一夜一个鬼故事爆红的IDO抑制剂到底是什么鬼

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图书馆Special column【求解答】duang~到底是什么鬼【成都理工大学吧】_百度贴吧
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【求解答】duang~到底是什么鬼收藏
海运集装箱 锦江航运
感觉它一夜爆红
duang!duang!duang!好大的风
我的洗发水,一个视频,讽刺讽刺成龙大哥的
特效,找成龙
你们在说什么,我怎么什么都听不懂
还真的不晓得
欢迎加入全明星
趣现场-微信大屏幕 免费试用,现场30+互动功能,玩转现场!
b站又是什么东西?我感觉我对这个世界好陌生
什么。。啊
网友恶搞的成龙那个霸王防脱洗发露,和我的滑板鞋神同步。成龙大哥又继2014瓜子哥,百元妹,诸葛村妇王司猴之后,强势加入比站全明星阵容
终于明白了
顺便混个脸熟
一个寒假就out了,没听过  ★★★我有一群小鸭子,咿呀咿呀哟
duang~是特技的头发
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IDO抑制剂的研究进展
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IDO抑制剂的研究进展
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新型高效IDO抑制剂的筛选及在肿瘤治疗中的作用的研究.pdf 48页
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|JIIIIII I IIIIIII IIIIIllllI
摘要……………………………………………………………………………………1
Abstract….….….……………..………………。….…….…。.….…….………….….….….….……….….….2
前言………………………………………………………………………………………………………………..3日U舌………………………………………………………………………………………………………………..j
材料与仪器…………………………………………………………………………..11
1.材料与试剂……………………………………………………………………1l
2.实验仪器………………………………………………………………………12
实验方法……………………………………………………………………………..13
1.重组人IDO表达及纯化………………………………………………………13
2.rⅢD0生物活性测定…………………………………………………………..15
2.1rhIDO活性检测体系建立………………………………………………….15
2.2抑制类型测定………………………………………………………………16
2.3抑制剂Ki及Ic50值测定…………………………………………………16
2.4细胞水平IDO抑制活性测定……………………………………………..18
3.分子模拟对接…………………………………………………………………20
4.T细胞增殖反应……………………………………………………………..20
5.LLC肿瘤小鼠实验…………………………………………………………一2l
5.1Lewis肿瘤模型建立……………………………………………………….21
5.2实验分组……………………………………………………………………21
,5.3 IDO活性(Kyn/Trp)检测………………………………………………..21
5.4小鼠肿瘤组织中IDO与Foxp3的基因表达……………………………..21
5.5小鼠肿瘤组织中IDO与Foxp3的蛋白表达…………………………….23
5.6免疫组化检测IDO与Foxp3的表达情况………………………………..24
实验结果……………………………………………………………………………..26
1.rhIDO的表达与纯化…………………………………………………………26
2.IDO活性检测体系的建立…………………………………………………..26
3.HEK293细胞瞬转结果鉴定…………………………………………………27
4.IDO抑制剂的筛选…………………………………………………………..27
4.1CX系列IDO抑制活性的初筛……………………………………………27
4.2抑制类型判定及Ki、IC50的测定…………………………………………28
4.3CX系列细胞水平抑制效果……_………………………………………..29
5.分子模拟对接分析……………………………………………………………30
6.CX系列对T淋巴细胞增殖影响……………………………………………3
7.CX-47体内抗肿瘤作用………………………………………………………32
7.1CX-47对Lewis
正在加载中,请稍后...IDO抑制剂:Indoximod、NLG919、INCB024360
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IDO(吲哚胺2,3-双加氧酶)在部分恶性肿瘤中表达增强,通过分解色氨酸抑制T细胞激活介导免疫逃逸。目前处于临床实验阶段的IDO抑制剂有三个:NewLink Genetics公司的Indoximod和NLG919、Incyte公司的INCB024360。
INCB024360单药治疗转移恶性肿瘤一期临床实验中,52名患者中有15名病情稳定超过8周、8名病情稳定超过16周,没有患者部分缓解。
Indoximod在与多西他赛联用的转移性实体瘤一期临床试验中,可评估疗效的22名患者中4名部分缓解、9名病情稳定。
目前来看此靶点单药效果有限,还是要看与其他药物联用效果如何,尤其是CTLA-4/PD-1抑制剂。
请问针对什么癌的&
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共49条精彩回复,最后回复于 昨天&22:20
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有小分子药物吗?
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有小分子药物吗?
这3个都是小分子。
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这3个都是小分子。
那不错,有YL版的希望。
真想一觉醒来,我在小学教室对着小学同桌说:“我做了好长一个梦。”
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这类药物也可能和低剂量CTX(环磷酰胺)联合。低剂量CTX可以减少调节性T细胞数量,而增加T细胞数量,增强免疫力,同时还有抗血管生成作用。
真想一觉醒来,我在小学教室对着小学同桌说:“我做了好长一个梦。”
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不知道有人有兴趣试药吗,我对INCB024360很有兴趣
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IDO抑制剂,这个还很前期。他和自身免疫有关,也有文章说他参与了细胞周期的调控。但是有一点是比较确切的,他的单用药效不好。不然他也不会急着找Merck和BMS合作了。
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Bristol-Myers Squibb and Incyte Enter Clinical Collaboration Agreement to Evaluate Combination Regimen of Two Novel Immunotherapies
Phase I/II study to evaluate nivolumab, Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor with Incyte’s investigational oral IDO1 inhibitor for multiple cancers
NEW YORK & WILMINGTON, Del.--(BUSINESS WIRE)--May 27, 2014-- Bristol-Myers Squibb Company (NYSE: BMY) and Incyte Corporation (Nasdaq: INCY) announced today the establishment of a clinical trial collaboration to evaluate the safety, tolerability and preliminary efficacy of a combination regimen of Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, nivolumab, and Incyte’s oral indoleamine dioxygenase-1 (IDO1) inhibitor, INCB24360, in a Phase I/II study. Multiple tumor types will be explored in the study, which could potentially include melanoma, non-small cell lung (NSCLC), ovarian, colorectal (CRC), squamous cell carcinoma of the head and neck (SCCHN) and diffuse large B-cell lymphoma (DLBCL).
