 d. After 7-d CO-exposure, mortality in mice, changes in learning ability and memory using passive avoidance test, the pat...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-05-01 00:00:00
abstract::Cysteine-rich peptides from the venom of cone snails (Conus) target a wide variety of different ion channels. One family of conopeptides, the alpha-conotoxins, specifically target different isoforms of nicotinic acetylcholine receptors (nAChRs) found both in the neuromuscular junction and central nervous system. This ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2009.47
更新日期:2009-06-01 00:00:00
abstract::Monoclonal antibodies are believed to be magic bullets and hold great potential for lots of biological process. About 100 μg of mAb109 was expressed in 5 × 106 cells after 10 days' immunization. 64Cu-NOTA-mAb109 was synthesized with the specific activity of 0.74 MBq/μg and high in vitro stability. The binding affinity...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0294-9
更新日期:2020-01-01 00:00:00
abstract:AIM:To investigate the effects of resveratrol on interleukin-1beta (IL-1beta) induced catabolism in bone marrow mesenchymal stem cell (MSC) derived chondrocytes cultured on chitosan-gelatin scaffolds (CGS). METHODS:The chondrogenesis of alginate-encapsulated MSCs was evaluated by toluidine blue staining, RT-PCR, and i...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00880.x
更新日期:2008-11-01 00:00:00
abstract:AIM:The mechanism of tramadol-induced vasodilation was investigated using isolated rabbit thoracic aortic rings. METHODS:Aortic rings from 8 rabbits were placed in organ bath and precontracted with phenylephrine (10(-5) mol/L) before addition of tramadol. Relaxation responses by tramadol were evaluated in the presence...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-05-01 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 evaluate retrospectively the association of cytochrome P450 3A (CYP3A) and ATP-binding cassette sub-family B member 1 (ABCB1) gene polymorphisms with the pharmacokinetics of cyclosporine A (CsA) in Chinese renal transplant patients. METHODS:One hundred and twenty-six renal transplant patients were recruited. Bl...
journal_title:Acta pharmacologica Sinica
pub_type: 临床试验,杂志文章
doi:10.1038/aps.2012.136
更新日期:2012-12-01 00:00:00