p*****m 发帖数: 7030 | 1 我理解你的意思 不过国内靠大分子药我觉得还是不靠谱 太贵了 用起来又不方便 1亿携
带者呢。。。国内还是要靠疫苗外加小分子药物。而小分子药物最直接的就是block病毒
entry.
当然了,你可以说乙肝携带者其实大多数的肝细胞都已经被侵染了 阻止entry用处不大
。但是现在乙肝在肝细胞之间怎么transfer的似乎了解的不是很清楚,也许阻止entry会
有意想不到的效果?(比如说,virus transfer对维持病毒的存在是关键的)
有没有人在做最针对这些个疑似receptor的药物,我也不是很清楚,只知道现在号称的
那些个receptor,没有一个是真正HBV specific甚至hepatocyte specific的,所以我
猜测这些不会是很好的target。PreS1 derived peptide作为entry inhibitor目前据说
效果已经非常好了,另有其他一些entry inhibitory peptide/molecule在pre-
clinical阶段的效果也不错,所以我估计眼下针对“疑似”receptor的rational
design不会有太大的吸引力... 阅读全帖 |
|
j****x 发帖数: 1704 | 2 entry inhibitor当然有价值,不仅对HBV了,HIV/HCV这些个老大难,如果是有效的
entry inhibitor,价值自然不菲。最近看到几个candidates,很BT的居然能光谱的同
时抑制多种病毒,太发指了。不过要说小分子药物,自然是NRTI和PI最简单,这在HIV/
HCV上体现的最明显。
HBV维持病毒的关键是核内cccDNA,类似HIV整合后的progenome(虽然cccDNA不整合
host genomic DNA),可以在肝细胞内长期稳定存在。小分子药物可以抑制病毒感染/
复制5年10年,但是只要还存在persistent form,病毒就有可能卷土重来。显然目前的
药物还无法直接清除。
亿携
病毒
entry会 |
|
j****x 发帖数: 1704 | 3 有没有人在做最针对这些个疑似receptor的药物,我也不是很清楚,只知道现在号称的
那些个receptor,没有一个是真正HBV specific甚至hepatocyte specific的,所以我
猜测这些不会是很好的target。PreS1 derived peptide作为entry inhibitor目前据说
效果已经非常好了,另有其他一些entry inhibitory peptide/molecule在pre-
clinical阶段的效果也不错,所以我估计眼下针对“疑似”receptor的rational
design不会有太大的吸引力。
chronic HBV治疗,要说最终解决还是得靠免疫学的方法,传统的NRTI也好,entry
inhibitor也罢,治标不治本,解决不了问题。强效Interferon以及前几天热炒的
Adoptive T cell therapy,我觉得应该是目前看来最有前景的方向吧,这玩意在国内
时市场太大了。
是了
用的 |
|
p*****m 发帖数: 7030 | 4 我理解你的意思 不过国内靠大分子药我觉得还是不靠谱 太贵了 用起来又不方便 1亿携
带者呢。。。国内还是要靠疫苗外加小分子药物。而小分子药物最直接的就是block病毒
entry.
