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


Posted by kinasepro on June 18, 2009

TAK-901 is Takeda’s ph1 Aurora B kinase inhibitor & US20090156557 suggests its:O=C(C1=C(C)C2=C(C(C3=CC=CC(S(=O)(CC)=O)=C3)=C1)C4=CC(C)=CN=C4N2)NC5CCN(C)CC5


7 Responses to “TAK-901”

  1. M. Blue said

    If it’s claimed to be an Aurora B inhibitor, does it mean it is highly selective over Aurora A or is Aurora A inhibition not that important?

  2. kinasepro said

    Supposedly Aurora A is the one you need… So an Aurora B selective inhibitor should allow a higher dose with lower tox.

    Takeda has not described the selectivity as far as I know. The patent application suggests ‘compound 88’ which I believe to be Tak-901 is 6-10 nM against B.

  3. AliG said

    I thought it still wasn’t clear which Aurora would be the better target. Inhibtion of each leads to different phenotypes in vitro (4N+ DNA for B, earlier block in M for A), but as far as a therapeutic window in vivo, I thought each have been shown to have efficacy, but only at doses very close to the doses that cause severe toxicity. I understand the Vertex/Merck AurB compound failed for non-mechanism reasons, so I don’t know when the first POC study will be complete for either one of these targets. Am I wrong? Can you dose AurB inhibitors well above the efficacious dose without tox?

  4. Moody Blue said

    Most of the “pan” Aurora inhibitors (like VX-680, which is actually somewhat more potent for AurA than B) induce phenotypes similar to Aurora B inhibition “only”. However, data using antisense oligos on pancreatic cancer cells have shown AuroA inhibitions is better target that AuroB. OTOH, RNAi studies using colon cancer cell lines showed that they were very sensitive to AuroB inhibition. And then there was a study showing inactivn of AuroB bypassing AuroA. AstraZeneca was touting their highly B selective compounds in few compounds. And Millenium’s AK inhibitor is highly A selective. These compounds and many others are still in trials, AFAIK. So I think the jury is still not out yet.

  5. Is this compound orally bioavailable?

  6. petros said

    Further reinforced by the cycl;odextrin formulation case WO2009107877

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