Off Targets

Just when you thought this stuff was easy… Turns out:

* Gleevec & Nilotinib hit ‘α-carbonic anhydrase‘ (wiki). (not to mention p38ß)

* Sorafenib hits P38 (new structure),

* GW-5074 (cRaf inhibitor) weakly hits glutamate dehydrogenase (~2uM, new structure, wiki).

Aurigene’s Insights

A Big thanks to Aurigene’s [colorblind] scientists who have been gracious enough to share with us this presentation given in India at a recent med-chem conference.

Structural Insights into Kinase Inhibition
More like this please!

Allosterism: A Diatribe

So just what is an allosteric kinase inhibitor?

@ AACR?

Send Structures / Will Post!

Email me smiles/inchi/chemdraw/iupac – whatever.  Structure and a corporate number is good enough, but any other info – feel free. (please include whether you want to be anon)

It’s all the rage

Kinase-Blogging is rightly where it’s at these day’s

MoTD: Got: Sutent?

Biohealth Investor: Got Sutent Too.

Derek: Wants to know if the field is still hot.

OPD: Still makin’em

Shaji: Has something to say

And Sammy read a paper (though has peculiar taste in music.)

to celebrate I’ll be hitting the post button a couple times over the next few days.

Rational design…

? ~ F(x) has some thoughts.

Ever since Captopril, I’ve always thought ‘rational design’ to be over-rated and over-sold.  We can do an awful lot without pin-point accuracy, and frankly we don’t have to understand why something is safe and effective to make it so.  Perhaps Ashutosh has tickled a nerve by bringing it up, but I fail to understand why people prefer this fanciful delusion of rational design to the reality of knowledge-based trial and error, but the primary literature is chock full-o-nuts claiming to be a lot smarter then they really are.  But I digress…

On non-oncology indications, of course Fasudil was approved in Japan in 1995 for ‘vascular spasms in the brain’ or some suchness, and is in Ph3 in the US for a few indications.  Pfizer and Incyte each have related Jak inhibitors which have looked promising in Ph2 studies.  Otherwise your looking at Rigel’s Ph2 Syk / Flt3 / Vegf inhibitor R-788 also in trials for RA but more likely to be approved for more acute indications, and then there’s always the p38 inhibitors, like Array’s recent ph2, but who knows if and when this target will deliver.

The fact that there was a Kinase-related conference and nobody could rattle that off suggests I’m not posting enough…

Boo!

CH——-Pi

Kissei’s done a little math on LCK ligands and suggests the stablization owes to those methyl’s.

BMCL

Cool, yah ,so, umm, like, thats why they gotta be flat.

UCB’s got a chart

go check it out.

Best of KP

In case you came late to the party, here’s some of my favorites:

The Kinaverse

Approved Kinase Inhibitors

Ph3 Kinase inhibitors

S—-O

Cl—-O

Note the RSS feed of my reading list.

Also note comments are closed – email me if you’ve got something to say, or start your own blog.  Go on – Its fun.