当然了,你可以说乙肝携带者其实大多数的肝细胞都已经被侵染了 阻止entry用处不大
。但是现在乙肝在肝细胞之间怎么transfer的似乎了解的不是很清楚,也许阻止entry会
有意想不到的效果?(比如说,virus transfer对维持病毒的存在是关键的)
有没有人在做最针对这些个疑似receptor的药物,我也不是很清楚,只知道现在号称的
那些个receptor,没有一个是真正HBV specific甚至hepatocyte specific的,所以我
猜测这些不会是很好的target。PreS1 derived peptide作为entry inhibitor目前据说
效果已经非常好了,另有其他一些entry inhibitory peptide/molecule在pre-
clinical阶段的效果也不错,所以我估计眼下针对“疑似”receptor的rational
design不会有太大的吸引力... 阅读全帖 |
|
j****x 发帖数: 1704 | 5 entry inhibitor当然有价值,不仅对HBV了,HIV/HCV这些个老大难,如果是有效的
entry inhibitor,价值自然不菲。最近看到几个candidates,很BT的居然能光谱的同
时抑制多种病毒,太发指了。不过要说小分子药物,自然是NRTI和PI最简单,这在HIV/
HCV上体现的最明显。
HBV维持病毒的关键是核内cccDNA,类似HIV整合后的progenome(虽然cccDNA不整合
host genomic DNA),可以在肝细胞内长期稳定存在。小分子药物可以抑制病毒感染/
复制5年10年,但是只要还存在persistent form,病毒就有可能卷土重来。显然目前的
药物还无法直接清除。
亿携
病毒
entry会 |
|
c******r 发帖数: 3778 | 6 好像没有直接证据表明二者相关。
你上面说的间接关系是有可能的。就是说hypoxia导致肿瘤细胞migrate out of solid
tissue来获取养料,从而导致metastasis。但是这需要证据。最简单的,比如做个
migration assay,一边hypoxia,一边normaxia,然后看细胞是否向normaxia方向
migrate。当然这个实际操作上有些困难,最主要是现在的各种膜都是对oxygen自由通
透的。无法形成oxygen的梯度。
另外想办法的话,可以复杂点,直接做animal model。不是有VEGF inhibitor嘛。把肿
瘤细胞标记上luciferase之类的,然后打到老鼠里面。长到一定大小之后定期打
inhibitor,观察metastasis的差别。但是这也有技术问题。主要是现在的metastasis
没有特别好的model。皮下打的肿瘤,多数都不会自发地metastasis。所以可能需要做
些前期工作来找一个比较容易metastasis的cell line。 |
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g*********3 发帖数: 177 | 7 呵呵 有意思的对话。
其实这本来应该是个有意思的帖子,可能LZ没有表达他自己的意思吧。
最近看到了两篇关于cholesterol和cancer的关系,其中一篇是UCLA的,另一篇好像是
关于glioma的.
并且关于cancer的一些cholesterol inhibitor临床测试很早很早以前就有了,据说效
果还不错,但是那基本上称不上临床测试,只是系里某位很老很老的教授告诉我他们以
前做过类似的研究,但是最后因为经费中断没有继续下去。不知道现在有关于
cholesterol inhibitor治疗癌症的例子没有。
LS说的其实虽然...但是好像也是对的 哈哈
以前说是glucose对癌症关键,后来发现fatty acid对癌细胞也重要(Tak去年就有一篇
genes and development,并且据说那篇文章的结果很早就有了),现在又有了
cholesterol,不禁让我感到很失望,到最后我们不会发现真他妈连水也是关键的吧。
不过对于cholesterol,不只是作为component,有些蛋白比如ras的farnesylation也很
重要,并且我猜测(瞎猜的啊)chole... 阅读全帖 |
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s**********e 发帖数: 2888 | 8 其实NAC也不是specific inhibitor of ROS,它的生物活性非产的广泛,最好是用其他
结构的inhibitor一起去说明问题,比如catalase, sod enzyme |
|
f******g 发帖数: 1003 | 9 老板现在正在用chemical screening的方法筛选p21的inhibitor,已经有几个候选的了。
还在申请专利,把的前途说的神乎其神的。
我挺怀疑的,p53的inhibitor很早就有了,但是临床效果不是很明显。 |
|
s**********e 发帖数: 2888 | 10 举一个例子,Judah Folkman
早年他自己也做手术,后来自己开创了angiogenesis这个研究领域,现在做这个领域的人太多了,FDA批准了五六个angiogenesis inhibitor药物,最近新的angiogenesis inhibitor也有批准的。
http://www.time.com/time/nation/article/0,8599,1704028,00.html
"He would work 21 hours a day," says Brem. "He was chairman of pediatric surgery at Children's Hospital, so he would do surgery and see patients during day, then at night he would have dinner from six to eight, then work in the lab from eight to two a.m." That dedication led Folkman to change the way... 阅读全帖 |
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s******r 发帖数: 2876 | 11 folkman手术的功夫怎么样?
