AMG-900

It’s a Ph1 Aurora A/B/C inhibitor for ‘solid tumors’.  Seems likely to be a member of one of the phthalazine series’ WO/2008/124083, WO/2008/057280, WO/2007/100646, or WO/2007/087276.

previously…

Amgen: Us too.

As a comment in another thread notes, they have a handful of these too.  The regioismer is the novelty factor:

WO/2008/008539 / US2009012461 / 3CD8 / J Med Chem

AMG-458

Here’s one where they do tell us why its off the pipeline:

J Med Chem -> Chem Res Tox

Motesanib: A little too good.

Looks like this one might be coming off the ph3 list…

Motesanib‘s got “higher early mortality rates“

Amgen ‘n Aurora

WO/2007/087276? How ’bout that.

Motesanib

Motesanib diphosphate, AMG-706 hits: Vegfr1,2,3, c-kit, Pdgfr-b, and Ret

Salt: bisphosphonate
Clinic Ph iii: NSCLC
Cancer Res.; WO/2002/066470

Amgen all TIE2d up?

They describe Tie2 and LCK assays in a number of new apps, but it wouldn’t surprise me to learn a handful of other kinases were running in fear at the site of these things.

app is US20070054916

They’ve also got a C-Met application this week with US20070054903:

Amgen ‘n’ IRAK-4

Irak-4? Yah I never heard of it either, but the IRAKs appear to be immunology targets for which Amgen is way out in front. They’ve got a nice paper in Structure, a Biorg. Med. Chem. Lett., and 2 PDB’s: 2NRU, 2NRY.

At first look I was mesmerized by the tyrosine gatekeeper but a second glance on looking over the recent CIP: US20070037803 shows something interesting.

they suggest as much in the BMCL.

PDB Update

The highlight is GSK’s SB-590885 bound to B-Raf: 2FB8 (They describe the oxime as a phenol isostere)

Also, Amgen released the structurally interesting IRAK-4 bound to staurosporine (2NRY), and a benzimidazole inhibitor (2NRU). The Bioorg Med Chem Lett came out in March and the Xray is featured in this Structure paper.

The tyrosine gatekeeper is certainly different

Looks like there’s an indolinone lodged in today’s update as well. 2JAV replaces 2CL1, dunno why, probably some sort of refinement. NEK2 ne1?

AMG706

Update>> They named it: Motesanib diphosphate

Xcovery has the roundup on AMG706. I tend to think it’s a little apples and oranges to try and line it up against Sutent at this point. Heck it’s been nearly a year since release and noones come out and said Sutent is really any better then Nexavar.

The compound is second generation to ptk787; a VEGF inhibitor which failed to meet a Phase III endpoint.

There’s an article on the preclinical stuff: Cancer Research (2006), 66(17), 8715

Frankly KP is shocked that noone has yet published an application claiming the Bayer modification, woops scratch that, looks like Bayer has an application floating around: WO2006002383, but they don’t have the magic indoline.

ClC(C=C1)=CC=C1NC2=NN=C(C3=C2C=CC=C3)CC4=C=NC=C4 O=C(NC1=CC(NCC2(C)C)=C2C=C1)C(C=CC=N3)=C3NCC4=CC=NC=C4 O=C(C1=NC=CC(CNC2=CC=CC=C2C(NC3=CC=C(OC(F)(F)O4)C4=C3)=O)=C1)NC5CC5