BI-6727

BI’s PhII follow on to BI-2536

PDB: 3FC2; Clin Can Res

Takeda’s got PLK1

WO/2009/042806 & WO/2009/042711

process app.

BI-2536

BI’s Ph2 PLK1 inhibitor

IV / 0.8 nM

ON-01910

Onconova’s IV Ph2 PLK1′inhibitor’

“…a new chemical entity that arrests cancer cells in G₂/M by modulating mitotic regulatory pathways including polo-like kinase 1 (Plk1).” via WO/2008/088803

PDB Update

Buncha-new Plk1 PDB’s

Plk1: 3DBF, 3DBE, 3DBD, 3DBC, 3DB8

new c-Met: 3EFK, 3EFJ

new Vegf: 3CJG, 3CJF

R & D @ B I

With BIRB-796 a distant memory, BIBW-2992 in ph3 and given the new name Tovok, BIBF-1120 headed into ph3 and given the name Vargatef,  BI-2536 in multiple Ph2s, a new Ph1 Aurora inhibitor, and another backup PLK1 inhibitor undisclosed, but likely in-clinic or clinic-bound – what could possibly be next?

I can haz pyrimidines

PDK mod prolly from Berlex

Some highlights…

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.

BI’s PLK1 compound

WO/2007/90844 is a salt form application of a compound that we’ve seen before ’round here.

discovery: WO/2003/020722, WO/2004/076454

PDB Update

>> Update >> Biochemistry article on the Plk1 structure.

Woohoo! First published kinase domain Plk1 structures from Pfizer:

2OWB Plk1 w/ pyrrolopyrazole inhibitor
2OU7 Plk1 w/ ANP

and a Chk1 structure from Merck: 2HOG; BMCL

DE102005020104

and DE102005020105. Guten Tag Schering AG,

Further along the road with the thiazolidinones, eh?  I like the title: New thiazolidinone without basic nitrogen, their production and use as drugs

Kinasepro is always happy to see more Plk1 inhibitors, but hey I’ll admit that I haven’t a clue whats going on with these – and now consider an earlier post on your analogous series, ummm, wrong. The only PDBs that give KP a hint as to what could be going on here are from some compounds bound to PI3K: 2A4Z, and 2A5U. O=C(N(CC)/C(S2)=C(C(NCC(F)(F)F)=O)\C#N)/C2=C/C1=C(C)N=CN1 O=C(N(CC)/C(S2)=C(C(NCC#C)=O)\C#N)/C2=C/C1=CC=C(N3CCCC3)C=C1