8 replies to this topic

[tiouki]

Hello all!

Some good news here, they have found some derivatives of sprycel that are effective in vitro, apparently even more effective.

Pierre

A link to the full text I have not read it yet http://www.sciencedi...960894X11017513  => quite short article, apparently some derivatives are at least twice as effective

And the abstract :

Bioorg Med Chem Lett. 2011 Dec 20.

Design, synthesis, and in vitro antiproliferative activity of novel Dasatinib derivatives.

Cai J, Zhang S, Zheng M, Wu X, Chen J, Ji M.

Source

School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China.

Abstract

Two series of novel Dasatinib derivatives have been designed and synthesized, with their in vitro cytostatic effect screened on human chronic myeloid leukemia cell line K562 and human myeloid leukemia cell line U937. Some target compounds demonstrated significant inhibitory activities against both cell lines. Compared to the contrast drug Dasatinib, 1b, 1c, 1d, 1e and 1f were found to demonstrate more potent antitumor activities. The structures of all the newly synthesized compounds were determined by (1)H NMR and (13)C NMR.

[Happycat]

Pierre,

These are a long way from turning into a drug.  BMCL is a journal for quickly publishing results.  It's not a journal for publishing rigorous studies.  Although interesting, it is also very early in the drug development pipeline, more like proof of concept.   These compounds have a long way to go, and could fail for various reasons along the way. 

However, it is great to see researchers working on It!  Even if these don't work out, someone will learn something which can lead to more advances.

Traci

[Trey]

I would be skeptical about anyone who says they have one drug that very efficiently fights both CML (K562) and Lymphoma (U937).  The side effects would likely be too significant.  Even sulphuric acid works in vitro against CML and Lymphoma cells, but....

[tiouki]

Hello here,

Yes I totally agree with both of you, it is very early, but the idea of finding derivatives from dasatinib is a nice plan for the 10 years to come I think (like if I remember Tasigna is derivated from gleevec). Of course they have to be tested in vivo, toxicity etc etc but maybe in 10 years or so new drugs will be on the market.

I don't know this journal so I can only trust you on that one.

Trey I agree and this is kind of surprising a priori, but I don't think that the derivatives from dasatinib have this kind of "bleach" effect or anything. Anyway it needs to be tested I guess (especially which kinases these molecules interact with and how strongly do they inhibit BCR-ABL in particular).

Anyway I am not too enthusiastic about this research but this gives me hope for new options in the decades to come

Pierre

EDIT : Trey another argument apparently even the "reference" dasatinib works against "lymphoma" model cell so these other molecules are not different regarding this, if you se what I mean.

[Happycat]

Pierre,

Here's a tip for you on journals. Generally, if you see "Letters" in the name, it means the editors accept papers with less rigorous standards. Letters are designed to publish the latest breaking results, so the researcher gets the credit for a new idea before getting scooped by someone else. (Competition can be fierce if it's a hot research area.)

In reality, researchers have to publish for the sake of their careers. This is especially true in academia. It is easier to get published in a Letters journal. Sometimes, Letters articles are really more resume-padding for the authors.

Traci

[tiouki]

Hey Traci, thanks for the info

Actually I am kind of a researcher myself (Not really yet as I will start my PhD soon ), but I am not used to all the subtleties of the literature yet so thanks for the tip!

Still, I thought this article seemed quite reliable. The principle is quite simple, just chemically change the molecule. And the tests, to measure the growth of leukemic model cells, are very basic but that's a good first step (especially for chemists )

Anyway we'll see I guess

Pierre

[Happycat]

Pierre,

What field will you study?  My PhD is in chemistry.

The method used here, optimize the activity and selectivity by tweaking a compound known to have the desired effect, is pretty standard for drug development.

It wouldn't surprise me to find that these derivatives are already covered in the parent patent for dasatinib.  When they write patents, they write them to cover just about every conceivable derivative and analog.

Traci

[tiouki]

Hey Traci,

It's a bit complicated I have a master in Biology, but not really specialized in a particular domain. I worked on neurosciences and cellular/molecular biology, but now I will probably do a PhD in Agricultural economics (basically it is multidisciplinary modelling).

What Chemistry do you do? Good luck with your PhD

Yes I guess it is pretty standard. And I see what you mean about the parent patents for dasatinib, but it is the first time I read something about them and it's quite interesting that some of them could actually work against our disease .

Pierre

[Happycat]

Pierre,

My part of the company offers drugs and drug like compounds to researchers for their research activities.  What we don't buy, we make in the lab.  Technically, I'm an organic chemist. The company was started by a professor to offer neuroscience research tools.  He got bought out by a bigger fish and now we offer research tools for all kinds of disease and biological studies. I got my PhD years ago, so now I just manage a group and try to keep product on the shelves.

Wow, from neuro to molecular bio to agricultural economics!  You are cutting a broad path through the sciences!  Good luck!  What school will you attend?

Traci