FITOTERAPIA
·
2025
·
IF 2.6
Li Zhang,Hui Wu,Xiaoyuan Li,Xiu Zhang,Hua Li,Huaqiao Tang,Daxuan Tang,Shijing Du,Ya’’ou Liu,Yangfan Tang,Xiaoming Bao,Guoqiang Cheng
Qianghuo (the rhizomes and radixes of Notopterygium incisum Ting ex H.T. chang) is a traditional Chinese medicine, and widely used as an anti-inflammatory, anodyne, antifebrile agent. Qianghuo volatile oil also exhibits the same properties, and the effects are probably related to the inhibition of cyclooxygenase (COX), but its bioactive components are not clear yet. To figure out the bioactive components of Qianghuo volatile oil target to cyclooxygenase-2 (COX-2), a ligand fishing method using immobilized COX-2 magnetic beads (COX-2-MB S ) and gas chromatography–mass spectrometry (GC–MS) were developed to identify the compounds that act on COX-2. Nine ligands, including 3-carene, β-caryophyllene, eucalyptol, α-terpinene, Limonene, δ-terpinene, α-pinene, β-pinene and γ-terpinene, were specifically captured by COX-2-MB S . Among them, 3-carene, β-caryophyllene, and eucalyptol in Qianghuo volatile oil were isolated and confirmed by in vitro inhibition and in vivo anti-inflammatory activity assays as selective inhibitor against COX-2. The IC 50 values were 13.5, 10.1, and 7.6 μM, respectively. Compared with the model, 3-carene, β-caryophyllene, and eucalyptol considerably reduced ear swelling and paw edema. Moreover, 3-carene and eucalyptol significantly decreased the changes of COX-2 expression in RAW264.7 cells activated by LPS. Our study validated that the developed ligand-fishing method using COX-2-MBs coupled with GC–MS can be applied to recognize COX-2 inhibitors in Qianghuo volatile oil. In vitro/vivo assay showed 3-carene and eucalyptol in Qianghuo volatile oil had strong inhibition against COX-2. This study may provide novel methods for discovering active components for volatile oil–based drug development or aromatherapy.
研究领域:
中药学
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生物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
ChemMedChem
·
2025
·
IF 3.4
Xinlin Zhu,Qin Li,Junhui Wu,Zhiran Ju
Graphical In recent years, the development of COX-2 inhibitors has shifted from a focus on highly selective inhibition to emphasizes more moderate selectivity. This study presents a potent balanced COX-2 inhibitor, compound 21d, which effectively alleviates histological damage and provides protection against DSS-induced colitis. The severe adverse effects associated with imbalanced cyclooxygenase-2 (COX-2) inhibition continue to pose significant challenges in the development of contemporary anti-inflammatory drugs. In recent years, the approach to COX-2 inhibitor drug development has shifted from a focus on highly selective inhibition of COX-2 to a strategy that emphasizes more moderate selectivity. The amino acid sequence and structural similarities between inducible COX-2 and constitutive cyclooxygenase-1 (COX-1) isoforms present both substantial opportunities and challenges for the design of next generation of balanced COX-2 inhibitors. As part of our ongoing research into the discovering novel and safer COX-2 inhibitors, we reported herein a highly potent and balanced COX-2 inhibitor 21 d (IC 50 value=1.35 μM, selectivity profile (IC 50 (COX-1)/IC 50 (COX-2)=22.34)). In vivo assays demonstrated that 21 d significantly alleviated histological damage and provided robust protection against dextran sulfate sodium (DSS)-induced acute colitis.
研究领域:
药理学
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分子生物学
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药物开发
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Fei Tong,Bo Dong,Rongkui Chai,Ke Tong,Yini Wang,Shipiao Chen,Xinmei Zhou,Daojun Liu
The purpose of the research was to explore the therapeutic action of simvastatin-loaded poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) (PEG-b-PBLG50) on intestinal ischemia/reperfusion injury (II/RI) through downregulating bone morphogenetic protein 4 (BMP4)/cyclooxygenase-2 (COX-2) pathway as compared to free simvastatin (Sim). Sprague Dawley rats were preconditioned with 20 mg/kg Sim or simvastatin/PEG-b-PBLG50 (Sim/P) compounds, and then subjected to 45 min of ischemia and 1 h of reperfusion. The blood and small intestines were collected, serum levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α, and nitric oxide (NO) were checked, and the dry/wet intestine ratios, superoxide dismutase activity, myeloperoxidase content, reactive oxygen species, endothelial nitric oxide synthase, protein 47 kDa phagocyte oxidase (p47phox), BMP4, COX-2, and p38 mitogen-activated protein kinase (p38MAPK) expressions were measured in intestinal tissues. Both Sim and Sim/P pretreatment reduced intestinal oxidative damnification, restricted inflammatory harm, and downregulated the BMP4 and COX-2 expressions as compared to II/RI groups, while Sim/P remarkably improved this effect.