举一个例子,Judah Folkman
早年他自己也做手术,后来自己开创了angiogenesis这个研究领域,现在做这个领域的
人太多了,FDA批准了五六个angiogenesis inhibitor药物,最近新的angiogenesis
inhibitor也有批准的。
http://www.time.com/time/nation/article/0,8599,1704028,00.html
"He would work 21 hours a day," says Brem. "He was chairman of pediatric
surgery at Children's Hospital, so he would do surgery and see patients
during day, then at night he would have dinner from six to eight, then work
in the lab from eight to two a.m." That dedication led Folkma... 阅读全帖 |
|
i***0 发帖数: 160 | 12 that is what everybody want for misfolded protein diseases. According to my
knowledge, there is no compounds directly boosting proteasome function. But
you should thank me that I found during my digging for the unfolded protein
response and ER stress, the Hsp90 inhibitors induce transcription of
molecular chaperones and enhance proteasome activity. It is always easier to
find an inhibitor targeting an enzyme system, but difficult for activators.
I bet you will be reach, if you find a proteasome ... 阅读全帖 |
|
a*****x 发帖数: 901 | 13 首先要证明其可以被Ub修饰而不被proteasome降解。然后可以用E1 inhibitor,DUB
inhibitor,lysine mutants, cell fractionation and track the ubiquitnated
protein等等 |
|
m**b 发帖数: 617 | 14 NGS assisted personalized medicine in cancer therapy has already underway.
Here is one of the first clinical example published in 2010:
http://genomebiology.com/content/11/8/R82
Key points:
1) Rare cancer with no standard chemo therapy
2) Initial treatment with radiation therapy and EGFR inhibitor (patient had
high EGFR expression) failed to stabilize disease progression
3) DNA sequencing + RNA expression identified new potential drug target RET
4) Used RET inhibitor to treat patient (off-label ... 阅读全帖 |
|
m**b 发帖数: 617 | 15 NGS assisted personalized medicine in cancer therapy has already underway.
Here is one of the first clinical example published in 2010:
http://genomebiology.com/content/11/8/R82
Key points:
1) Rare cancer with no standard chemo therapy
2) Initial treatment with radiation therapy and EGFR inhibitor (patient had
high EGFR expression) failed to stabilize disease progression
3) DNA sequencing + RNA expression + pathway analysis identified genes in
known cancer pathways with CNV and expression chang... 阅读全帖 |
|
h******y 发帖数: 351 | 16 对于上皮细胞,最近有人发现利用feeder cells(主要是MEFs)和ROCK Inhibitor可以
有效immortalize。但是对于MEFs,光用ROCK Inhibitor可能不行。除了常用的SV40T和
HPV16 E6/E7,也可以用其他oncogene,例如c-Myc,Ras,BmiI,CDK4等等。因为MEFs
是原代细胞,转染效率很低,通常大家都用lenti,retro,或者电转。 |
|
j****x 发帖数: 1704 | 17 HBV PreS1前导肽是病毒受体的天然结合配体,这个很多年前就已经发现了,尽管一直
