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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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September 28, 2012

EMBL Chemical Biology: Progress in Oncology

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Posted by Derek

This evening's EMBL speaker is Paul Workman on new cancer targets and drug development. He's pointed out that treating cancer (and classifying cancer) by where it's located in the body is actually fairly primitive. Tumor cells in, say, breast cancer surely have more in common with various other type of tumor cells than they do with the normal cells surrounding them.

He claims that we're starting to see attrition rates come down in oncology, and I hope he's right. I see, though, that he's reified the "Valley of Death", which I'm not so sure about. There surely are some ideas in academia that should be moved along to development, but not all of them are worthy. (That's no slur - not all the targets inside the drug companies are worthy either, believe me). I worry that constant referral to a Valley of Death makes it sound as if there's something mysterious going on, when it really doesn't seem that strange to me. This Valley is mostly a gap between what works and what doesn't, rather than between academia and industry.

He also has a good slide on probe compounds versus drugs (here are the details). Probes, he says, need to meet even more stringent criteria for selectivity and potency than drugs do if their purpose is going to be to uncover new biology. Selectivity is usually the hardest barrier. That said, probes have to evolve. You don't find compounds like this right out of an HTS screen, and they're going to need some cycles of med-chem before they're truly ready for use. A less-than-optimal probe shouldn't be seen as a failure, but as an intermediate step.

Comments (7) + TrackBacks (0) | Category: Chemical Biology


1. barry on September 28, 2012 12:44 PM writes...

especially in oncology, clinicians are accustomed to high-clearance cmpds that must be given by infusion over hours. These cmpds allow them to tread closer to killing the patient and yet pull back in time. A probe compound against a novel cancer target could have ADME properties that many* would call disqualifying in a drug, yet--if it could invalidate the target for future work--save many millions of dollars and liberate researcher to work on other, more promising targets.

*who are committed to once-a-day oral drugs

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2. River on September 29, 2012 10:22 AM writes...

Is it time for Pharma to recognise the concept of "candidate" as a solely organisational artifact?
Surely better that we strive for "drug-quality probes" instead, which would encapsulate their true role even as they progressed into PIII and beyond.

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3. Morten G on September 30, 2012 7:29 AM writes...

Or maybe - I don't know - develop more than a single probe? And possibly learn something unexpected from these probes and also admitting that the selectivity screened for might not cover every single protein in the model?

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4. djm on September 30, 2012 8:29 AM writes...

What is the "Valley of Death"? I've not heard the term before.

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5. Andy on September 30, 2012 9:31 AM writes...

The "Valley of Death" is the disconnect between what Academia get funded to study and what actually works in the clinic. You often hear the phrase in relation to "Translational Science".

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6. simpl on October 1, 2012 2:52 AM writes...

Valley of Death' is the time gap between an idea for a treatment and its optimum implementation. I see it including the downhill gap between academia and product development, but also the uphill one until new drugs finds their niche. In oncology, there are now many ideas which are available, but not used fully, be it because of high costs or conservative treatment of serious conditions.

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7. Ed on October 1, 2012 7:30 AM writes...

With an annual research budget of over $500 million, Professor Workman's employers have more than sufficient resources to eliminate any Valley of Death.

They'd just rather someone else risked their dollars for the riskier parts of the job (clinical), so that the academics can keep their cosy gentlemens club unaffected and so they can keep on constructing or inhabiting ever flashier corporate buildings (brookes-lawley, Angel HQ, Francis Crick Institute)

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