研究领域:
药理学
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病理学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Rui Hu,Xin Jiang,Lijie Zhu,Rui Meng,Rongbo Yang,Wenjie Sun,Zhenzhou Zhao,Yuehua Lyu,Ruoyuan Huang,Fei Xue,Mengke Shi,Zaigang Zhou,Jianliang Shen,Congying Xie
Currently, certain lung cancer patients exhibit resistance to radiotherapy due to reduced DNA damage under hypoxic conditions and the cytoprotective and immune-resistance effect caused by increased programmed death ligand-1 (PD-L1) and Cyclooxygenase 2 (COX-2) expression after radiotherapy. At present, existing nanoparticles or drugs could hardly effectively, and easily address these obstacles faced by highly effective radiotherapy simultaneously, especially the simultaneous depression of PD-L1 and COX-2. In this study, it is newly proved that some typical nitric oxide (NO) gas donors could co-inhibit PD-L1 and COX-2 expression, revealing the possible not fully proven role of NO in reversing tumor immunotherapy resistance. Then, to realize selective NO generation in tumors, a simple tumor glutathione (GSH) responsive NO gas nanogenerator named SAB-NO nanoparticles was designed and prepared, which was composed of the NO donor Isoamyl Nitrite conjugated with serum albumin (SAB). By doing this, SAB-NO nanoparticles more effectively sensitized radiotherapy through breaking the cytoprotective effects faced by radiotherapy in vitro by generating more DNA damage through reversing tumor hypoxia and impairing the DNA damage repair process through decreasing PD-L1 expression. Then, the combination therapy of SAB-NO nanoparticles and radiotherapy effectively transformed cold tumors into hot ones through avoiding some potential immune-resistance effects induced by radiotherapy treatment alone through PD-L1 and COX-2 co-inhibition. In conclusion, the combined treatment of radiotherapy and SAB-NO nanoparticles finally almost completely suppressed the growth of lung tumors, revealing the novel role of NO donors in sensitizing tumor immunotherapy by avoiding the potential cytoprotective and immune-resistance effects.
研究领域:
肿瘤学
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免疫学
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药剂学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6
Zhiran Ju,Junde Xu,Keshuang Tang,Fener Chen
COX-2/NLPR3-targeted therapy might be beneficial for the inflammation diseases. To discover novel anti-inflammatory compounds with favorable safety profiles, three new series of non-carboxylic diclofenac analogues bearing various ring systems, such as oxadiazoles 4a - 4w , triazoles 6a - 6m , and cyclic imides 7a and 7b , were synthesized. The synthesized analogues were evaluated for their inhibitory activity against COX-2 enzyme. Among them, compound 6k exhibited potent selective COX-2 inhibition (IC 50 = 1.53 μM; selectivity ((IC 50 (COX-1)/IC 50 (COX-2) = 17.19). Treatment with compound 6k effectively suppressed the NF-κB/NLRP3 signaling pathway, resulting in reduced expression of pro-inflammatory factors. The in vivo ulcerative colitis assay demonstrated that compound 6k significantly ameliorated histological damages and showed strong protection against DSS-induced acute colitis. The collected results indicated that compound 6k displays anti-inflammatory activity through COX-2/NLRP3 inhibition. Therefore, compound 6k represents a promising candidate for further development as a new lead compound with reduced colitis side effects.
