P*******e
发帖数: 27 | 1 After reading the comments about NIH, it seems to me people here has a
misunderstanding about the drug discovery process. People seem to believe
the drug discovery has always progressed like this: target---pathway---
cellular model---animal model---human beings. Indeed this is the well
publicized model or paradigm. But years ago, people used a phenotypic
screening to search for drugs without knowing targets, often directly on
animals. For anti-cancer drugs, many old ones were discovered without
knowing the MOA, including taxol. But with the advent of oncogenes, a more
reductionist approach as we all see today emerged. This approach indeed
discovered important anticancer drugs including the poster child of this
approach: gleevec. But we should remember CML is a simple and well defined
cancer in terms of genetic mutation. Bcr-abl mutation accounts for about 95%
of the cases, making it a perfect target. But for complex cancers such as
pancreatic cancer, there are many mutations (65?), the targeted approach
obviously is not working. That is why people in the drug discovery community
are advocating to going back to the traditional phenotypic screening at
least for complex diseases like cancer and other aging-related diseases. | b******k
发帖数: 2321 | 2 我也觉得忽略target直接根据表型做screen是个可以重新做起来的思路 但是你也不能
否认现在大多数药厂pipeline里的东西都是从target来的吧。。
【在 P*******e 的大作中提到】
: After reading the comments about NIH, it seems to me people here has a
: misunderstanding about the drug discovery process. People seem to believe
: the drug discovery has always progressed like this: target---pathway---
: cellular model---animal model---human beings. Indeed this is the well
: publicized model or paradigm. But years ago, people used a phenotypic
: screening to search for drugs without knowing targets, often directly on
: animals. For anti-cancer drugs, many old ones were discovered without
: knowing the MOA, including taxol. But with the advent of oncogenes, a more
: reductionist approach as we all see today emerged. This approach indeed
: discovered important anticancer drugs including the poster child of this
| S*********s
发帖数: 304 | 3 I agree. Old fashion phenotypic screen do bring us many chemodrugs(Ref: The
Story of Taxol).
But when toxicity comes, it is hard to eliminate it without knowing target
or potential targets.
With increasing analysis power of sequencing,metabolomics,and proteomics, in
the future we can evaluate toxicity of lead compounds using multi-Omics
approach and use that information to guide SAR optimization.
【在 P*******e 的大作中提到】
: After reading the comments about NIH, it seems to me people here has a
: misunderstanding about the drug discovery process. People seem to believe
: the drug discovery has always progressed like this: target---pathway---
: cellular model---animal model---human beings. Indeed this is the well
: publicized model or paradigm. But years ago, people used a phenotypic
: screening to search for drugs without knowing targets, often directly on
: animals. For anti-cancer drugs, many old ones were discovered without
: knowing the MOA, including taxol. But with the advent of oncogenes, a more
: reductionist approach as we all see today emerged. This approach indeed
: discovered important anticancer drugs including the poster child of this
| A******y
发帖数: 2041 | 4 NIH doesn't fund as much as pre-clinical translation science. There are two
study sections for pre-clincial drug discovery and both are worse scoring
ones of all study sections (i.e. you could still be top 40% with 6 in your
scores). | t*d
发帖数: 1290 | 5 It is not a misunderstanding. It is the best what we can do currently,
although it is far away from perfect.
All of us know the point, but none of us has a better solution.
【在 P*******e 的大作中提到】
: After reading the comments about NIH, it seems to me people here has a
: misunderstanding about the drug discovery process. People seem to believe
: the drug discovery has always progressed like this: target---pathway---
: cellular model---animal model---human beings. Indeed this is the well
: publicized model or paradigm. But years ago, people used a phenotypic
: screening to search for drugs without knowing targets, often directly on
: animals. For anti-cancer drugs, many old ones were discovered without
: knowing the MOA, including taxol. But with the advent of oncogenes, a more
: reductionist approach as we all see today emerged. This approach indeed
: discovered important anticancer drugs including the poster child of this
| M*P
发帖数: 6456 | 6 for complex cancer, I don't see a way of cure with simple drugs even when
you know all the targets.
【在 P*******e 的大作中提到】
: After reading the comments about NIH, it seems to me people here has a
: misunderstanding about the drug discovery process. People seem to believe
: the drug discovery has always progressed like this: target---pathway---
: cellular model---animal model---human beings. Indeed this is the well
: publicized model or paradigm. But years ago, people used a phenotypic
: screening to search for drugs without knowing targets, often directly on
: animals. For anti-cancer drugs, many old ones were discovered without
: knowing the MOA, including taxol. But with the advent of oncogenes, a more
: reductionist approach as we all see today emerged. This approach indeed
: discovered important anticancer drugs including the poster child of this
|
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