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1.
创新药物研发是国家医药产业发展的原动力,美国作为全球新药研发能力最强的国家,这与其食品药品管理局在新药审批过程中给
予的技术支持和政策鼓励密不可分。通过分析比较我国与美国的新药评审相关政策的异同,学习和借鉴美国的成功经验,为我国创新药物
注册审评制度的调整与完善提供参考。 相似文献
2.
Drug repositioning (also referred to as drug repurposing), the process of finding new uses of existing drugs, has been gaining popularity in recent years. The availability of several established clinical drug libraries and rapid advances in disease biology, genomics and bioinformatics has accelerated the pace of both activity-based and in silico drug repositioning. Drug repositioning has attracted particular attention from the communities engaged in anticancer drug discovery due to the combination of great demand for new anticancer drugs and the availability of a wide variety of cell- and target-based screening assays. With the successful clinical introduction of a number of non-cancer drugs for cancer treatment, drug repositioning now became a powerful alternative strategy to discover and develop novel anticancer drug candidates from the existing drug space. In this review, recent successful examples of drug repositioning for anticancer drug discovery from non-cancer drugs will be discussed. 相似文献
3.
由于具有优异的光学特性,量子点在生物医学领域内的研究和应用取得了一些有意义的进展,同时也引起了新药开发人员的兴趣.本文概述了量子点在新药开发中所具有的优势,分析了量子点在药物传输、药物筛选和药靶确证方面的潜在应用,进一步讨论了当前量子点应用于新药开发存在的问题和不足. 相似文献
4.
随着后基因组时代的到来,药物发现研究领域不断涌现出一系列新思路、新技术、新方法,从而迅速推进药物发现的多元化发展。一方面,基因组学、蛋白质组学、转录组学、代谢组学、生物信息学、系统生物学等新兴学科的崛起与发展,为药物发现提供更为广泛而深刻的理论基础;另一方面,计算机辅助药物设计、高通量筛选、高内涵筛选、生物芯片、转基因和RNA干扰等高新技术的发展和完善,为药物发现提供了新的技术手段和有力工具,极大地拓宽了药物发现的途径。本文结合近年来现代生物学的研究进展,综述现代生物学对药物发现过程的影响。 相似文献
5.
壳聚糖作为药物缓释控释载体的研究进展 总被引:4,自引:0,他引:4
壳聚糖因其具有良好的生物学特性而成为多种药物载体研究的热点。药物经过壳聚糖负载后,不仅能够达到缓释控释的目的,还能够改变药物的给药方式,以此减少给药次数,降低药物不良反应,提高药物生物利用度。本文就壳聚糖和改性壳聚糖作为普通药物和生物大分子药物载体的研究进展作一综述。 相似文献
6.
7.
Toll样受体(TLR)是一类模式识别受体,通过多种信号传递改善免疫系统功能,活化NF-κB信号通路,调节TNF-α、ILs和IFN-α等多种细胞因子分泌,在天然免疫系统中发挥重要作用,在免疫学及药物研究领域受到广泛关注。TLR种类众多,配体广泛,可以作为治疗微生物感染、炎症、自身免疫性疾病、 肿瘤及放射损伤等疾病的药物靶点,是免疫治疗的重要切入点。研究人员已经对数十种TLR靶向药物进行了研究。对TLR结构特征、信号传递以及靶向药物的特点和研究现状进行综述,分析其在免疫治疗方面的优劣势,也为下一步药物研究提供一定的理论依据。 相似文献
8.
2014年的新药批准和上市年终报告显示医药行业的活跃性持续保持在高位。截至2014年12月23日,共有55个新药和生物制
品首次上市。此外,29个重要的延伸性新药(新处方、新复方或已上市药物的新适应证)也在2014年首次上市。在这些新上市的药物中,
最多的是抗感染药物,有11个新药和生物制品。它们大多用于多药耐药菌引发的感染或丙肝的治疗。美国再一次成为这些新上市药物最青
睐的市场,该国是2014年半数以上新上市药物的首选地区。不过,日本在2014年开发上市新药的能力显著增强,多年来首次超越欧盟。
另一重要成果是:2014年上市的新药和生物制品中有15个获得罕见病用药资格,5个获得突破性治疗药物资格,还有3个获得合格传染
病产品(QIDP)资格。另外,2014年还有19个产品首度获批,将于2015年年初上市。 相似文献
9.