都不知道受体到底是什么。目前利用PreS1前导肽作用entry inhibitor的临床前实验基
本已经完成,已经进入Phase I阶段。我个人认为这个还是很可能有效果的,也是源自
乙肝病毒的特殊性,这里不细说了,呵呵,当然,本质上还是解决不了慢性感染cccDNA
长期存在的问题,只能作为联合治疗的其中一种方式。
另外,最近几年还发现了一系列广谱的entry inhibitor,非常有意思,所以说靶向受
体疗法今后成功的几率还是很低,呵呵,还真不好说呢
:(2)靶向病毒-受体的疗法还从没有成功过(当然也不能排除HBV会是个特例,但是几
: 率很小)。第一个例子是SDF和可溶性CD4都不能有效阻断HIV的感染。另一例子就是文
: 辉发现的SARS的受体ACE2,阻断ACE2达不到治疗的作用(当然也不排除有效的阻断
剂研
: 制出来前,SARS已经消失了)。 |
|
j****x 发帖数: 1704 | 18 HBV PreS1前导肽是病毒受体的天然结合配体,这个很多年前就已经发现了,尽管一直
都不知道受体到底是什么。目前利用PreS1前导肽作用entry inhibitor的临床前实验基
本已经完成,已经进入Phase I阶段。我个人认为这个还是很可能有效果的,也是源自
乙肝病毒的特殊性,这里不细说了,呵呵,当然,本质上还是解决不了慢性感染cccDNA
长期存在的问题,只能作为联合治疗的其中一种方式。
另外,最近几年还发现了一系列广谱的entry inhibitor,非常有意思,所以说靶向受
体疗法今后成功的几率还是很低,呵呵,还真不好说呢
:(2)靶向病毒-受体的疗法还从没有成功过(当然也不能排除HBV会是个特例,但是几
: 率很小)。第一个例子是SDF和可溶性CD4都不能有效阻断HIV的感染。另一例子就是文
: 辉发现的SARS的受体ACE2,阻断ACE2达不到治疗的作用(当然也不排除有效的阻断
剂研
: 制出来前,SARS已经消失了)。 |
|
s******y 发帖数: 28562 | 19 有啊。
Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11259-63.
Signal-induced degradation of I kappa B alpha requires site-specific
ubiquitination.
Scherer DC, Brockman JA, Chen Z, Maniatis T, Ballard DW.
Source
The inhibitor protein I kappa B alpha controls the nuclear import of the
transcription factor NF-kappa B. The inhibitory activity of I kappa B alpha
is regulated from the cytoplasmic compartment by signal-induced proteolysis.
Previous studies have shown that signal-dependent phosphorylation ... 阅读全帖 |
|
f******g 发帖数: 1003 | 20 某种组织中特意的用HSp inhibitor会如何,另外我觉得HSp inhibitor对衰老可能会有
影响 |
|
H*******g 发帖数: 321 | 21 确诊差不多快两年了,现在治疗在什么阶段?
除了年龄外,乳腺癌很重要的一个预后指标是雌激素/雄激素受体的状况。如果是阳性
的话一般预后比较好。
国内的治疗方案不熟悉。美国现在早期乳腺癌的生存率很高了。一般术后化疗或是放疗
,激素受体阳性的话还可以接着用tamoxifen或是aromatase inhibitors(后者只能用
于绝经妇女)。如果her2阳性的话,可以用herceptin或者叫trastuzumab。如果是激素
受体阴性的话,特别是her2也是阴性的话,目前没有什么好的target therapy。现在
parp inhibitors还在trial阶段,结果还不好说。 |
|
m******5 发帖数: 1383 | 22 Thank you !!!! for the ERK inhibitor, I supposed you were talking about 2i
medium? I thought I would need more than ERK, maybe also p38 inhibitor?
Could you coomment more on which part is the most tricky part?
Thank you very very much!
me
was
http://dev.biologists.org/content/137/20/3351.full.pdf
it |
|
C*******e 发帖数: 4348 | 23 “但是拿到基因组DNA上扩增就很差。 不同的底物浓度的ct值
很接近,而且都偏大”
——除了上面这么多id说的,
另外还有一个情况要注意,gDNA提取过程中很多时候会带有PCR inhibitor
有的是样品带来的(比如environmental sample可能含humic acids, polyphenols
),有的是提纯过程中引入的(比如EtOH去的不干净之类的)
所以不是模板越多就越该P出来的
很多时候稀释模板以后反而能够P出来就是这个道理
因为稀释的时候PCR inhibitor也被稀释了
你这个“不同第五浓度Ct值很接近,而且都偏大”可能就是这个因素 |
|
s*******2 发帖数: 598 | 24 See below 1997 paper
Biochem J. 1997 Apr 1;323 ( Pt 1):233-7.
