Saturday, November 3, 2012

Now a Word from the Creators: The Team who Designed and Synthesized the Molecule now called Ibrutinib

I was thrilled to the marrow to find the following email in my inbox.

I redacted two name as I do not yet have their permission to thank them personally.

I am hoping to talk to the team leader and post more on the history of the drug's birth and evolution. 

It takes more than a village to make a new drug and I am living in gratitude to so many, known and unknown.

Here's the first email (with very minor edits to protect identity):

Dear Dr. Koffman,

A former colleague just posted a link to your blog on his Facebook page. I'm happy to read of your positive response to ibrutinib.

Both of us were part of the team that discovered ibrutinib at Celera in 2005. One of my direct reports, Dr. X1, first designed and synthesized the molecule which we believed would be an inhibitor of Brutons Tyrosine Kinase (BTK). This enzyme plays a signaling role which we hypothesized is important in Rheumatoid Arthritis and cancer. Preclinical testing in animal models of RA and cancer cell culture looked very promising. Several months later, Celera shut down its pharmaceutical program and sold the rights to Pharmacyclics who subsequently advanced it into clinical trials.

My old team at Celera has since widely dispersed. Dr X1 is currently (teaching at a University in) China. Several others are no longer working in drug discovery due to massive lay-offs and changes in the US pharmaceutical industry. I am now with the National Cancer Institute and our former team leader (who posted the Facebook link) now works in Australia.

We are all thrilled to see that our molecule survived Celera's shutdown and has made it to the clinical setting. Words cannot express the joy we feel knowing that our work is positively impacting the lives of people like you. 

I hope for your continued recovery and will follow your blog with great interest.


Paul Grothaus, PhD
Bethesda, MD

Excepts from his follow-up email:

My former boss, Dr. X2, was the one who pointed me to your blog, he also told me that he had written to you as well. X2 was the one who coordinated the overall project and could best inform you about the drug's discovery and development at Celera. I was more directly involved in the chemistry rather than the biology of the compound. Of course, Pharmacyclics really deserves the credit for discovering its oncology applications and pushing it forward to the clinic. Development of any drug is really due to the work of many individuals, many of whom never really receive much credit or compensation. One doesn't go into this field expecting those, it's for the science and the hope that you find something useful. The dream of every medicinal chemist is to find a drug that makes it to the clinic and helps patients. We're all excited to have been part of that.

Best wishes for you and all cancer patients.


It is amazing to think that this molecule did not even exist in the universe until it was manmade only seven years ago, around the time that I was being diagnosed with CLL.

Like most breakthroughs, it began with a risky new idea and will only end with years of hard teamwork.

So many steps could have been missed. This molecule could have been less than a footnote to another company's shutdown and my story and that of so many others might be radically different and most likely less positive. Instead, through a path of fortuitous decisions, it is rapidly traveling forward to FDA approval for cancer treatment. I also hope I can learn more about from Pharmacyclics about how they moved the process on.

I am so lucky to have hitched a ride on part of this journey.

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Blogger Dr. La Verne said...

Dear Dr. Brian,

Please send my love and gratitude to the creators as well. I was 17p with no options.

-- Dr. La Verne

November 4, 2012 at 7:14 AM  

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