GSK’s got C-Met

WO/2008/049855 bears a certain resemblance to XL-184.

btw: XL-880 is now going by GSK-1363089

Gsk-690693

It’s an AKT inhibitor, and its been Terminated & Withdrawn… Wonder why.

Cancer Res, Blood, J Med Chem, Dartmouth?

GSK-690693

GSK’s AKT Alkynes?

Yah, you heard it here first. So Technically these are at least 3 years behind the times…

neener.

Some highlights…

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.

Pazopanib

aka GW-786034 is GSK’s ‘pan Vegfr’ inhibitor:

salt: hydrochloride
some chemistry here.
clinic: ph iii: RCC, WO/2002/05911

Pazopanib

aka GW-786034 is GSK’s ‘pan Vegfr’ / TIE2 inhibitor:

salt: hydrochloride
some chemistry here.
clinic: ph ii, WO/2002/059110

Tykerb ®

Tykerb ®, lapatinib, GW-572016

Discovery: Glaxo UK: WO/1999/35146
US Approval: March 2007

wiki; fda; PDB: 1XKK; Nature Reviews Drug Discovery

GSK and Ranbaxy in the P38 game

Earlier Ranbaxy had WO/2006/082492 and now its: WO/2007/036791. Add to that GSK has 2 oral P38 inhibitors in the clinic but despite some crafty wording of a recent Ranbaxy press release, the current clinical batch wasn’t an Indian invention. It looks as though GSK has shipped finding more backups overseas.

SB681323: Phii: COPD, Neuropathic pain
GW856553: Phii RA; RA; COPD;

One of them is likely from WO/2006/134382 (compound on the left) The other? Not so obvious. There’s a number of GSK p38 applications, but my guess is it hails from the pyrimidopyridone scaffold: Something like: WO/2003/088972 (above) or WO/2006/104915

Tykerb: a go

After announcement of the positive Ph3 it seemed like just a matter of time, and that time has come. Tykerb gets FDA approval in combination with Xeloda for treatement of advanced metatatic breast cancer where the cancer overexpresses Her2 as a second line therapy. And yes that is a mouthful… a 1.25g/d mouthful, worth eventually an estimated 1b/y.

GSK – More Aurora Active Pyrimidines

Here’s another Aurora application: WO/2007/018941

sensing a pattern?