Kinase Chemistry – Just a year and a half behind the times.

Archive for February, 2007

PDB Update

Posted by kinasepro on February 27, 2007

2J5E EGF w/ irreversible inhibitor
2J5F EGF w/ irreversible inhibitor
2HWP SRC (cystine mutant)
2HWO SRC (cystine mutant)O=C(C=C)NC1=CC(C(NC2=CC=CC=C2)=NC=N3)=C3C=C1

2JFL STE-20 like
2JFM STE-20 like

Posted in PDB | Leave a Comment »


Posted by kinasepro on February 26, 2007

Roche’s got a Vegf/FGF app in WO/2007/019884


They’ve been around since ’05 though

Posted in Fgf, Roche, VEGF | 1 Comment »

Who’s in CA?

Posted by kinasepro on February 26, 2007

No, not Canada, A? SF, CA – Here, have a sequal to the Prague entry: This is what you’re missing at YawnFest ’07, err I mean: the MMTC:

Wyeth talks Src/Abl: SKI-606 (American Cyanamid: WO/2000/018740)


Roche talks P38: R1487


And a former Abbot guy is talkinig LCK: A-770041


all great compounds and yadda yadda, just having a hard time seeing anything new here.

Posted in Abbott, bcr abl, Lck, p38, Roche, SRC, Wyeth | 4 Comments »

AP24534 In here?

Posted by kinasepro on February 25, 2007

Everyone looking at Abl these days is trying to wiggle their way around T315 and Ariad’s latest go is described in the app: WO/2007/021937 with a series of styrene-purines. They look to be a follow-on series to the earlier purine stuff described elsewhere.


Structures for their two previous SRC/ABL leads: AP23464 and AP23451 were disclosed but afaik AP24534 has not.

Posted in Ariad, bcr abl | Leave a Comment »

Beer Cures Cancer!

Posted by kinasepro on February 24, 2007

Sure the story‘s been around a while, but you know why we’re 18 months late covering it:

App is in a Metaproteomics‘ doublet: US20070042063 / WO/2007/021694


This has to be the best application KP has ever seen.


Posted in General Interest | 1 Comment »

The Thursday List

Posted by kinasepro on February 23, 2007

US20070043068 SGX Pharmaceuticals
US20070043065 p38 AstraZeneca
US20070043063 JAK Vertex
US20070043053 p38 BMS
US20070043048 IKK NOVARTIS
US20070043045 CDK-2 Schering-Plough
US20070043040 Akt Eli Lilly
US20070043010 EGFR AstraZeneca
US20070043009 EGFR AstraZene
US20070043001 AKT Merck
US20070042063 Metaproteomics

WO/2007/022529 Mek Array
WO/2007/022384 Aurora Vertex
WO/2007/022380 Lck / C-Kit AMGEN
WO/2007/022529 Mek1 Array
WO/2007/019884 Vegf / FGF Roche
WO/2007/019933 Met Merck DE
WO/2007/020388 Astrazeneca
WO/2007/020411 Astrazeneca
WO/2007/021710 P38 Merck
WO/2007/021795 Novartis
WO/2007/021694 Metaproteomics
WO/2007/022258 CDK2 Schering-Plough
WO/2007/022268 Novartis / Scripps
WO/2007/021937 Ariad
WO/2007/022241 CDK2 Schering-Plough
WO/2007/022102 Aurora Genentech / Roche
WO/2007/019884 Vegf / Fgf Roche

Posted in Application List | Leave a Comment »

What’s this I hear?

Posted by kinasepro on February 22, 2007

Is that the sweet sound of Kinase-Blogging Whistling in the Wind? Why yes, yes indeed it is.  (link to the original KP entry)

Read the rest of this entry »

Posted in General Interest, Wyeth | 3 Comments »

AZ’s got TrkA

Posted by kinasepro on February 22, 2007

I haven’t read it, but Cephalon’s got an Expert Opinion on the Array Biopharma / AstraZeneca’s Trk-A applications: WO06087538, WO06087530

OC[C@@H](C1=CC=C(F)C=C1)N2C=NC3=CC(Cl)=C(NC4=NNC(C5CC5)=C4)N=C32 C[C@@H](NC1=NC2=C(N=C([H])N2C3=NNC(C4CC4)=C3)C=N1)C5=CC=C(F)C=C5

In the series there’s also: WO/2006/082392


Cephalon’s got a staurosporine analog CEP-701 that hits the kinome, err I mean Vegfr-2, FLT-3, Trk-A and JAK-2 in ph3 trials for AML.

Bonus Link: Multi-Targeted Therapy = nice site.

Posted in Array, Astra, Trk | Leave a Comment »

Amgen ‘n’ IRAK-4

Posted by kinasepro on February 20, 2007

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. Read the rest of this entry »

Posted in Amgen, IRAK | 1 Comment »

The Vertex J Med Chem

Posted by kinasepro on February 18, 2007

TM brought it up… So here’s my two cents on the latest Vertex J Med Chem.

TM thinks the pyrrol – pyrazoles are ubiquitous, and Vertex says: ‘Kinase activity of pyrazolylpyrroles has been reported previously.16-18′

16:Vertex; WO/2001/057022
17:Vertex; WO/2003/011854
18:Vertex; WO/2003/011855

But refs 16-18 are the apps which cover this series and that’s about it for the 3 pyrroles. The 2-pyrrole substructure can be seen all over the place from things like the DNA/Roche aurora indoles, to chk1, to plenty of others. A subtle difference, but all the difference given how these hit the ERK hinge.

Anyhow, in going after the ERK gatekeeper with the pyrrole, it is surprising to find JNK3 activity since the JNK gatekeeper is methionine rather then glutamine. Interestingly the ligand adopts a flipped conformation in JNK3 more reminiscent of what you’d expect from the pyrrol-2-yl-pyrazole, like indoles, benzimidazoles and such.


The way the paper is worded it seems as though the selectivity was worked out in advance of the structures being obtained. Heh.  If nothing else, the PDB’s give a good example of a pyrrole tightly hydrogen bound to GLN. 2OJG, 2OJI, 2OJJ, 2OK1,

Posted in ERK, Vertex | Leave a Comment »