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

Archive for October, 2007

PDB Update

Posted by kinasepro on October 30, 2007

Merck (WP) Chk1, 2R0U: BMCL

6-(3-aminopropyl)-4-(3-hydroxyphenyl)-9-(1H- pyrazol-4-yl)benzo[h]isoquinolin-1(2H)-one

Posted in Chk1, Merck & Co., PDB | 6 Comments »


Posted by kinasepro on October 30, 2007

Posted in General Interest | 2 Comments »

Tasigna Approved

Posted by kinasepro on October 30, 2007

aka nilotinib, AMN-107 is a Novartis‘ follow-on to Gleevec now approved for CML.


wiki; clinic; WO/2002/022597

Posted in Approved, bcr abl, gleevec, Novartis | 4 Comments »


Posted by kinasepro on October 27, 2007

Celgene S.D. aka Signal has a series of v600e active thienopyrimidines that also appear to hit the non-kinase PDE4.



(NH2 > S)

Posted in Celgene, RAF | Leave a Comment »


Posted by kinasepro on October 27, 2007

Buy this compound?


From: WO/2006/010127 and recently described as inhibiting PKC.

Go ahead, laugh it up – but hey, it could always be worse:

Posted in biotech | 20 Comments »

Selective vs. Nonselective

Posted by kinasepro on October 25, 2007

There are a handful of ways to visualize selectivity among kinase inhibitors after you’ve had them Profiled.

The gold standard has become the Ambit panel:


(from the Nature Biotech paper)

A simple chart will get the job done:

(INNO-406 / NS-187, from Blood 05, 3948)

or a heat map like Amphoras’:

If you prefer a reductionist approach you’ve always been able to take it down to a single number with fold shift from its nearest neighbor.

And now it looks like there may be a statistically more meaningful number with the recent J Med Chem on applying the Gini Coefficient to kinase inhibitor selectivty. In case you missed it, check out the spreadsheet in the supporting info.

Posted in General Interest | 6 Comments »

PDB Update

Posted by kinasepro on October 24, 2007

2O5K, GSK3, 3.2A, CrystalGenomics: BMCL (re-refine phenol plz)

2REI, Epha7, 1.6A, SGC

2QVS, PKA, 2.5A, UCSD: Science:

Posted in PDB | 3 Comments »


Posted by kinasepro on October 22, 2007

Abstracts are up, and B is the one you’ll be looking for.

News of the day:

In pts [patients] with PRC, XL-880 demonstrated antitumor activity

Name Target Company Phase
AZD-2171 Vegf c-Kit Pdgfr-β AstraZeneca ph2
AZD-2171 Vegf c-Kit Pdgfr-β AstraZeneca ph2
PD-325901 Mek Pfizer ph2
XL-647 ErbB1,2 Vegfr-2 Exelixis ph2
XL-880 c-Met Vegf Exelixis ph2
ARQ-197 c-Met Arqule ph1
BAY-579352 Vegfr-2,3 c-Kit Pdgfr-β Bayer ph1
BAY-734506 c-Kit Ret Pdgfr Raf Bayer ph1
BIBW-2992 ErbB (irrev) BI ph1
PD-325901 Mek Pfizer ph1
PF-299804 ErbB (irrev) Pfizer ph1
Ticribine Akt VioQuest ph1
XL-647 ErbB 1,2 Vegfr-2 Exelixis ph1
XL-820 Vegfr c-Kit Pdgfr Exelixis ph1
XL-880 c-Met Vegf Exelixis ph1
ARRY-543 ErbB1, 2 Array ph1
AT-13148 Akt Rock PKA Astex  
AV-951 Vegf Aveo ph1
BAY-734506 c-Kit Ret Pdgfr Raf Bayer  
BMS-698769 c-Met BMS  
CEP-11981 Tie2 Vegfr Cephalon  
CUDC-101 HDAC / ErbB Curis  
NVP-BEZ235 Pi3k Novartis  
OSI-906 IGF-1R Osi  
RDEA-119 Mek Ardea  
SGX-523 c-Met SGX  
SR-13654 Src SRI  
XL-765 Pi3k, mTOR Exelixis  
XL-820 c-Kit Exelixis  
XL-844 Chk1, 2 Exelixis  
ZD-6474 Vegfr-2 EGFR    
ZM 447439 Aurora    
CRT-59359 PKD CRT  

Duplicates and phase field just reflect the subject of the poster / reported trial, click for more details.

Posted in clinical | 1 Comment »

Weekend Reading

Posted by kinasepro on October 19, 2007

Imagine that, a Chem Rev I’m actually going to read?

Posted in General Interest | 2 Comments »

Cl – – – – O

Posted by kinasepro on October 18, 2007

I am somewhere between faithless and agnostic on the role of through space ‘halogon bonding’, but earlier a reader pointed us towards a review on the subject from within the recent kinase-thematic issue of Current Topics in Medicinal Chemistry.

With this as a backdrop, here’s another very interesting structure from SGC: 2VAG is Clk1 bound to a dichloroindole. If it is indeed as potent as has been suggested to me, then I might be moving towards believer status.


The animation shows their earlier 1z57 with Hymenialdisine, a somewhat more traditional kinase inhibitor.

Posted in General Interest | 20 Comments »