研究领域:
药理学
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药物化学
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炎症研究
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Yongyan Zhu,Ao Duan,Qianqian Yu,Shuo Tian,Zishan Zhou,Ping Li,Dongmei Pan,Huaming Tao,Quanhong Zhu
Ethnopharmacological relevance Fangji Huangqi Decoction (FHD) is a classical Chinese compound formula for treating rheumatoid arthritis (RA) with satisfactory effects. FHD is reputed for its ability to tonify qi with strengthening exterior, and dispel wind while removing dampness, but its mechanisms and bioactive compounds for treating RA remain unclear. Aim of the study The aim of this study was to explore the key target and bioactive compounds that were responsible for FHD-mediated improvements in RA. Materials and methods Using network pharmacology, we discovered that cyclooxygenase-2 (COX-2) was the key target of FHD against RA. We utilized a ligand fishing technique with COX-2 immobilized magnetic beads to recognize the bioactive components that act on COX-2. Then we carried out an in vitro assay of COX-2 enzyme inhibition and in vivo assay of carrageenan-induced inflammation and collagen-induced arthritis (CIA) to validate the bioactive effects of these captured ingredients. In the CIA assay, micro-CT, hematoxylin‒eosin staining and safranin-O/fast green staining were employed to assess the influence of the captured ligand on bone damage, pathological injury and cartilage destruction, respectively. Immunohistochemistry (IHC) and enzyme-linked immunosorbent assays (ELISAs) were used to detect the expression of COX-2 target in the ankle joint. interleukin-6 (IL-6) levels in the serum were also detected by ELISA. Molecular docking was used to reveal the binding mechanism of the COX-2 protein and the captured ligand. Results Eleven ligands, including tetrandrine, fangchinoline, cyclanoline, licochalcone B, ononin, calycosin and liquiritin, were specifically bound to the COX-2 protein, as determined by ultrahigh-performance liquid chromatography–mass spectrometry (UPLC–MS), seven of which were present at high levels. One ligand, tetrandrine, not only had a great inhibitory effect on COX-2 enzyme activity but also significantly reduced carrageenan-induced inflammation. In the CIA assay, middle- and high-dose tetrandrine (25 and 50 mg/kg) had effects comparable to those of FHD and celecoxib on ameliorating RA symptoms in CIA mice via the COX-2 target. Furthermore, compared with the low-dose tetrandrine group (12.5 mg/kg), the FHD group exhibited significantly lower arthritis index scores and serum IL-6 expression, although the content of tetrandrine in FHD extract solution was approximately 0.1% of that in the low-dose tetrandrine group. Conclusions Hence, we inferred that tetrandrine was the main bioactive component responsible for the effects of FHD against RA by suppressing the expression of the COX-2 protein and inhibiting the enzyme catalytic activity of COX-2. The reason for these effects may be that tetrandrine can interact with the residue Tyr385 of COX-2, the enzymatic catalytic site of COX-2 to transform arachidonic acid (AA) to prostaglandin E2 (PGE2), and thereby reduce the production of prostaglandins and inflammatory metabolites. Moreover, in addition to tetrandrine, FHD contains other compounds that could supplement the activity of tetrandrine when FHD was used to treat RA, which is manifested the “multi-component” characteristic of how Traditional Chinese Medicine formulas treat diseases.
研究领域:
民族药理学
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药物化学
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炎症研究
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DOI
PubMed
高影响因子
FEBS Journal
·
2019
·Vol. 287
·期 8
·1666-1680
·
IF 4.739
Chen-Yu Zhang,Jia-Xi Duan,Hui-Hui Yang,Chen-Chen Sun,Wen-Jing Zhong,Jia-Hao Tao,Xin-Xin Guan,Hui-Ling Jiang,Bruce D. Hammock,Sung Hee Hwang,Yong Zhou,Cha-Xiang Guan
Pulmonary fibrosis (PF) is a senescence-associated disease with poor prognosis. Currently, there is no effective therapeutic strategy for preventing and treating the disease process. Mounting evidence suggests that arachidonic acid (ARA) metabolites are involved in the pathogenesis of various fibrosis. However, the relationship between the metabolism of ARA and PF is still elusive. In this study, we observed a disorder in the cyclooxygenase-2/cytochrome P450 (COX-2/CYP) metabolism of ARA in the lungs of PF mice induced by bleomycin (BLM). Therefore, we aimed to explore the role of COX-2/CYP-derived ARA metabolic disorders in PF. PTUPB, a dual COX-2 and soluble epoxide hydrolase (sEH) inhibitor, was used to restore the balance of COX-2/CYP metabolism. sEH is an enzyme hydrolyzing epoxyeicosatrienoic acids derived from ARA by CYP. We found that PTUPB alleviated the pathological changes in lung tissue and collagen deposition, as well as reduced senescence marker molecules (p16 Ink4a and p53-p21 Waf1/Cip1 ) in the lungs of mice treated by BLM. In vitro , we found that PTUPB pretreatment remarkably reduced the expression of senescence-related molecules in the alveolar epithelial cells (AECs) induced by BLM. In conclusion, our study supports the notion that the COX-2/CYP-derived ARA metabolic disorders may be a potential therapeutic target for PF via inhibiting the cellular senescence in AECs.
