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971.
Jin M Kleinberg A Cooke A Gokhale PC Foreman K Dong H Siu KW Bittner MA Mulvihill KM Yao Y Landfair D O'Connor M Mak G Pachter JA Wild R Rosenfeld-Franklin M Ji Q Mulvihill MJ 《Bioorganic & medicinal chemistry letters》2011,21(4):1176-1180
Preclinical and emerging clinical evidence suggests that inhibiting insulin-like growth factor 1 receptor (IGF-1R) signaling may offer a promising therapeutic strategy for the treatment of several types of cancer. This Letter describes the medicinal chemistry effort towards a series of 8-amino-imidazo[1,5-a]pyrazine derived inhibitors of IGF-1R which features a substituted quinoline moiety at the C1 position and a cyclohexyl linking moiety at the C3 position. Lead optimization efforts which included the optimization of structure-activity relationships and drug metabolism and pharmacokinetic properties led to the identification of compound 9m, a potent, selective and orally bioavailable inhibitor of IGF-1R with in vivo efficacy in an IGF-driven mouse xenograft model. 相似文献
972.
Zhiguo WuYalong Liu Ji ZhangWeiliang Shen Wenxiang LuQing Hong Shunpeng Li 《International biodeterioration & biodegradation》2011,65(6):871-876
Strain D4 was isolated from the sludge of the wastewater treating system of a 4-Chloronitrobenzene (4-CNB) manufacturer. It was able to utilize 4-CNB as the sole carbon and nitrogen source for growth. Strain D4 was preliminarily identified as Cupriavidus sp. based on its physiological & biochemical characteristics and 16S rRNA gene sequence analysis. It could completely degrade 300 mg L−1 of 4-CNB within 25 h under the condition of 30 °C and pH 7.0. Strain D4 could also degrade 4-CNB in presence of heavy metals including Co2+, Cd2+, Pb2+, Zn2+, Mn2+and so on, therefore it was an excellent candidate for the bio-treatment of 4-CNB and heavy metals co-contaminated environments. The main 4-CNB degrading related genes (cnb A, B, Cab, D, G, Z) and arsenate resistance gene fragment of strain D4 were cloned, sequenced and analyzed, which showed high similarity with the corresponding genes of a reported 4-CNB-degrader, strain CNB-1. The cnb genes of strain D4 were located on two plasmids. This is the first report on the degradation of 4-CNB by the strain from the genus of Cupriavidus sp. 相似文献
973.
Lü S Luo Q Hao X Li X Ji L Zheng W Wang F 《Bioorganic & medicinal chemistry letters》2011,21(23):6964-6968
Six analogs of imatinib, an Abl kinase inhibitor clinically used as a first-line therapeutic agent for chronic myeloid leukaemia (CML), have been synthesized and characterized. And their potency as Abl kinase inhibitors have been screened by a robust virtual screening method developed based on the crystal structure (PDB code 2hyy) of Abl-imatinib complex using Surflex-Docking. The docking results are consistent with the inhibitory potency of the compounds characterized by MS method. And the H-bonds between imatinib analogs and Thr315 and Met318 residues in Abl kinase are shown to be crucial for achieving accurate poses and high binding affinities for the ATP-competitive kinase inhibitors. 相似文献
974.
975.
抗吡虫啉单克隆抗体的制备及鉴定 总被引:1,自引:0,他引:1
为制备灵敏度高,特异性强的抗吡虫啉单克隆抗体,建立经济、快速、准确的吡虫啉残留免疫学分析方法,采用分子模拟技术分析吡虫啉及其类似农药的电荷分布后,选择1-[6-(2-羧乙硫基-3-吡啶)甲基]-N-硝基-2-咪唑啉亚胺 (H1) 作为免疫半抗原,1-(6-氯-3-吡啶甲基)-3-羧丙基-N-硝基-2-咪唑啉亚胺 (H2) 作为包被半抗原,利用NHS酯法将H1和H2分别与牛血清蛋白 (BSA) 和卵清蛋白 (OVA) 偶联合成免疫原与包被原。免疫BALB/c小鼠后,采用常规杂交瘤技术共获得2株稳定分泌抗吡虫 相似文献
976.
NaCl胁迫下高纬度移植桐花树幼苗的生理生态效应 总被引:1,自引:0,他引:1
通过砂培试验,研究了不同浓度NaCl(0、100、200、300和400 mmol·L-1)处理对高纬度移植桐花树幼苗生物量、离子吸收、碳氮代谢、叶片光合色素和叶片抗氧化系统的影响.结果表明:100 mmol·L-1NaCl处理对桐花树生长有轻微的促进作用,当NaCl浓度达到300mmol·L-1时,桐花树根、茎、叶器官的干鲜质量、根冠比、株高和基径均显著下降.高盐胁迫抑制了叶片抗氧化系统中超氧化物歧化酶(SOD)和过氧化物酶(POD)的活性,提高了丙二醛含量,降低了叶片中叶绿素、类胡萝卜素总量以及根茎叶的可溶性总糖和游离氨基酸总量.不同浓度NaCl胁迫下,桐花树根茎叶中Na+含量快速上升,K+含量相对下降,K+/Na+快速下降,导致各器官中离子平衡失调.当NaCl浓度高于300 mmol·L-1时,桐花树根茎叶的碳氮代谢运转失调,抑制了植株的正常生长,导致各器官的生物量显著下降. 相似文献
977.
目的 建立呼肠孤病毒Ⅲ型(Reo3)免疫荧光(IFA)检测方法,应用于人用动物源性生物材料及生物制品外源Reo3的检测。方法滴定病毒TCID50,筛选Reo3敏感细胞,依据国标IFA法制备抗原片,方阵法滴定免疫荧光素最佳工作浓度。并进行特异性、敏感性和稳定性试验。结果选取BSC-1细胞作为Reo3敏感细胞,病毒感染力滴度(TCID50)为10-5.8/mL;免疫荧光素最佳工作浓度为1∶100;与小鼠鼠痘(Ect)病毒、小鼠肝炎(MHV)病毒均无交叉反应;稳定性和敏感性试验显示,不同时间IFA检测灵敏度均为1∶1280;可检测到的病毒滴度最低为10-4.1/mL。结论建立的IFA法敏感性、特异性强,稳定性好,可用于人用动物源性生物材料及生物制品Reo3的检测。 相似文献
978.
Choi JM Chu SJ Ahn KH Kim SK Ji JE Won JH Kim HC Back MJ Kim DK 《Molecules and cells》2011,32(4):325-331
Ceramide has been suggested to be not only a tumorsuppressive lipid but also a regulator of phagocytosis. We examined whether
exogenous cell-permeable C6-ceramide enhances the phagocytic activity of Kupffer cells (KCs) and affects the level of cellular ceramides. Rat KCs were
isolated by collagenase digestion and differential centrifugation, using Percoll system. Phagocytic activity was measured
by FACS analysis after incubating KCs with fluorescence-conjugated latex beads, and the level of cellular ceramide was analyzed
by liquid chromatography tandem-mass spectrometry (LC-MS/MS). In this study we found that permeable C6-ceramide increases the cellular levels of endogenous ceramides via a sphingosine-recycling pathway leading to enhanced phagocytosis
by KCs. 相似文献
979.
Wogonin is a one of the bioactive compounds of Scutellaria baicalensi Georgi which has been shown to have antiinflammatory, anticancer, antiviral and neuroprotective effects. However, the underlying
mechanisms by which wogonin induces apoptosis in cancer cells still remain speculative. Here we investigated the potential
activation of MAPKs and generation of reactive oxygen species (ROS) by wogonin on MCF-7 human breast cancer cells. These results
showed that wogonin induced mitochondria and death-receptor-mediated apoptotic cell death, which was characterized by activation
of several caspases, induction of PARP cleavage, change of antiapoptotic/proapoptotic Bcl-2 family member ratios and cleavage
of Bid. We also found that generation of ROS was an important mediator in wogonin-induced apoptosis. Further investigation
revealed that wogonin activated ERK and p38 MAPKs, which was inhibited by N-acetyl cysteine (NAC), a ROS scavenger, indicating
that wogonin-induced ROS are associated with MAPKs activation. These data demonstrate that wogonin may be a novel anticancer
agent for treatment of breast cancer. 相似文献
980.
A moderate change in ambient temperature significantly affects plant physiology including flowering time. MiR399 and its target
gene PHOSPHATE 2 (PHO2) are known to play a role in the maintenance of phosphate homeostasis. However, the regulation of flowering time by the miR399-PHO2 module has not been investigated. As we have previously identified miR399 as an ambient temperature-responsive miRNA, we
further investigated whether a change in expression of the miR399-PHO2 module affects flowering time in response to ambient temperature changes. Here, we showed that miR399b-overexpressing plants
and a loss-of-function allele of PHO2 (pho2) exhibited an early flowering phenotype only at normal temperature (23°C). Interestingly, their flowering time at lower temperature
(16°C) was similar to that of wild-type plants, suggesting that alteration in flowering time by miR399 and its target PHO2 was seen only at normal temperature (23°C). Flowering time ratio (16°C/23°C) revealed that miR399b-overexpressing plants
and pho2 mutants showed increased sensitivity to ambient temperature changes. Expression analysis indicated that expression of TWIN SISTER OF FT (TSF) was increased in miR399b-overexpressing plants and pho2 mutants at 23°C, suggesting that their early flowering phenotype
is associated with TSF upregulation. Taken together, our results suggest that miR399, an ambient temperature-responsive miRNA,
plays a role in ambient temperature-responsive flowering in Arabidopsis. 相似文献