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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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July 25, 2013

Kevan Shokat At The Challenges in Chemical Biology Conference

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Posted by Derek

Kevan Shokat is now talking about his lab's work on using Drosophila models for kinase inhibitor discovery in oncology. I always like hearing about this sort of thing; very small living models have a lot of appeal for drug discovery.

You'd think that screening in fruit flies would be problematic for understanding human efficacy, but if you pick your targets carefully, you can get it to work. In Shokat's case, he's looking at a kinase called Ret, which is a target in thyroid cancer and is quite highly conserved across species. They set up a screen where active compounds would rescue a lethal phenotype (which gives you a nice high signal-to-noise), and screened about a thousand likely kinase inhibitor molecules.

Here's the paper that discusses much of what Shokat's group found. It turned out that Ret kinase inhibition alone was not the answer - closely related compounds with very similar Ret activity had totally different phenotypes in the flies. The key was realizing that some of them were hitting and missing other kinases in the pathways (specifically Raf and TOR) that could cancel out (or enhance) the effects. This was a very nice job of direct discovery of the right sort of kinase fingerprint needed for a desired effect. We need more tiny critters for screens like these.

Comments (6) + TrackBacks (0) | Category: Cancer | Chemical Biology


1. kinaguy on July 25, 2013 8:43 AM writes...

I assume you mean Kevan Shokat and not Brian, right?

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2. SP on July 25, 2013 8:48 AM writes...

I think he's talking about the love child of Kevan Shokat and Brian Shoichet. Professors at USCF do crazy things.

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3. Derek Lowe on July 25, 2013 9:20 AM writes...

Man, that's what comes out of trying to blog too quickly. Fixed!

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4. Brian Shoichet on July 25, 2013 9:21 AM writes...

Derek, on behalf of myself and my family, I'd like to thank you. Conversely, you may be hearing from Kevan's lawyers.

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5. isodope on July 25, 2013 1:24 PM writes...

Reminds me of a seminar a long time ago about brine shrimp used to assess toxicity. Plenty sensitive, easy to run and analyze, and nobody cares what you do to these little critters (except for maybe a couple of Jains). Not the industry standard so it went nowhere with us.

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6. under on July 25, 2013 8:16 PM writes...

It's the scaling down of the tablets that is the challenge!

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