2014的新药批准和上市年终报告显示医药行业的活跃性持续保持在高位。截至2014年12月23日,共有55个新药和生物制品
首次上市。此外,29个重要的延伸性新药(新处方、新复方或已上市药物的新适应证)也在2014年上市。在这些新上市的药物中,最多
的是抗感染药物,有11个新药和生物制品。它们大多用于多药耐药菌引发的感染或丙肝的治疗。美国再一次成为这些新上市药物最青睐的
市场,该国是2014年半数以上新上市药物的首选地区。不过,日本在2014年开发上市新药的能力显著增强,多年来首次超越欧盟。另一
重要成果是:2014年上市的新药和生物制品中有15个获得罕见病用药资格,5个获得突破性治疗药物资格,以及3个获得合格传染病产
品(QIDP)资格。另外,2014年还有19个产品首度获批,将于2015年初上市。 相似文献
10.
2014的新药批准和上市年终报告显示医药行业的活跃性持续保持在高位。截至2014年12月23日,共有55个新药和生物制品
首次上市。此外,29个重要的延伸性新药(新处方、新复方或已上市药物的新适应证)也在2014年上市。在这些新上市的药物中,最多
的是抗感染药物,有11个新药和生物制品。它们大多用于多药耐药菌引发的感染或丙肝的治疗。美国再一次成为这些新上市药物最青睐的
市场,该国是2014年半数以上新上市药物的首选地区。不过,日本在2014年开发上市新药的能力显著增强,多年来首次超越欧盟。另一
重要成果是:2014年上市的新药和生物制品中有15个获得罕见病用药资格,5个获得突破性治疗药物资格,以及3个获得合格传染病产
品(QIDP)资格。另外,2014年还有19个产品首度获批,将于2015年初上市。 相似文献
11.
12.
The utility of primary human hepatocytes in the evaluation of drug-drug interactions is being investigated in our laboratories. Our initial approach was to investigate whether drug-drug interactions observed in humans in vivo could be reproduced in vitro using human hepatocytes. Two model drugs were studied: terfenadine and rifampin, representing compounds subjected to drug-drug interactions via inhibitory and induction mechanisms, respectively. Terfenadine was found to be metabolized by human hepatocytes to C-oxidation and N-dealkylation products as observed in humans in vivo. Metabolism by human hepatocytes was found to be inhibited by drugs which are known to be inhibitory in vivo, Ki values for the various inhibitors were derived from the in vitro metabolism data, resulting in the following ranking of inhibitory potency: For the inhibition of C-oxidation, ketoconazole > itraconazole > cyclosporin ~ troleandomycin > erythromycin > naringenin. For the inhibition of N-dealkylation, itraconazole ketoconazole > cyclosporin naringenin erythromycin troleandomycin. Rifampin induction of CYP3A, a known effect of rifampin in vivo, was also reproduced in primary human hepatocytes. Induction of CYP3A4, measured as testosterone 6-hydroxylation, was found to be dose-dependent, treatment duration-dependent, and reversible. The induction effect of rifampin was observed in hepatocytes isolated from all 7 human donors studied, with ages ranging from 1.7 to 78 years. To demonstrate that the rifampin-induction of testosterone 6-hydroxylation could be generalized to other CYP3A4 substrates, we evaluated the metabolism of another known substrate of CYP3A4, lidocaine. Dose-dependent induction of lidocaine metabolism by rifampin is observed. Our results suggest that primary human hepatocytes may be a useful experimental system for preclinical evaluation of drug-drug interaction potential during drug development, and as a tool to evaluate the mechanism of clinically observed drug-drug interactions. 相似文献
13.
