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Archive for the ‘SRC’ Category

PDB Update

Posted by kinasepro on October 29, 2008

Aurora A + 680: 3E5A; Protien Sci

Aurora B: 2VGO; Mol Cell Ther

SRC: 3EL7 & 3EL8; Chem Biol;

EPHB4: 2VWX; 2VWY; 2VX0, 2VX1

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Posted in Aurora, EphB4, PDB, SRC | 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 »

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)

N#CC1=CN=C2C=C(OCCCN3CCN(C)CC3)C(OC)=CC2=C1NC4=CC(OC)=C(Cl)C=C4Cl

Roche talks P38: R1487

CN1C2=NC(NC3CCOCC3)=NC=C2C=C(OC4=C(F)C=C(F)C=C4)C1=O

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

O=C(C(N1C)=CC2=C1C=CC=C2)NC3=CC=C(C4=NN([C@H]5CC[C@H](N6CCN(C(C)=O)CC6)CC5)C7=NC=NC(N)=C74)C=C3OC

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 »

2 PDBs today

Posted by kinasepro on November 21, 2006

Today’s update to the PDB contains two interesting SRC / Abl inhibitors.

BMS’s dasatinib in Abl is 2GQG

Astra’s AZD0530 in SRC is 2H8H

Posted in Astra, bcr abl, BMS, PDB, SRC | Leave a Comment »

US20060247250

Posted by kinasepro on November 4, 2006

Hi TargeGen, I see you’ve got another handful of compounds in another SRC inhibitor application. I guess selectivity has never been a real big thing down there in San Diego. These look suspiciously like dasatinib and are just the ‘reverse-amides’ from an earlier TG series (WO2006101977). I wonder what the ABL inhibition looks like for these…

Nice work finding a niche that doesn’t seem to have been covered anyhow.

O=C(NC1=C(C=CC=C1Cl)Cl)C(C=N2)=CN=C2NC3=CC=C(S(=O)(NCCN4CCCC4)=O)C=C3

Posted in biotech, SRC | Leave a Comment »

US20060247217

Posted by kinasepro on November 4, 2006

Not terribly new, but none-the-less entertaining. This is a divisional application of Wyeth’s 6,6,6 5,6,6 and 6,5,6 tricycles. They are SRC inhibitors, and there’s already a J. Med. Chem.

N#CC1=C(NC2=C(Cl)C=C(Cl)C(OC)=C2)C3=CC4=CC(OC)=C(OCCCN5CCOCC5)C=C4C=C3N=C1

Posted in SRC, Wyeth | Leave a Comment »

TG100801

Posted by kinasepro on November 1, 2006

Hi TargeGen. So whats with the new VEGF compound, eh?  Oh well. I also see you’ve disclosed that it’s an ester prodrug that hits VEGFR2 / PDGFR / SRC so its either a pyrimidine from WO2006101977 or a benzotriazine from the BMCL / ( US20050245524):

Using reverse logic, they’d probably publish the series that didn’t work right? Ergo, I’d put my bet down on the pyrimidines. The chloro-phenol of the above prodrug is 1.8 nM on SRC and single digit on EphB4 / PDGF / YES. I’d say these are a go for efficacy, but Tox?

>> Update 11/02 US20060247250 is a patent application which houses SRC/VEGF compounds, claims eyedrop formulations… and they’re pyrimidines.

Posted in biotech, SRC, VEGF | 1 Comment »

US7125875

Posted by kinasepro on October 26, 2006

The claims are basically: Swallow Dasatinib wherein the cancer is Gleevec resistant. Read the J Med Chems (here, and here). BMS has been prolific in writing about their aminothiazoles and there’s plenty of bioorg med chem lett’s too. For anyone who’s been living under a rock for the last couple years, Dasatinib is BMS’s SRC / ABL compound. They use the (cough*stupid*cough) term ‘pan-SRC selective’ since it hits: YES / LCK / LYN / FYN / etc.

…and thats just the profile they want to tell us about…

PDB = 2GQG

O=C(C2=CN=C(NC3=NC(C)=NC(N4CCN(CCO)CC4)=C3)S2)NC1=C(C)C=CC=C1Cl BMS35482513 Dasatinib

Posted in bcr abl, BMS, Granted, SRC | Leave a Comment »

Couple-a-new-PDB’s

Posted by kinasepro on October 24, 2006

2BDF, and 2BDJ

These are the SRC / Abl phosphine oxide bearing purines from Ariad. Good stuff with a free bonus link to the published discussion: Chem Biol Drug Des 2006, 46.

OC1=CC=CC(CCN2C=NC3=C2N=C(C4CCCC4)N=C3NC5=CC=C(P(OC)(OC)=O)C=C5)=C1x-ray crystallography, SRC/ABL AP23464 AP23451 CCN2C=NC1=C(NC3=CC=C(P(O)(CP(O)(O)=O)=O)C=C3)N=C(C4CCC(N)CC4)N=C12 CP(C(C=C5)=CC=C5NC1=C(N=CN2CCC3=CC(O)=CC=C3)C2=NC(C4CCCC4)=N1)(C)=O

Posted in biotech, PDB, SRC | Leave a Comment »