Kinase Chemistry – Just a year and a half behind the times.


Posted by kinasepro on June 3, 2009

aka Palladia, PHA-291639, & SU11654 got its FDA Approval today! Well… In dogs at least:.  It’s for canine mast cell tumors.

O=C(NCCN1CCCC1)C2=C(NC(/C=C3C(NC4=C\3C=C(C=C4)F)=O)=C2C)C yeh, its the pyrrolidine version of Sutent & its the phosphate salt

8 Responses to “Toceranib”

  1. Ryan K. said

    Makes me think that if I, or someone I knew was diagnosed with RCC or GIST, I’d buy the dog version over the $5000 28*25mg Sutent.

  2. taylor said

    It follows the european compound masitinib for the same application.

  3. milkshake said

    I would not recommend anyone Palladia for the unapproved human use. Sutent has already too long half-life of the active metabolites and it has a non-linear dose-response curve, and the tox profile is not very favorable (the safe dose is quite narrow, with QTc prolongation and organ accumulation-related toxicities seen in animal studies – adrenal necrosis and heart damage, among others problems) Sutent recommended therapy course has a treatment-free ‘holiday’ (like with conventional chemo) so that the patient can recover. Palladia is an analog that has even longer half-life in vivo, and most likely it is not any safer. The side-chain has actually a huge effect on the PK and toxicity profile. The improved safety profile clinical backup analog for Sutent was SU14813; it has a less basic 3-morpholino-2-hydroxy-1-propyl sidechain (and needs to be dosed somewhat higher and bi-daily).

  4. Ryan K. said

    That is very interesting… I kind of assumed that the pyrrolidine vs. diethylamine was merely for novelty (patentability) because the side chain is on the solvent exposed side. But now that I think about it, the side chain is also what tends to get metabolically chewed up first.

  5. Julia said

    I am curious that why Palladia is not suitable for human?

  6. Julia said

    If I want to know the history of Palladia,or I really want to know the reason why it is not suitable for human, where should I looking for these information?

    I am a student, it is one of my work to do…

    • milkshake said

      I don’t think you will find the history because the SUGEN company is long gone and the detailed account of the history was not published AFAIK. This work was done in a very small chemistry group (that did not even have its own NMR at the time) and they had to choose some simple side-chain. So they did dimethylamino, diethylamino, morpholino, pyrrolidino, piperazino etc and they looked at the potency vs toxicity and the half-life in animals.

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