KinasePro

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

Archive for the ‘biotech’ Category

TTP-607

Posted by kinasepro on September 2, 2007

TTP-607 is described as the lead in a series of Aurora Kinase inhibitors from TransTech. It seems likely to be derived from WO/2007/95124:

O=C(C3=C(N6CCNCC6)C=C(N=C(NC5=C(C(F)(F)F)C=CC=C5)N4)C4=C3)NC1=CC2=C(C=NN2)C=C1

Posted in Aurora, biotech | 14 Comments »

AZ’s GSK3 Indolinone

Posted by kinasepro on August 10, 2007

WO/2007/089192 is a use app, and WO/2007/089191 is salt forms application of the pictured GSK3 inhibitor originally from WO/2003/08285.  The YM-231146 / YM-359445 series bears similarity, albeit for Vegf.

N#CC1=CC2=C(NC(/C2=C3C=CC(CN4CCOCC4)=CN\3)=O)C=C1

The PDB used for alignment is 1UV5, and you can also check out AZ’s publicized interest in selective GSK3 inhibition in an ’03 JBC and 1q5k.

Posted in Astra, biotech, GSK3 | 2 Comments »

LS-104

Posted by kinasepro on August 9, 2007

The news today is that LS-104 is in Ph1 and now owned by Aegera from Lymphosign who in turn licsensed it from HSC. Their portfolio of patent applications suggests the compound is likely a tyrphostin derivative.

LS104 is a novel small molecule tyrosine kinase inhibitor of therapeutically significant kinases including Jak2 and Bcr-Abl…In contrast to marketed kinase inhibitor drugs, LS104 inhibits its targets in a non-ATP-competitive manner

N#C/C(C(NCC1=CC=C(O)C(O)=C1)=O)=C\C=C\C2=CC(OC)=C(O)C(OC)=C2

WO/2005/092904

I don’ t know about you but I needed a history lesson to get a handle on these

Posted in bcr abl, biotech, JAK | 2 Comments »

TargaGen closes…

Posted by kinasepro on July 13, 2007

Closes a 40M series D that is. Kudos Pros. Some of the more recent thiazole apps like US20070161645 appear to my eye to be the Src/Abl backup brigade.

CC1=NC(NC2=NC=C(/C=C/C3=CC(O)=CC=C3)S2)=CC(N4CCNCC4)=N1

wt Abl 1.5 nM
T315I 18 nM

So you like pictures?

Read the rest of this entry »

Posted in bcr abl, biotech, SRC | 2 Comments »

KX2-391

Posted by kinasepro on June 21, 2007

Kinex filed an IND today for this ‘ere compound:

O=C(CC1=NC=C(C=C1)C2=CC=C(C=C2)OCCN3CCOCC3)NCC4=CC=CC=C4

KX-01, KX2-391, ALB-30350, wait, ALB-30350? yah…

from WO/2006/071960:

Note that KX2-391 has weak activity against isolated kinases because the peptide binding site is not well formed outside of cells (a close analog, KX2-394 is a little more potent against isolated Src [KP note: 394 is the piperazine]), but have very potent activity inside whole cells. Without wishing to be bound by theory, it is thought that the difference in activity is attributed to the fact that the peptide binding site is now fully formed in cells due to the allosteric effects of the binding protein partners in the multi-protein signaling complexes, relative to isolated kinase assays.

Posted in biotech, SRC | 10 Comments »

ENMD-981693

Posted by kinasepro on June 1, 2007

So Entremed is over in Boston stumping for their Aurora inhibitor and they happened to drop the MW and cLogP:

CC1=CC(NC2=NC(/C=C/C3=CC=CC=C3)=NC(N4CCN(CC4)C)=C2)=NN1

Only two compounds from WO/2007/041358 fit that bill. That one, and the Z isomer.

Posted in Aurora, biotech, Flt3, multi-target | 4 Comments »

4SC: Aurora B

Posted by kinasepro on May 23, 2007

COC1=CC2=C(C=C1OCCCN3CCCC3)N=CN=C2NC4=NC=C(CCC(NC5=CC=C(F)C=C5)=O)S4

WO/2007/054357 is another example showing an isosteric relationship between pyrazoles and thiazoles.

Posted in Aurora, biotech | Leave a Comment »

MP-470

Posted by kinasepro on May 17, 2007

S=C(N3CCN(C4=NC=NC6=C4OC5=CC=CC=C56)CC3)NCC2=CC1=C(C=C2)OCO1

Supergen just gave an update in Italy yesterday: webcast here. Skip to ~7 minutes for the kinase portion. The highlight for me is on MP-470 where he says that its uM on met (and ret).

but at AACR last year they suggested that:

In their defence I’ll postulate that they meant 4,000 nM concentrations last year. Ultimately does it matter? Only in so far as how much you can trust what they say… heh

Posted in biotech | 16 Comments »

VQD-002

Posted by kinasepro on May 2, 2007

Vioquest recently gave an update on their ph i/iia study with this here nucleotide. Nearly as old as ATP itself, the compound was made new again by a diagnostic screen for cancers overexpressing AKT.

NC1=NN(C)C2=C3C(N([C@H]4[C@@H]([C@@H]([C@@H](COP(O)(O)=O)O4)O)O)C=C13)=NC=N2

Also goes by: API-2, NSC-154020, TCN-P, and triciribine phosphate. and yeh, somebody got the structure wrong in Cancer Res. 04, 4394

(KSR v. Teleflex? suck it.)

Posted in AKT, biotech | Leave a Comment »

PX-866

Posted by kinasepro on April 17, 2007

PX-866 is a Wortmannin analog that came to Biomira as part of the Prolx deal.

O=C1/C(C([C@]2(C)[C@@H](COC)O1)=C(O)C(C3=C2[C@H](OC(C)=O)C[C@@]4(C)[C@@]3([H])CCC4=O)=O)=C/N(CC=C)CC=C

You synthetic junkies should recognize at least one of the names on the patent app. Appears to be a simple improvement to the michael acceptor.

1E7U shows the natural product covalently bound to Pi3k

O=C1C2=COC3=C2[C@](C([C@H](OC(C)=O)C[C@]45C)=C([C@@]5([H])CCC4=O)C3=O)(C)[C@@H](COC)O1

Posted in biotech, pi3k | Leave a Comment »

 
Follow

Get every new post delivered to your Inbox.