KinasePro

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

Archive for November, 2007

Death by SGC

Posted by kinasepro on November 30, 2007

SGC’s got another pre-release, this one’s a ligated DAPK3A; soon to be: 3BHY

striking an impressive pose @ 1.24Å

CN2C3=C([C@@H](C#N)C4(CCN(C)CC4)NC3=O)C1=CC=C(Cl)C(Cl)=C12

died and gone to pdb heaven

Posted in PDB, SGC | 2 Comments »

SGC: PDB Update

Posted by kinasepro on November 29, 2007

Get y’r red-hot CAMK2B pre-release right here. 3BHH is a tetramer, with both an apo and a ligated forms represented.

Posted in Camk, PDB, SGC | 1 Comment »

Some highlights…

Posted by kinasepro on November 28, 2007

GSK’s been looking at Plk1 for quite a while. Sure the structure was in an earlier application (March), but here it is better late then never. See: WO/2004/074244, WO/2004/087652, WO/2005/019193, WO/2007/030361, US20070010668, & US20070270437

AP-24534 In here? Earlier Ariad had a double bond wiggling around T315I, in WO/2007/133560 & WO/2007/133562 it’s a triple bond.

And Vertex has an interesting series of series of Rock inhibitors in WO/2007/133622. Ki is reported to be <100 nM and clean across the cyps.

Oh yah, and if your curious about Cyclacel’s Aurora inhibitor CYC-116, they’ve narrowed it down to 1 of 3 for you and they also give an in vitro panel in WO/2007/132220, WO/2007/132221, WO/2007/132228. The claims make it look like the morpholine.

Posted in Ariad, bcr abl, Cyclacel, GSK, Plk1, Rho, Vertex | 4 Comments »

Astex: An Oral Candidate for CDK2

Posted by kinasepro on November 23, 2007

Astex’s fragment based discovery effort yielded an oral candidate back in ’05, and now with WO/2007/129066 & WO/2007/129062 the world can have a look. It’s probably AT-9311 even though I could’a swore I heard’m say that their Novartis’ partnered material was of a different series then AT-7519. Perhaps its 7519 I have wrong…

O=C(C2=NNC=C2NC(C3=C(Cl)C=CC=C3Cl)=O)NC1CCN(S(=O)(C)=O)CC1.O=C(C5=NNC=C5NC(C6=C(Cl)C=CC=C6Cl)=O)NC4CCNCC4.N7=CC=CN7

pM CDK2
0.22 uM GSK3b
Mouse: 40-50%F (DMSO/Water/PEG 1/2/7)

Posted in Astex, CDK, CDK2 | 12 Comments »

VX-680, VX-667: Done

Posted by kinasepro on November 21, 2007

VX-680 halted as:

one patient experienced QTc prolongation.

O=C(C3CC3)NC(C=C4)=CC=C4SC1=NC(N2CCN(C)CC2)=CC(NC5=NNC(C)=C5)=N1

and the follow-on, VX-667:

Failed to meet pharmacokinetic objectives in a Phase 1 trial

Posted in Aurora, Merck & Co., Vertex | 15 Comments »

ARRY-797 goes to the dentist…

Posted by kinasepro on November 20, 2007

Promoted to ph2:

to evaluate the efficacy of ARRY-797 in the management of postoperative dental pain…

CC(F)(CN1C2=C(C=N1)C=C(C(C(N[C@](CCNC)(C(N)=O)CCC3CC3)=O)=C2)OC4=C(C=C(C=C4)F)F)C

still no structure disclosed afaik, but likely a cousin of the above.

Posted in Array, p38 | 5 Comments »

Pfizer’s Jnk

Posted by kinasepro on November 15, 2007

SD’s got a series of Jnk1 inhibitors in WO/2007/125405:

COC1=CC=C(CC(NC2=NC=C(C=CC(C4=CN(C)N=C4)=C3)C3=C2)=O)C=C1

First half of the compounds look about like that one, and Jnk1 data is given…
Second half appear discretely in the claims and look more like Jnk3 inhibitors to me.

Posted in biotech, Jnk, Pfizer | 3 Comments »

News of the day

Posted by kinasepro on November 14, 2007

 O=C(N([H])C2=CC=C(C3=CN4C(SC5=CC(N6CCN(C)CC6)=CC=C45)=N3)C=C2)N([H])C1=NOC(C(C)(C)C)=C1

aetiology and limited data in: WO/2005/048953

Posted in Ambit, Aurora, Deals, Flt3, Rigel | 16 Comments »

Banyu’s …

Posted by kinasepro on November 12, 2007

… got more Aurora A compounds in WO/07/126126:

InChI=1/C25H27ClFN7O2/c1-14-7-22(31-30-14)29-21-9-15(24(35)32(2)3)8-16(28-21)11-33-12-18-10-17(33)13-34(18)25(36)19-5-4-6-20(26)23(19)27/h4-9,17-18H,10-13H2,1-3H3,(H2,28,29,30,31)/t17-,18-/m0/s1

drawn with Depthfirst‘s Inchimatic.

Posted in Aurora, Banyu | 1 Comment »

R-788 (Fostamatinib disodium)

Posted by kinasepro on November 9, 2007

R-788 is Rigel’s SYK / Flt3 inhibiting prodrug of R-406, and despite a positive sounding press release on their Ph2 ITP study, the market is reacting negatively so far by knocking 20% off of the stock price.

r-788
the name suggests disodium.

Posted in Flt3, Rigel, SYK | 15 Comments »