KinasePro

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

PDB Update

Posted by kinasepro on January 16, 2007

Its been a slim last few weeks… Things are looking up though:

5 New Abl Xrays care of Novartis: 2HYY; 2HZ0; 2HZ4; 2HZI; 2HZN (medium-low rez and most have been published in one form or another…)

1 New “Vertex-Like” quinazoline bound to ‘STE-like kinase’: 2JAO


Is that an A-Loop in your pocket or are you just happy to see me?

 N#CC1=CC=C(NC2=NC(NC3=NNC(C4CC4)=C3)=C5C=CC=CC5=N2)C=C1

I consider these similar to VX-680.  The Takeda / BMS series likely hit Aurora quite the same.

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2 Responses to “PDB Update”

  1. Is the A-loop a regulatory unit? [unphosphorylated sitting over kinase pocket – phosphorylated swinging away to open up binding site?]

    What’s the general word on the street about Aurora inhibitors? Have been hearing many bad things about nasty tox problems….

  2. kinasepro said

    It’s the floppy looking thing on the right. When activated [or often even inactive (unphosphorylated)] it can adopt multiple conformations seeking the bliss of solvation, and thus be unresolved. That right up there is the biggest swing I remember seeing. At 2.3A is it real? Could just be a function of the crystal, but its interesting none-the-less.

    On Aurora… Well Merck is a go on Phii of VX680 (search MK-0457). It inhibits more then just aurora though, they claim it hits : flt3, Jak2, BCR-Abl, aurora a,b,c, and it probably hits more.

    Something like 80-90% of the people they’re planning to treat are going. to. die. though and have already failed gleevec, so I don’t have any illusions about what someone is willing to tolerate to make that not happen.

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