目的 通过分析欧盟及其成员国的罕用药相关政策,为我国罕用药及罕见病相关制度政策的制定提供参考。方法 采用文献研究法对欧盟及其成员国法国、意大利、荷兰、英国的罕用药相关政策进行检索,并比较分析四国相关政策与制度的异同点。结果 除欧盟统一的罕用药政策外,法国、意大利、荷兰以及英国均制定了相应的罕用药制度,设立罕见病治疗指导中心,有针对罕用药研发与价格制定的政策与措施,对于罕见病的治疗有相应的医疗保障制度,相应的政策制度较为完善。 结论 我国可借鉴其经验尽快制定罕见病的相关定义,建立罕见病中心,出台相应的研发激励与价格制定政策,并完善罕用药的报销与罕见病的医疗保障。 相似文献
14.
Esmail K. Shubber David Jacobson-Kram Dr. Jerry R. Williams 《Cell biology and toxicology》1986,2(3):379-399
Seven antischistosomal drugs, two antimalarial drugs, and one antiamoebic drug were tested in all five Ames strains for induction of mutation, as well as for induction of cytotoxicity, inhibition of cellular progression, and the induction of sister chromatid exchanges in two cultured mammalian cell lines. We found that two agents shown to be negative in the Ames test were positive for sister chromatid exchange induction. Based on qualitative and quantitative evaluation, we find that all but three of the pharmaceuticals should be considered to be potential human carcinogens.Abbreviations AA
2-aminoanthracene
- 9AACC
9-aminoacridine
- AM
amoscanate
- BrdUU
bromodeoxyuridine
- CA
chloroquine diphosphate
- CHO
Chinese hamster ovary
- CQ
chloroquine
- DAPI
46-diamidino-2-phenylindole
- DHY
dehydroemetine
- DMSO
dimethyl sulfoxide
- EB
ethidium bromide
- FCS
fetal calf serum
- FN
4-fluoro-3-nitrophenyl azide
- HY
hycanthone
- ICP
inhibiting cell progression
- LU
lucanthone
- MEM
minimal essential medium
- 2NF
2-nitrofurantoin
- 4NPD
4-nitro-O-phenylenediamine
- NZ
niridazole
- OL
oltipraz
- OX
oxaminiquine
- PBS
phosphate buffered saline
- PQ
primaquine
- PZ
praziquantel
- SA
sodium azide
- SCE
sister chromatid exchange 相似文献
15.
目的
评价2007—2009年全国监测点医院的药物使用状况。方法 根据全国监测点医院的用药数据,采用金额分析和数据汇总的方法进行分析。结果 2007——2009年监测点医院的购药总金额呈现逐年上升的趋势,但各个省市的增长速度有所区别。抗感染药物、抗肿瘤药、心血管用药连续3年位列前3名。结论 随着医疗市场的扩大,药品消耗仍将在相当长的一段时期内持续增长,用药结构将发生变化。 相似文献
16.
Inferring potential drug indications, for either novel or approved drugs, is a key step in drug development. Previous computational methods in this domain have focused on either drug repositioning or matching drug and disease gene expression profiles. Here, we present a novel method for the large‐scale prediction of drug indications (PREDICT) that can handle both approved drugs and novel molecules. Our method is based on the observation that similar drugs are indicated for similar diseases, and utilizes multiple drug–drug and disease–disease similarity measures for the prediction task. On cross‐validation, it obtains high specificity and sensitivity (AUC=0.9) in predicting drug indications, surpassing existing methods. We validate our predictions by their overlap with drug indications that are currently under clinical trials, and by their agreement with tissue‐specific expression information on the drug targets. We further show that disease‐specific genetic signatures can be used to accurately predict drug indications for new diseases (AUC=0.92). This lays the computational foundation for future personalized drug treatments, where gene expression signatures from individual patients would replace the disease‐specific signatures. 相似文献
17.
Studies were conducted to examine the functional role of the nucleotide-binding domains of MRP in drug resistance and drug
transport in isolated membrane vesicles. In vivo studies were conducted by preparing stable transfectants of HeLa cells with
wild-type MRP cDNA or MRP cDNAs which had been mutated at certain nucleotide binding domains (NBD). Stable transfectants producing
equivalent amounts of the MRP encoded protein P190 were used in this study. The results demonstrated that deletions in the
C-motif of NBD1 or the A-motif of NBD2 have a pronounced effect in reducing resistance levels to chemotherapeutic agents.