Actin is cleaved during constitutive apoptosis.
Brown SB, Bailey K, Savill J.
SourceDivision of Renal and Inflammatory Disease, Department of Medicine,
University Hospital, Nottingham NG7 2UH, UK.
Abstract
Proteases play an important role in the programme of cell death by apoptosis
but little is known of the substrates cleaved, particularly in constitutive
models of this type of cell death. Neutrophils spontaneously undergo
apoptosis ... 阅读全帖 |
|
s*****g 发帖数: 7857 | 25 植物分离的天然产物的公司Sigma和印度的公司就已经做了.只是Sigma说是化学试剂而
已.到是印度的公司会告诉你这是提取的...另外还有
比如说Research [e*********[email protected]]就经常发些电子邮件广告:
关于新出来的Sunitinib
Dear Researcher,
We feel honored to introduce ourselves as one of the trading and sourcing
company based in India / China offering wide range of research chemicals and
biochemicals including novel life-science reagents, reference compounds and
Natural compounds for laboratory and scientific use. The volume of our
products
ranges from milligrams to kilograms scale. ... 阅读全帖 |
|
h****y 发帖数: 77 | 26 It's about aging. Any comment?
Turns out that the elusive Fountain of Youth may exist after all … in our
heads.
Scientists at the Albert Einstein School of Medicine say they’ve discovered
a brain region that may control aging throughout the entire body. By
manipulating that region, they were able to extend the lives of mice by 20
percent. The finding, detailed in a paper published in Nature on May 1, may
lead to new ways of warding off age-related diseases and increasing life
spans.
The hypothal... 阅读全帖 |
|
t**l 发帖数: 109 | 27 用5-azacytidine, ( DNMT inhibitor)处理细胞后,发现有些基因重新表达了,但是
DNA还是methylated.
相反,还有一个基因的DNA demehylated,但是却没有表达。怎么解释?
我感觉第二个情况好解释一点,因为还有其他的因素,比如polycomb? (求纠正)
但是第一种情况不太明白,之前是methylated的时候没表达,但是用DNMT inhibitor处
理之后,却表达了,但是DNA还保持着methylation 状态? |
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m******t 发帖数: 109 | 28 HDAC inhibitors, NAM+TSA needed in cell lysis buffer, except protease
inhibitor cocktail |
|
n**e 发帖数: 574 | 29 Merck Serono today announced that a global licensing, co-development and
commercialization agreement for BeiGene-290 has been signed with BeiGene Co.
, a biotech research and development company in Beijing, China. The compound
, which is a potent poly (ADP-ribose) polymerase (PARP) inhibitor for the
treatment of cancer, is currently in preclinical development and is expected
to enter clinical development next year. This is the second collaboration
agreement between the two companies this year.
P... 阅读全帖 |
|
h*******o 发帖数: 4884 | 30 in vitro or in vivo?
in vitro it is easy
You can use hexokinase inhibitor, such as 2-deoxyglucose,
You can use PDH activator, such as dicholoracetate
You can use Pyruvate transporter inhibitor, Thiazolidinediones
There are so many ways to manipulate cellular bioenergetic flux (glycolysis
or Mitochondrial OXPHOS), some may require digitonin or other similar
detergent to permeablize plasma membrane. |
|
h*******o 发帖数: 4884 | 31 2-DG can be considered as a suicide inhibitor of hexokinase, its
phosphoproduct by hexokinase, 2DG6P, inhibits hexokinase activity.
When dealing with metabolic flux, there is nothing that comes clean, that's
why such experiments need to be tightly controlled with multiple inhibitors/
reagents targeting different steps of metabolic pathway. |
|
p*****h 发帖数: 36 | 32 Suicide inhibitor is a term reserved for those capable of covalent
modification of enzyme active site. Of course at high concentrations, 2DG6P
as a substrate /product analogue inhibits several glycolytic enzymes
including HK and PFK.
