AT-9283

Astex’s unpartnered JAK/Aur/Abl Ph1b nib

poster; clinic; PDB: 2W1G & 2W1I

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.

Tasigna Approved

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

wiki; clinic; WO/2002/022597

PDB Update

Big week

2QOH; PPY-A bound to Abl via Ariad; Chem Biol Drug Des
2Z60; PPY-A bound to T315I Abl

(compounds from SGX)

2OH4; Benzimidazole bound to VEGF via GSK JP; J Med Chem

2V7A; PHA-739358 bound to T315I mutant of Abl via Nerviano; Cancer Res

2IN6 Wee1
2IO6 Wee1

LS-104

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

WO/2005/092904

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

TargaGen closes…

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.

wt Abl 1.5 nM
T315I 18 nM

So you like pictures?

Who’s in CA?

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)

Roche talks P38: R1487

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

all great compounds and yadda yadda, just having a hard time seeing anything new here.

AP24534 In here?

Everyone looking at Abl these days is trying to wiggle their way around T315 and Ariad’s latest go is described in the app: WO/2007/021937 with a series of styrene-purines. They look to be a follow-on series to the earlier purine stuff described elsewhere.

Structures for their two previous SRC/ABL leads: AP23464 and AP23451 were disclosed but afaik AP24534 has not.

INNO-406

Making some bold claims, Innovive gets orphan status for INNO-406 / NS-187

…speechless

BMS-354825 vs. VX-680

At least the PDB gave us something to look at a few days ago. Here’s a super-cool alignment of dasatinib in Abl to VX-680 in an abl mutant.