1.Vulnerable plaque and internal atherosclerosis plaque angiogenesis.
Chinese Journal of Integrated Traditional and Western Medicine 2007;27(12):1140-1143
The instability of atherosclerotic plaque would lead to the rupture of plaque, even acute coronary syndrome (ACS). To prevent the internal atherosclerosis plaque angiogenesis may play a very important role in stabilizing the vulnerable plaque. Traditional Chinese drugs show potential advantages in stabilizing AS plaque by its characteristics of multi-way, multi-link and multi-target all-sided treatment.
Animals
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Arteriosclerosis
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classification
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pathology
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Coronary Artery Disease
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pathology
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prevention & control
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Drugs, Chinese Herbal
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therapeutic use
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Humans
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Medicine, Chinese Traditional
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methods
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Neovascularization, Pathologic
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prevention & control
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Phytotherapy
2.Current situation, problem analyses and its countermeasure of formulae of traditional Chinese medicine (FTCM) preventing and curing tumor angiogenesis.
Shengyan XI ; Yanhui WANG ; Yufang ZHAO ; Dawei LU ; Pengcheng LI ; Qian ZHANG
China Journal of Chinese Materia Medica 2010;35(10):1352-1356
Malignant tumor is the common disease that threaten severely to people's health. Formulae of traditional Chinese medicine (FTCM), as the major component of traditional drugs, has played more important role on the prevention and cure to tumor. The Folkman's theory that tumorous growth depends on tumor neovascularization has been confirmed so many years, so to inhibit the tumor angiogenesis, is an important path to treat tumor. The research of FTCM to antagonizing tumor angiogenesis in our country has been started more lately. Since it has been reported some FTCMs can inhibit angiogenesis, and it also exists many problems. The article summarized the correlated research of FTCM to antagonize tumor angiogenesis for the past several years, and according this, analyzed, stated and commented to the problems, countermeasures, development and direction of PTCM to antagonize tumor angiogenesis.
Animals
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Chemistry, Pharmaceutical
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Drugs, Chinese Herbal
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therapeutic use
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Humans
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Medicine, Chinese Traditional
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Neoplasms
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drug therapy
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pathology
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prevention & control
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Neovascularization, Pathologic
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drug therapy
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prevention & control
3.Effects of shexiang baoxin pill on angiogenesis in atherosclerosis plaque and ischemic myocardium.
Wei SHEN ; Wei-hu FAN ; Hai-ming SHI
Chinese Journal of Integrated Traditional and Western Medicine 2010;30(12):1284-1287
OBJECTIVETo investigate the effects of Shexiang Baoxin Pill (SBP) in intervening atherosclerosis and myocardial infarction (AS-MI) in experimental animals, and inspect its influences on angiogenesis.
METHODSTwenty male New-Zealand rabbits were made into AS-MI model, and randomly divided into 2 groups equally. Group A was fed with high-fat diet for control; Group B was fed with high-fat diet but intervened with SBP. The cardiac function and the positive area of plaque were determined. The CD34 positive response intensity at infarcted marginal zone and aorta vessel wall, and the capillary density of myocardium were measured by immunohistochemical staining. In addition, the protein expressions of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) were detected by Western blot.
RESULTSCompared to Group A, the cardiac function was obviously improved (P<0.05) and the plaque positive area (%) was significantly decreased in Group B (45.82 +/- 3.68 vs 82.56 +/- 4.97, P<0.01). The CD34 positive response intensity and the capillary density as well as VEGF and VEGFR-2 expressions in infarcted marginal zone in Group A were higher than those in Group B (P<0.01); but these parameters at aorta vessel walls were lower in Group A than in Group B (P<0.01).
CONCLUSIONSBP could advance the angiogenesis in the marginal zone of infarction, improve heart function, and embarrass angiogenesis in atherosclerotic plaque.
Animals ; Atherosclerosis ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Myocardial Ischemia ; physiopathology ; Neovascularization, Pathologic ; physiopathology ; prevention & control ; Neovascularization, Physiologic ; drug effects ; Plaque, Atherosclerotic ; pathology ; physiopathology ; Rabbits ; Random Allocation ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism
4.Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis.