It is for historical reasons that these drugs are dirty (phenotypic drug
screening came well before rational design). This is not to say there will
be no better drugs.
在 hellozero (hellozero) 的大作中提到: 】
s
inhibitors/ |
|
h*******o 发帖数: 4884 | 33 pigfish was right, 2-DG usually is not called as hexokinase inhibitor but
glycolytic inhibitor.
There are many other metabolic modulators that you can use, but keep in mind
, they often come with primary and secondary impact of metabolic flux and
you should tightly control your study so that the outcome can be interpreted
properly. |
|
S******e 发帖数: 393 | 34 将S1 (cytosolic protein) 和 S3 (nuclear soluble protein?) 去掉后,剩下的
pellet再用0.1%的Triton extract, 收集到的上清暂称为X,想知道X是些什么蛋白?
Chromatin associated protein?
方法如下:
1. Cells were extracted with Buffer A (10mM Hepes pH7.9, 10mM KCl, 1.5mM
MgCl2, 0.34mM Sucrose, 10% Glycerol, 1mM DTT plus protease inhibitors)
containing 0.1% Triton for 5 min on ice, centrifuge 1300g X5 min, discard
supernatant (S1), wash once with BufferA and discard supernatant.
2. Extract cell pellet with Buffer B (3mM EDTA, 0.2mM EGTA, 1mM... 阅读全帖 |
|
x*********n 发帖数: 43 | 35 做植物的,想用inhibitor处理植物抑制磷酸化(不是抑制磷酸化酶),请问有什么推
荐吗?
还有抑制mRNA降解的inhibitor有吗?
还有,抑制磷酸化酶的用roche的PhoSTOP行么?
问题有点多,谢谢 |
|
m******u 发帖数: 12400 | 36 问题不但有点多,还问得不清楚。
我也不懂,就知道“想用inhibitor处理植物抑制磷酸化”---有许多kinase抑制剂,但
不知你问得是不是kinase抑制剂。你如果你问的不是抑制蛋白磷酸化的,那我只有说不
知道了。
应该没有抑制mRNA降解的inhibitor,但有抑制RNase的东东叫RNasin,不知是不是你想
问的。 |
|
s*******n 发帖数: 37 | 37 你不能用phospho P38去检测p38 inhibitor,inhibitor 结合kinase domain,和
activation domain 的磷酸化是两回事。你应该用p38底物(mapkapk1?)的磷酸化去确
定抑制剂的效果。
activate
in |
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z*t 发帖数: 863 | 38 话说differentiation therapy从Waxmann提起有一段时间了,目前真正的
differentiation therapy还是俺们中国人搞出来的ATRA+As2O3。不知比埃尔霍夫最近
注意到agios这家公司没,他们针对IDH2 mutation的inhibitor跟ATRA效果类似。我看
好differentiation therapy在leukemia里的前景哈。化疗另外的问题是副作用,拿
leukemia来说,骨髓本来就是容易受化疗药影响,结果往往是病人丧失了正常的免疫能
力,只能通过输血维持,导致感染死亡的概率大大增加。
不过话说回来leukemia里头epigenetic factor mutation非常常见,epigentic相关
inhibitor能够induce differentiation不奇怪,这点跟solid tumor还是有很大区别 |
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d****i 发帖数: 2346 | 39 目前在做小肠组织的western,给RIPA buffer把SDS加到2%,然后sigma的protease
inhibitor cocktail加标准量的4倍(标准量是1:100稀释用的),但是每次lysate里面
都有蛋白降解。。。。。。。。所以想除了inhibitor cocktail还能加点啥瞬间灭火
protease还能用于western? |
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D**A 发帖数: 311 | 40 protease inhibitor 加够推荐的量就可以,多加浪费钱,效果还不一定好,可以加点
PMSF, benzamidine, EDTA之类的便宜inhibitor, 隔1-2小时补加一次就可。15%
glycerol.
