PDB Update
Posted by kinasepro on November 6, 2007
c-Met + Indolinone: 2RFS; Amgen
c-Met + pyrimidone: 2RFN; Amgen <- Clearly the highlight of the day, but no image from me yet. I’m looking at it wondering where did all the polar contacts go? Peculiar structure, but noteworthy as the first published structure in the xl-880/kirin/bms/genentech/array/methylgene acyl urea isostere genre.
CDK2 + a pyrimidine macrocycle: 2J9M; chemmedchem; Schering AG
CK2: 2RKP: 1.56A
kinomics said
we see inhibitor binding to surface pockets quite frequently –
check out:
2CMW (CKg1) – same pocket – or
2BUJ (MPSK1) – nice packing of staurosporine –
don’t know if this is useful though –
by the way – SGC started to pre-release structures – this will save you 2/3 weeks time waiting for the pdb releasing the structure .. making Kinasepro even more up-to-date !
try:
http://www.sgc.ox.ac.uk
and have a preview at the latest kinase structure DMPK -
kinasepro said
Thats practically time travel… thanks!
oleg said
comment on c-Met 2RFS:
we have determined stk10 structure with the same inhibitor:
http://www.sgc.ox.ac.uk/structures/STK10A_2j7t.html
an it has a completely different orientation of Cl-phenyl ring !
kinasepro said
Indeed, hard to believe it’s already been a year, but we covered the release back then… Your group has been remarkably prolific!
In the header image of 11274 bound to c-met I tried to highlight the picturesque pi-stacking between said chlorophenyl ring and the adjacent Tyr-1230 residue.
milkshake said
The indolinone sulfonamide c-Met inhibitors had poor potency in cell. We got better activity with benzyl sulphone but the compounds were stil not druggable – they were quickly metabolized (at several postions in the molecule) and had a big problem with solubility, too. The later non-indolinone compounds were much better-behaved.