Tian-Min XU ; Man-Hua CUI ; Ying XIN ; Li-Ping GU ; Xin JIANG ; Man-Man SU ; Ding-Ding WANG ; Wen-Jia WANG
Chinese Medical Journal 2008;121(15):1394-1397
BACKGROUNDGinsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism.
METHODSThe experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells.
RESULTSIn the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.
CONCLUSIONSGinsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.
Animals ; Cell Line, Tumor ; Female ; Ginsenosides ; pharmacology ; Humans ; Lung Neoplasms ; prevention & control ; secondary ; Matrix Metalloproteinase 9 ; metabolism ; Mice ; Neoplasm Invasiveness ; Neovascularization, Pathologic ; prevention & control ; Ovarian Neoplasms ; drug therapy ; pathology
5.Acting mechanism of Cordyceps mycelia extract for antagonizing hepatic sinusoidal capillarization in rats with dimethylnitrosamine induced liver cirrhosis.
Xian-Bo WANG ; Ping LIU ; Zhi-Peng TANG
Chinese Journal of Integrated Traditional and Western Medicine 2009;29(9):810-815
OBJECTIVETo study the acting mechanism of Cordyceps mycelia extract (CME) for antagonizing hepatic sinusoidal capillarization (HSC) in rats with dimethylnitrosamine (DMN) induced liver cirrhosis.
METHODSRat liver cirrhosis model was established by peritoneal injection of DMN 10 mg/kg 3 times a week for 4 weeks. To rats in the CME-prevented group CME were administrated at a dose of 10 mL/kg, once a day, for 4 weeks. The observation time points were scheduled on the 3rd day (d3), and at the end of the 2nd (W2) and 4th week (W4) after modeling, and the following items were observed: hepatic ultrastructure was observed under electron microscope; expressions of CD44, von Willebrand factor (vWF) and type IV collagen (Col lV) in the liver sinusoidal walls by immunohistochemistry; matrix metalloproteinase-2 and-9 (MMP-2, MMP-9) activity under zymogram method; and serum hyaluronic acid (HA) content by radioimmunoassay.
RESULTSObservation at d3 showed MMP-2 and MMP-9 activity significantly increased, Col IV deposition and CD44 positive staining decreased, vWF positive staining increased in the liver sinusoidal walls, the fenestrae in the sinusoidal endothelial cells (SECs) decreased, and serum HA content increased (P<0.05); at W4, SECs defenestration and sub-SECs basal membrane formation were shown. In the CME-prevented group MMP-2 and MMP-9 activity significantly decreased (P<0.05); defenestration and basal membrane formation alleviated in the early stage (d3, W4); and at W2 and W4 decreases of HA content and vWF positive staining were shown, with increase of CD44 positive staining (P<0.05), more SECs fenestrae, and alleviated basal membrane formation.
CONCLUSIONSThe elevation of MMP-2 and MMP-9 activity in the early stage, which degrades the Col IV normally distributed under the sinusoidal endothelium, is an important factor for HSC formation. CME could inhibit the initiation of HSC by decreasing MMP-2 and MMP-9 activity in the early stage, and prevent its formation by decreasing SECs injury and phenotypic changes.
Animals ; Capillaries ; pathology ; Cordyceps ; Dimethylnitrosamine ; adverse effects ; Hepatic Veins ; cytology ; drug effects ; pathology ; Liver ; blood supply ; Liver Cirrhosis, Experimental ; pathology ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Mycelium ; Neovascularization, Pathologic ; prevention & control ; Rats ; Rats, Wistar
6.Thyroid hormone inhibits the growth of pancreatic cancer xenograft in nude mice.
Nan WANG ; Boxin SHANG ; Haitao SHI ; Hanwei MA ; Jiong JIANG ; Bin QIN ; Lei DONG
Journal of Southern Medical University 2013;33(8):1160-1164
OBJECTIVETo investigate the therapeutic effect of thyroid hormone in nude mice bearing human pancreatic cancer xenograft.
METHODSA BALB/c nude mouse model bearing pancreatic cancer was established with human pancreatic cancer cell line Bx-PC3. The mouse models were divided randomly into 5 groups, namely the control group treated with distilled water, high and low concentrations of thyroid hormone (T3) groups, and high and low concentration of propylthiouracil (PTU) groups. After intervention for 21 days, the changes in body weight and xenograft tumor volume and weight were measured, and the serum T3 concentration was detected by ELISA assay. The expression of proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were detected using immunohistochemistry.