先用液氮冷,然后快速解冻, 加冷的lysis buffer试试。
蛋白在室温下过夜会水解。
能想到的就这么多了。 |
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d****i 发帖数: 2346 | 41
非常感谢!我也是实在没办法,多加了inhibitor。PMSF也加了。
加了inhibitor的lysis buffer放在冰里遇冷,然后从液氮里拿出tissue,立即
homogenize。。。。
我说的室温过夜是加了6xloading buffer,另外我的buffer里还有2%的SDS,这样也会
降解吗? |
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y*******g 发帖数: 4 | 42 Postdoctoral Research Fellow Position in Institute of Glycomics, Griffith
University, Gold Coast, Australia
Prof Yaoqi Zhou’s group http://sparks-lab.org is built up a strong term for his molecular biology laboratory to interact with his computational laboratory at the Institute for Glycomics, Griffith University, Gold Coast, Australia. Initial exciting discovery in protein expression optimisation, antibiotic inhibitor discovery and protein design leads to the current expansion of the team. We... 阅读全帖 |
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r******k 发帖数: 446 | 43 LZ这个方法 难道直接往loading buffer里面加 protease inhibitor和 phospho
inhibitor? |
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A******y 发帖数: 2041 | 44 This just a guess. First, if you baseline OCR is okay, it is likely that
mouse ES cells are more resistant to the inhibitors. A lot of so call stem
cells have their efflux pump at maximum and just pump the inhibitors right
out. That's why they are so hard to kill. |
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g*****p 发帖数: 451 | 45 irreversible/mechanism-based inhibitor
inhibitor |
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A******y 发帖数: 2041 | 46 Hello, a phosphodiesterase inhibitor received FDA approval way before any
kinase inhibitor did in the 90s. The whole argument on the specificity of
kinase to be much better than phosphatase is simply lack of understanding of
their biology even today. |
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h*******o 发帖数: 4884 | 47 做AD的, 到目前为止 target abeta的尝试没有一个成功的 (不管是直接的abeta
vaccine, abeta 抗体, 还是beta secretase inhibitor, gamma secretase
inhibitor),包括前段时间(三月份)炒的沸沸扬扬的biogen的phase 1的 drug, 结
果到了7月份出来的新的trial data就股价暴跌了
gamma secretase inhibit的目前的最大问题是notch pathway的off target effect,
当然提高了gamma secretase的结构可能对于解决这个off target 问题有帮助,但是最
基本的问题还是, 减少了abeta 到底对于AD有没有clinical benefit
个人的感觉是现在industry 已经锁死在abeta这个target上面了,因为投入太多, 输
不起, 硬着头皮也要上
AD病人没效果的,就往MCI推, MCI效果还不明显,就要把therapeutic window更加提
前。
但是最大的问题是abeta hypothesis可能从一开始就... 阅读全帖 |
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T*****n 发帖数: 274 | 48 两种可能性都有吧。
原本就有的突变导致对药物的抗性,一个很典型的例子是在乳腺癌的PARP inhibitor治
疗中,如果这些细胞同时含有突变在抑制HR特别是resection的基因比如53BP1/Rev7等
基因上,会导致乳癌细胞对parp inhibitor产生耐受。
化疗同时也可能产生新的突变,如果这些新的突变带来selective advantage,那么他们
就有可能被carry on而导致癌细胞耐受。 |
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l****y 发帖数: 398 | 49 这玩意机理独特,和一般inhibitor还不一样
哈佛刚弄了个startup,要用类似的想法做ras,
[在 Barcv (比猪胖) 的大作中提到:]
:真是个好东西,specificity高,不像大多kinase/phosphotase inhibitor,non-
:specificity太高。
:真的很喜欢这个compound,像这样的化合物还有哪些? |
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