Nivolumab and INCB24360 are part of a new class of cancer treatments known as immunotherapies that are designed to harness the body’s own immune system in fighting cancer. Nivolumab and INCB24360 target distinct regulatory components of the immune system, and there is preclinical evidence suggesting that the combination of these two agents may lead to an enhanced anti-tumor immune response compared to either agent alone.
“Bristol-Myers Squibb is committed to pursuing the full potential of its immuno-oncology portfolio through the study of promising approaches to combination regimens,” stated Michael Giordano, senior vice president, Oncology and Immunosciences Development. “Given the encouraging data for Incyte’s IDO1 inhibitor and our current understanding of nivolumab’s anti-tumor immune response, we see this as an important area of study to add to our broad clinical development program.”
“The field of immunotherapy has the potential to transform the treatment of many cancers and significantly improve patient outcomes,” stated Hervé Hoppenot, President and Chief Executive Officer of Incyte. “Given the synergistic activity we have seen with our IDO1 inhibitor when combined with checkpoint inhibitors in preclinical models, and based on our emerging clinical data, we look forward to collaborating with Bristol-Myers Squibb to explore this combination across a wide range of tumor types.”
The study, which is expected to begin in the fourth quarter of 2014, will be co-funded by the companies and conducted by Incyte. Additional details of the collaboration were not disclosed.
About Nivolumab
Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Nivolumab is an investigational, fully-human PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. By blocking this pathway, nivolumab can enable the immune system to resume its ability to recognize, attack and destroy cancer cells.
Bristol-Myers Squibb has a broad, global development program in place to study nivolumab in multiple tumor types consisting of more than 35 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registrational trials in NSCLC, melanoma and renal cell carcinoma. In 2013, the FDA granted Fast Track designation for nivolumab in these three tumor types.
About INCB24360
INCB24360 is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays, potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity. INCB24360 has been shown to be efficacious in mouse models of cancer as a single agent and in combination with cytotoxic and immunotherapy agents, and its ability to reduce tumor growth is dependent on a functional immune system – consistent with its proposed mechanism of action. A Phase I dose-escalation trial demonstrated that INCB24360 results in greater than 90 percent inhibition of IDO1 activity at generally well-tolerated doses.
INCB24360 is currently in Phase I/II development for metastatic melanoma in combination with ipilimumab ( Identifier: NCT) and as monotherapy for ovarian cancer ( Identifier: NCT). Incyte has also established a clinical agreement with Merck to combine INCB24360 with Merck’s novel anti-PD-1 immunotherapy checkpoint inhibitor in a non-small cell lung cancer study.
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Indoleamine 2,3-dioxygenase and tumor-induced tolerance
David H. Munn1 and Andrew L. Mellor2
Tumors arise from normal cells of the body through genetic mutation. Although such genetic mutation often leads to the expression of abnormal antigens, the immune system fails to respond effective that is, it is tolerant of these antigens. This acquired state of tolerance must be overcome for cancer immunotherapy to succeed. Indoleamine 2,3-dioxygenase (IDO) is one molecular mechanism that contributes to tumor-induced tolerance. IDO helps create a tolerogenic milieu in the tumor and the tumor-draining lymph nodes, both by direct suppression of T cells and enhancement of local Treg-mediated immunosuppression. It can also function as an antagonist to other activators of antitumor immunity. Therefore, strategies to block IDO might enhance the effectiveness of tumor immunotherapy.
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Eosinophil Granulocytes Account for Indoleamine 2,3-Dioxygenase–Mediated Immune Escape in Human Non Small Cell Lung Cancer
Indoleamine 2,3-dioxygenase (IDO), a catabolizing enzyme of tryptophan, is supposed to play a role in tumor immune escape. Its expression in solid tumors has not yet been well elucidated: IDO can be expressed by the tumor cells themselves, or by ill-defined infiltrating cells, possibly depending on tumor type. We have investigated IDO expression in 25 cases of non small cell lung cancer (NSCLC). Using histochemistry and immunohistochemistry, we found that IDO was expressed not by tumor cells, but by normal cells infiltrating the peritumoral stroma. These cells were neither macrophages nor dendritic cells, and were identified as eosinophil granulocytes. The amount of IDO-positive eosinophils varied in different cases, ranging from a few cells to more than 50 per field at 200 magnification. IDO protein in NSCLC was enzymatically active. Therefore, at least in NSCLC cases displaying a large amount of these cells in the inflammatory infiltrate, IDO-positive eosinophils could exert an effective immunosuppressive action. On analyzing the 17 patients with adequate follow-up, a significant relationship was found between the amount of IDO-positive infiltrate and overall survival. This finding suggests that the degree of IDO-positive infiltrate could be a prognostic marker in NSCLC.
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