RESULTSThe body weight of nude mice in T3 groups was significantly reduced after intervention, while that in PTU groups showed no obvious changes. Compared with PTU groups and control group, T3 groups showed significantly reduced tumor volume and weight (P<0.05) with also reduced PCNA expression and MVD, but these effect did not exhibit a dose dependence (P>0.05).
CONCLUSIONThyroid hormone can inhibit the growth of human pancreatic cancer in nude mice by suppressing the proliferation and angiogenesis of the tumor cells, suggesting the potential value of thyroid hormone in pancreatic cancer therapy.
Animals ; Cell Line, Tumor ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; pathology ; Neovascularization, Pathologic ; prevention & control ; Pancreatic Neoplasms ; blood supply ; pathology ; Proliferating Cell Nuclear Antigen ; metabolism ; Triiodothyronine ; pharmacology ; Xenograft Model Antitumor Assays
7.Antiangiogenic and antitumor effects of vascular endothelial growth factor small interfering RNA on Tca8113 human tongue squamous cell carcinoma xenografts in vivo.
Da-hai YU ; Jing LI ; Ying CAO ; Hai-bo CHEN ; Jie HAO
Chinese Journal of Stomatology 2008;43(9):556-560
OBJECTIVETo examine the antiangiogenic and antitumor effects of vector-based small interfering RNA (siRNA) targeting vascular endothelial growth factor (VEGF) on human tongue squamous cell carcinoma xenografts in vivo.
METHODSTca8113 human tongue cancer nude mice xenograft model was established, and subsequently divided into four groups randomly (5/group). Two siRNA targeting VEGF constructed in eukaryotic expression vector (PU-VEGF-siRNA1, PU-VEGF-siRNA2) were injected intratumor and peritumor with lipofectamine 2000, respectively. No siRNA vector injected and non-injected tumors were used as experimented and negative controlled, respectively. Animals were injected one time every 3 days for a total of 10 times. Three days after the last injection, the weigh and volume of tumors, and intratumor microvessel density (MVD) were measured. The expression of VEGF in xenograft tumors was detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry. The cell apoptosis and cell cycle analysis of tumors were detected by Tunel and Flow cytometry, respectively.
RESULTSCompared to the experimental and negative controls, the percentage of cells in the G(1) phase increased (P < 0.05), the expression of VEGF on both mRNA and protein level, the tumor weigh and volume, and MVD decreased in the PU-VEGF-siRNA2 group (P < 0.05), and more apoptosis was induced (P < 0.01). But significant differences were not noted between PU-VEGF-siRNA1 group and two controls (P > 0.05).
CONCLUSIONSVEGF-siRNA can reduce VEGF expression, inhibit tumor growth and angiogenesis, and induce apoptosis in Tca8113 cell carcinoma in vivo. Different VEGF-siRNA may have different effect in vivo.
Animals ; Apoptosis ; Carcinoma, Squamous Cell ; blood supply ; genetics ; pathology ; Cell Line, Tumor ; Humans ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic ; prevention & control ; RNA, Small Interfering ; Tongue Neoplasms ; blood supply ; genetics ; pathology ; Vascular Endothelial Growth Factor A ; genetics
8.Inhibitory effect of angiogenesis inhibitor TNP-470 on human ACHN renal cell carcinoma.
Jin ZENG ; Wei MEI ; Haipeng HUANG ; Xiaodong LI ; Peng KONG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(4):331-333
The contribution of angiogenesis inhibitor TNP-470 to the growth and metastasis of ACHN renal cell carcinoma (RCC) was studied. TNP-470 (40 mg/kg, every two days) was administrated to BABL/c nude mice bearing ACHN RCC. The mice were sacrificed after a treatment duration of 31 days and the weight and volume of subcutaneous tumors as well as foci of lung metastasis were measured. The microvascular density (MVD) of the tumor as well as the PCNA index and apoptotic index of the tumor cells were evaluated immunohistochemically. Result showed that the growth of ACHN RCC was suppressed significantly and none metastasis was observed in TNP-470-treated mice. Compared with the control group, the MVD was decreased markedly (P < 0.01) and the apoptotic index was increased significantly (P < 0.01) in the treated group. The tumor volume was positively correlated to the MVD (r = 0.7144, P < 0.01) and inversely correlated to the apoptotic index (r = -0.8607, P < 0.01), and MVD was conversely correlated to the apoptotic index. It was determined that TNP-470 could effectively inhibit angiogenesis of ACHN RCC, which resulting in ischemia and hypoxia, leading to increased apoptosis, thus obviously suppressing the growth and metastasis of ACHN RCC in nude mice.