研究领域:
药理学
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肺病学
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分子生物学
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治疗学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Xingfang Zhang,Liang Gao,Jianv Wang,Wei Zhang,Dong Xu,Yanhua Wang,Tianlong Liu,Kai Gao,Zhen Ren,Yi Ding
β-Bisabolene, a bioactive sesquiterpene extracted from myrrh—a substance utilized for ischemic stroke treatment—has known therapeutic potential. Nevertheless, the exact mechanisms underlying its beneficial effects on ischemic stroke, along with its potential targets, remain to be fully elucidated. This study aimed to investigate the therapeutic potential of β-Bisabolene in ameliorating ischemic stroke, identify its potential targets and interactions, and explore the underlying pathways involved. Bioinformatics analyses, including network pharmacology and analysis of GEO transcriptomic datasets, were performed to predict the potential targets and mechanisms of β-Bisabolene in ischemic stroke treatment. Preliminary computational validation was achieved through molecular similarity comparisons, molecular docking studies, and molecular dynamics simulations. In vitro experiments were then conducted to confirm the protective effects of β-Bisabolene on microglia injured by oxygen‒glucose deprivation and to validate the findings from the bioinformatics analyses. The results revealed that β-Bisabolene reduces the levels of the proinflammatory cytokines TNF-α, IL-1β and NO; decreases reactive oxygen species levels; and decreases the expression of COX-2, P38, ERK and Keap1. Moreover, it increases the expression of Arg-1, Nrf2, NQO1 and HO-1. These effects are associated with improved survival rates of oxygen–glucose deprivation–damaged microglia. In conclusion, β-Bisabolene may exert anti-inflammatory and antioxidant effects to ameliorate microglial injury induced by ischemic stroke by antagonizing COX-2 and mediating the MAPK signaling pathway and Keap1/Nrf2 pathway. This study provides valuable insights into the therapeutic potential of β-Bisabolene for the treatment of ischemic stroke.
研究领域:
药理学
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神经科学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 15
·e70778
·
IF 4.2
Hong Tang,Qi Dai,Ziyan Zhao,Weiye Ge,Danlei Li,Zelin Chang,Penglai Pi,Jia Li,Zheng Sun
Glioblastoma (GBM) is an aggressive and highly malignant primary brain tumour, accounting for a significant proportion of adult brain tumours. It is associated with a poor prognosis and high recurrence rates. Although temozolomide (TMZ) remains the standard first-line chemotherapy for GBM, its clinical efficacy is often limited by the development of drug resistance and toxic effects on normal tissues. Melatonin (Mel), a natural indoleamine synthesised by the pineal gland, has demonstrated synergistic anti-tumour effects when combined with various chemotherapy agents in multiple studies. This study investigates the synergistic potential of Mel to enhance TMZ's therapeutic efficacy against GBM. The results demonstrate that the combination of Mel and TMZ significantly inhibits glioblastoma cell proliferation, migration, and invasion. Mechanistically, this synergistic effect is mediated through the NF-κB/COX-2 signalling pathway. Mel enhances TMZ's anti-tumour activity by inhibiting IκBα phosphorylation, suppressing NF-κB activation, and downregulating COX-2 expression. Additionally, the combination treatment induced apoptosis via activation of the Caspase-3 pathway. These results suggest that Mel can potentiate the therapeutic efficacy of TMZ in glioblastoma treatment, offering a promising strategy to overcome TMZ resistance while reducing its associated toxicity.
