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

TPL2 4 Real?

Posted by kinasepro on November 27, 2006

Hey Wyeth, so is TPL2 for real? I see people have been talking up Cot/TPL2/MAP3K8 as another tnf-α inhibiting kinase target, but it seems that nobody else (cept maybe Abbott) seems to have jumped on board yet.

Yes that is a chloride atom there hugging the hinge.


Bioorg Med Chem Lett 2006, 6067
Bioorg Med Chem Lett 2005, 5288
(unrelated Abbott tpl2 series: WO2005110410)

ps. Thanks T.S. for the tip that wipo search feature bears much to be loved.


3 Responses to “TPL2 4 Real?”

  1. interesting target, although there is a strong sense of deja vu with these Wyeth quinoline nitriles (her2? aurora? or src?). That said you get deja vu all the time with kinases (glitch in the Matrix?)

    help out if you can?


  2. kinasepro said

    Yep, the cyano-quinoline is a known isostere of the quinazoline – The nitrile replaces the N-H2O interaction with the gatekeeper residue.

    The Ar-CN for Het-N isosteric replacement is a good one to get to know particularly if you suspect your pyridyl-like nitrogen is interacting through a water molecule.

    On the tech targets thing.. Well thats a good idea but, I’ve been on my share of interviews, and noone has ever asked me a technical chemistry type question. Weird huh?

  3. Top tip, ta very much. WRT technicals – you must just ooze knowledge….

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s

%d bloggers like this: