Posted by kinasepro on November 28, 2007
GSK’s been looking at Plk1 for quite a while. Sure the structure was in an earlier application (March), but here it is better late then never. See: WO/2004/074244, WO/2004/087652, WO/2005/019193, WO/2007/030361, US20070010668, & US20070270437
AP-24534 In here? Earlier Ariad had a double bond wiggling around T315I, in WO/2007/133560 & WO/2007/133562 it’s a triple bond.
And Vertex has an interesting series of series of Rock inhibitors in WO/2007/133622. Ki is reported to be <100 nM and clean across the cyps.
Oh yah, and if your curious about Cyclacel’s Aurora inhibitor CYC-116, they’ve narrowed it down to 1 of 3 for you and they also give an in vitro panel in WO/2007/132220, WO/2007/132221, WO/2007/132228. The claims make it look like the morpholine.
Posted in Ariad, bcr abl, Cyclacel, GSK, Plk1, Rho, Vertex | 4 Comments »
Posted by kinasepro on December 14, 2006
Hey Cyclacel, Good luck with the Aurora A+ B + Vegf + CDK + etc…. Phase 1. CYC116 IND submitted the other day, these compounds are likely from the thiazole-pyrimidine stuff.
Posted in Aurora, clinical, Cyclacel | Leave a Comment »
Posted by kinasepro on October 27, 2006
Hi again Cyclacel, Good idea to cover the pyridines too. Thanks for giving us the data. And hey, it appears you can walk around the activity wheel a little by varying the amine portion of the aminothiazole, but less then 10-fold over all the CDKs and GSK3 / Aurora? Unless your not showing us your ace, it makes Kinasepro wonder just how selective your PLK1 inhibitors are.
Posted in Aurora, CDK2, Cyclacel, GSK3 | Leave a Comment »
Posted by kinasepro on October 14, 2006
Yah we’re reaching back to last year, because it looks like you’ve patented an Xray (WO2005047526) but your webby still says all you’ve got is a model. The title of the app is: “Use of crystal structure of Plk1 kinase in screening for inhibitors…” So what gives? The app just has the coords of a model, but one would presume that was derived from a bona-fide xray. The models below shows the important Cys residue and calls it “C67”. Kinasepro likes how you dress up the application giving data on wartmannin (180 nM), staurosporine (800nM), purvalanol (5uM), LY2940002(9uM), and quercitin (65uM) Thanks for describing the docking of some various compounds. I notice you’ve done this kind of thing before with the CDK program. Good show. More interesting then your picture the ‘homology model’ is LANL’s stock model to the right. (could you xerox these things a few more times before sending them to the lawyer? Sheesh)
Even more better is the figure of adenosine, and thioadenosine, thanks for that.
I especially like your body of matter application (WO2005042525) and thoroughly guffawed at the title page xray complete with coordinates. That’s an xray of the compound, btw, not the complex… There really is no better way of saying:“THIS ISN’T HOW IT BINDS!” Thanks again for the heads up anyways, but lots of people including you have already shown that aminopyrimidines bind more like I’ve shown in D of the above figure. 1FPU is a good exception, but I don’t see that going on here. Of course as with some of the last posts, these are really just KP’s own educated guesses.
I’ll say this much anyhow: You’re thiazolones have KP wondering more and more about what’s going on with Schering’s stuff though.
Posted in Cyclacel, Plk1 | 1 Comment »