Angiogenesis Inhibitors
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pharmacology
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Animals
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Apoptosis
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drug effects
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Carcinoma, Renal Cell
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drug therapy
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pathology
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secondary
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Cell Division
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Cyclohexanes
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Female
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Kidney Neoplasms
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drug therapy
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pathology
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neoplasm Transplantation
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Neovascularization, Pathologic
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prevention & control
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Random Allocation
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Sesquiterpenes
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pharmacology
9.Effect of Angiogenesis inhibitor (TNP-470) on the morphology of GNM cell line in vitro.
West China Journal of Stomatology 2002;20(3):175-177
OBJECTIVEThe purpose of this study was to investigate the effect of an angiogenesis inhibitor (TNP-470) on the ultra micro-structural morphological changes of GNM cell line, which was derived from human oral squamous cell carcinomas in vitro.
METHODSThe GNM cells were cultured and, the effect of TNP-470 on ultra micro-structural morphological changes of GNM cells was observed under the inverted microscope, the scanning electron microscope (SEM) and the transmission electron microscope (TEM).
RESULTSNumerous round cells, shrinkage of cellular membrane and dead cells were observed 48 hours after 2 micrograms/ml of TNP-470 was added into the GNM cellular suspension. After 72 hours, GNM cells became shortened and, the number of microvilli of the cellular surface was observed under the SEM and TEM. A large number of GNM cells turned into necrosis, accompanying with the destruction of mitochondria and endoplasmic reticula.
CONCLUSIONTNP-470 has a strong tumor cytotoxic effect on GNM cells, which may be due to its destructibility on mitochondria and endoplasmic reticula of GNM cells. TNP-470 can alter the surface structure of GNM cell membrane, which suggests that TNP-470 may interrupt the metastasis of GNM cells.
Angiogenesis Inhibitors ; pharmacology ; Antibiotics, Antineoplastic ; pharmacology ; Carcinoma, Squamous Cell ; blood supply ; pathology ; Cyclohexanes ; Gingival Neoplasms ; blood supply ; pathology ; Humans ; Lymphatic Metastasis ; Neovascularization, Pathologic ; prevention & control ; Sesquiterpenes ; pharmacology ; Tumor Cells, Cultured
10.Advances in the study of structural modifications of multi-target anticancer drug sorafenib.
Jian-Wen YAO ; Wei SUN ; Jing CHEN ; Wen-Fang XU
Acta Pharmaceutica Sinica 2012;47(9):1111-1119
Sorafenib, the first oral multikinase inhibitor, can inhibit several kinases involved in tumor proliferation and angiogenesis including Raf, VEGFR, PDGFR, kit and so on. Due to the advantages of multi-mechanisms, broad-spectrum anticancer potency, and well-tolerated results in combination trials, more and more researchers have focused on the optimization of sorafenib in order to develop novel multi-targeted anticancer drugs. The present paper reviews the development of modification of sorafenib in recent years from two aspects: bio-isosterism and scaffold hopping. The structure-activity relationship (SAR) of these compounds is also summarized.
Animals
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Antineoplastic Agents
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chemical synthesis
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chemistry
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Cell Line, Tumor
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Humans
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Molecular Structure
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Neoplasms
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drug therapy
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pathology
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Neovascularization, Pathologic
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prevention & control
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Niacinamide
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analogs & derivatives
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chemical synthesis
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chemistry
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Phenylurea Compounds
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chemical synthesis
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chemistry
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Protein Kinase Inhibitors
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chemical synthesis
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chemistry
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Structure-Activity Relationship