KinasePro

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

What did we miss in Prague?

Posted by kinasepro on November 12, 2006

Well c-Met must be the big-buzz-target these days as it seems to be the only kinase target talked about at EORTC. There were posters by: Exelixis, Arqule, Supergen, and Methylgene. Unless I’m missing something, none of these compounds have been partnered yet.


Exelixis: Ph1 data for 3 angio compounds: XL999, XL880, and XL184 (999 doesn’t hit met) Ex is fond of pointing out how they have the first c-met compound in the clinic with 880. Still have to dig up the patent app’s for 880, and 184. If the structures have been released please send me the smiles, otherwise I’ll dig through the patents and update as I get to it.

Arqule: ARQ 197 cute flash animation. Haven’t found the Poster yet… Only c-Met related patent app : WO2006086484

O=C(NC1=O)[C@](C2=CNC3=C2C=CC=C3)([H])[C@@]1([H])C4=CN5C6=C4C=CC=C6CCC5

Methylgene: (WO2006010264) Preclinical: c-Met VEGF Tie2 RON Poster doesn’t hit pdgfr-b.

c-Met PDB’s: 1ROP, 1R1W

Nerviano MS: Ok, so it wasn’t all met – there was also some phase one data on the Aurora kinase (a,b,c) inhibitor: PHA-739358.

O=C(NC1=C2C(CN(C([C@H](OC)C3=CC=CC=C3)=O)C2)=NN1)C4=CC=C(N5CCN(C)CC5)C=C4

>> Update >> previous structure for PHA-739358 was actually PHA-680632. Got the wrong one from scifinder, who in turn likely got it wrong from Keri’.

Bonus link: Oncology clinical stage drug candidates

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4 Responses to “What did we miss in Prague?”

  1. Did Nerviano give any indication if their Aurora candidate was orally available? Looks to me like it has a good chance of being so.

  2. kinasepro said

    Looks reasonable to me too, but in this trial it was delivered via infusion.

    http://www.medicalnewstoday.com/medicalnews.php?newsid=56441

  3. ebola1 said

    The structure of the most advanced Nerviano compound was shown in J Med Chem — (definitely an amide — the carbonyl is ver important in their series). The structure above is about as orally available as my foot — all data indicated that their treatment was not oral; however, I believe the best compound is.

  4. milkshake said

    Feet can have a good oral availability when formulated into a goulash, headcheese, blood sausages…. As they say in Prague: “Hunger is the greatest chef.”

    Nerviano realy likes these 2-aminopyrazoles – they have been doing them for years. When we were all part of Pharmacia we got from them this actual pyrrolo-pyrazole scaffold for derivatisation (they wanted SUGEN to do parallel synthesis for them) and according to my colleagues these Nerviano compounds were awfully polar but poorly soluble, regiochemistry was problem during derivatisation and the purification did not go too well either. There was no hope of developing it into deep-well plate parallel synthesis format that they wanted and the collaboration died eventually – I was spared of this work fortunately.

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