研究领域:
肿瘤学
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药理学
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神经病学
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分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2018
·
IF 3.974
Peng Chen,Na Geng,Dong Zhou,Yiran Zhu,Yuliang Xu,Kangping Liu,Yongxia Liu,Jianzhu Liu
Hexavalent chromium (Cr(VI)) is a common environmental pollutant. Exposure of Cr(VI) can lead to cell autophagy, but the preventive measures for diminishing Cr(VI)-induced autophagy need further study. COX-2 can be induced by several heavy metals and can lead to endoplasmic reticulum (ER) stress and autophagy; thus, COX-2, ER stress, and autophagy may be related. This study mainly investigated the role of COX-2 in the eIF2α-ATF4 pathway, which is a major pathway in cell autophagy. In this study, Cr(VI) was used as a xenobiotic to determine changes in the parameters of ER stress, autophagy, and COX-2 levels. At the same time, a clear contrast was obtained by assigning positive and negative controls of ER stress and autophagy. The results showed that during Cr(VI) invasion, the parameters of ER stress and autophagy (such as BiP, PERK, p62, LC3-II, and mTOR) were enhanced, similarly to the positive control of ER stress and/or the autophagy controls. Such enhancement is a protective mechanism for cell survival. Additionally, the COX-2 levels increased. Moreover, when COX-2 was inhibited, the PERK level remained high, whereas the LC3-II level decreased. This finding suggests that COX-2 specifically affects the interaction between ER stress and autophagy. Notably, this study reveals that Cr(VI) can induce ER stress and autophagy in DF-1 cells and that COX-2 plays an essential role in the interaction between ER stress and autophagy.
研究领域:
毒理学
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细胞生物学
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环境科学
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2020
·
IF 4.831
Bo Zhang,Xiu-Ting Hu,Kang-Min Zhou,Yu-Shun Yang,Hai-Liang Zhu
Cyclooxygenase is critical for maintaining physiological functions, whereas overexpression of COX-2 was closely implicated in various cancers. In this study, a series of novel aminophosphonate derivatives containing pyrazole moiety were synthesized with their anti-cancer activity evaluated. In vitro assays of the target compounds showed that Z21 displayed excellent COX-2 inhibitory activity against COX-2 (IC 50 = 0.22 ± 0.04 µM) and anti-proliferative activity against MCF-7 cell (IC 50 = 4.37 ± 0.49 µM). The apoptosis induction of compound Z21 was confirmed by flow cytometry and polymerase chain reaction. Further investigation demonstrated that compound Z21 induced apoptosis of MCF-7 cells through a mitochondrion-dependent pathway and involved cell-cycle arrest in G2 phase. Overall, these results provided some new insights into the design of therapeutic drugs for COX-2 inhibitors and indicated the connection between selective COX-2 inhibition and the anti-tumor activity.
研究领域:
药理学
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肿瘤学
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药物化学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR DIVERSITY
·
2025
·
IF 3.8
Miao Wenjun,Yang Meixian,Peng Zhiping,Xia Zhu,Zhang Xiaoyang,Chen Yi,Jia Jianhua
Cyclooxygenase-2 (COX-2) plays vital roles in promoting angiogenesis, tissue invasion, and resistance to apoptosis, so it has become an attractive biomarker for imaging and therapy of cancer. Numerous radio-tracers for detection of COX-2 in vivo have been reported, but no one has been successfully applied in clinic. In this study, the radiosynthesis and evaluation of [ 18 F] 6 , containing a 1,5-diarylpyrrole structure, as a radiotracer for imaging of COX-2 is described. [ 18 F] 6 was prepared within 90 min synthesis time with radiochemical yields (RCYs) of 2–6% (n = 7, decay corrected) from [ 18 F]fluoride by a one-step 18 F-trifluoromethylation reaction. After purification by high performance liquid chromatography (HPLC), its radiochemical purity (RCP) was higher than 98%, and the molar activity was 156–210 MBq/mmol. The stability of [ 18 F] 6 was determined by incubation in saline and fetal bovine serum (FBS) in vitro, showing excellent stability in 4 h. The specific binding of [ 18 F] 6 was evaluated using MCF-7 cells (COX-2 positive cells) in vitro, where the radiotracer uptake was blocked in the presence of Celecoxib (a commonly used COX-2 inhibitor). However, no tumor accumulation of [ 18 F] 6 could be observed by micro-PET/CT studies on MCF-7 tumor-bearing mice in vivo. This may be due to the insufficient molar activity of [ 18 F] 6, or inadequate expression of COX-2 in MCF-7. In conclusion, optimizations of radiosynthesis and evaluations of specific binding in suitable model are further still needed to verify the potential of [ 18 F] 6 as a COX-2 imaging agent.
研究领域:
分子影像学
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核医学
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药物化学
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肿瘤学
·
放射化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）