Certain single-site mutations in lysines in these same motifs also reduce IC50 values. It has also been observed that mutation of the MRP NBDs results in an increase in drug accumulation and a reduction
in drug efflux. Additional studies have been carried out in which recombinant baculovirus containing either wild-type MRP
or MRP containing mutated NBDs was prepared and used to infect SF21 insect cells. Using this system we have analyzed the effects
of these mutations on in vitro transport of leukotriene C4 (LTC4) 17 β-estradiol 17 (β-D-glucuronide)(E217βG) and daunomycin in membrane vesicles prepared from baculovirus infected cells. The results demonstrate that deletions
and site-specific mutations in MRP NBDs greatly reduce the ATP dependent transport of all three substrates. The results of
these studies conducted both in vivo and in vitro demonstrate that the NBDs of MRP function in a cooperative manner and are
critical for the transport activity of the MRP encoded protein P190. These studies also identify specific lysines in NBD1
and NBD2 which are important for optimal MRP activity.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
18.
Pharmacogenetics is a field aimed at understanding the genetic contribution to inter-patient variability in drug efficacy and toxicity. Treatment of cardiovascular disease is, in most cases, guided by evidence from well-controlled clinical trials. Given the solid scientific basis for the treatment of most cardiovascular diseases, it is common for patients with a given disease to be treated in essentially the same manner. Thus, the clinical trials have been very informative about treating large groups of patients with a given disease, but are slightly less informative about the treatment of individual patients. Pharmacogenetics and pharmacogenomics have the potential of taking the information derived from large clinical trials and further refining it to select the drugs with the greatest likelihood for benefit, and least likelihood for harm, in individual patients, based on their genetic make-up. In this paper, the current literature on cardiovascular pharmacogenetics is emphasised, and how the use of pharmacogenetic/pharmacogenomic information may be particularly useful in the future in the treatment of cardiovascular diseases is also highlighted. 相似文献
19.
Molecular mechanisms and design principles for promiscuous inhibitors to avoid drug resistance: Lessons learned from HIV‐1 protease inhibition
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Molecular recognition is central to biology and ranges from highly selective to broadly promiscuous. The ability to modulate specificity at will is particularly important for drug development, and discovery of mechanisms contributing to binding specificity is crucial for our basic understanding of biology and for applications in health care. In this study, we used computational molecular design to create a large dataset of diverse small molecules with a range of binding specificities. We then performed structural, energetic, and statistical analysis on the dataset to study molecular mechanisms of achieving specificity goals. The work was done in the context of HIV‐1 protease inhibition and the molecular designs targeted a panel of wild‐type and drug‐resistant mutant HIV‐1 protease structures. The analysis focused on mechanisms for promiscuous binding to bind robustly even to resistance mutants. Broadly binding inhibitors tended to be smaller in size, more flexible in chemical structure, and more hydrophobic in nature compared to highly selective ones. Furthermore, structural and energetic analyses illustrated mechanisms by which flexible inhibitors achieved binding; we found ligand conformational adaptation near mutation sites and structural plasticity in targets through torsional flips of asymmetric functional groups to form alternative, compensatory packing interactions or hydrogen bonds. As no inhibitor bound to all variants, we designed small cocktails of inhibitors to do so and discovered that they often jointly covered the target set through mechanistic complementarity. Furthermore, using structural plasticity observed in experiments, and potentially in simulations, is suggested to be a viable means of designing adaptive inhibitors that are promiscuous binders. Proteins 2015; 83:351–372. © 2014 Wiley Periodicals, Inc. 相似文献
20.
全新结构药物的研发存在周期长、耗资大、风险高的问题.通过各种技术预测已有药物的新适应症,即药物重定位,可以缩短药物研发时间、降低研发成本和风险.由于疾病种类和已知药物的数量繁多,完全通过实验筛选已知药物的新用途仍然具有很高的成本.随着组学和药物信息学数据的积累,药物重定位进入到了理性设计和实验筛选相结合的阶段,药物重定位的计算预测已经成为计算生物学和系统生物学的重要研究方向.本文将目前药物重定位计算分析的策略归纳为药物-靶标关系分析、药物-药物关系分析和药物-疾病关系分析,对已报道的技术方法及其成功应用实例进行了综述. 相似文献