Wyeth gets Jak’d up!

via Jak3 but of course – in an underanounced deal with Pharmacopeia:

…Wyeth will pay Pharmacopeia $5 million initially, as much as $9 million of research funding over the next three years, and as much as $175 million for reaching certain goals with the JAK3 kinase inhibitor drug.

While it’s likely they have a few which haven’t published yet, WO/2006/108103 is the most recent PCOP Jak3 application.

They’ve been at this stuff for a while – I reckon since WO/2001/047921 and have a recent Tet Lett on a related series. Check 2HK5 for a clue on how they bind.

>> update 1/25/07 >> US20070021443 Jak3 Pharmacopeia patent application

Better Chemistry = Better Drugs

Wull Duh? But in this case it’s a webcast on medchem from some mostly non-chemists: David Snitman, Paul Goddard, Arthur Sands, and Jim Mahoney of Array, ARYx, Lexicon, and Surface Logix respectively.

US20060293358

Merck MA‘s got Met

The Thursday List

US20060293358 Met Merck
US20060293348 p38 GSK
US20060293340 Raf Novartis
US20060293342 Tie2 EXEL
US20060293311 Jak3 Rigel
US20060292681 Interdomain kinase inhibitors
WO/2006/137598 c-Jun Sumitomo
WO/2006/136837 AKT Astex
WO/2006/136402 Mnk Develogen

Tykerb + Xeloda 4TW

Good news for Tykerb and GSK.

Xeloda + Avastin ph ii was reported earlier this month.

PDB Update

2NP8: Aurora Kinase. Novartis has a series of these kinds of compounds described in: JACS ’06 – 2182, but its looking like this came out of Takeda, and the companion article to this xray is in the ‘to be published’ category. Only other Aurora relevant Xray is a mutant: 2C6E, and of course the Abl mutant with VX680: 2F4J.

Interesting, looks that there’s a lysine residue on the glycine rich loop which is fairly specific to Aurora and appears to hydrogen bond the trifluromethyl group. Else these look to be in a similar conformation to the Rigel pyrimidines.

Also new today: 2FGA; Chk1 Apo: Bioorg Med Chem Lett ’06 – 2293 Peculiar, this is a low resolution apo with identity to the much earlier high resolution Chk1 apo: 1IA8.

WO2006135604

WO2006135604 is a recent Chk1 offering via Merck.

ENMD-981693

Entremed has an ‘Aurora A selective’ preclinical candidate ENMD-981693, which is likely MKC-1693 or closely related. Here’s a poster given earlier this month. The structure has not been divulged, but the compound most likely came from the purchase of Miikana’s IP. There’s only one Miikana publication on Aurora and its the patent application: WO2006055831 which comprise a series of amides (and esters):

look familar?

So lets review:

	VX680 (nM)	ENMD-981693 (nM)
Aurora A	0.6	15
Aurora B	18	290
Aurora C	4

New Greene

1082 pages? Drats, didn’t make my Christmas list: 4th Edition. Don’t forget the 25% off for authors.

Just in time for Christmas

It usually takes KP a year and a half to find information because that’s when the applications publish… In this case the only excuse is that he’s a little slow. I’m talking about the BindingDB and it appears to be a (smiles substructure searchable) resource with a ton of potential that’s been around since 5/05 but didn’t find the other end of my mouse button till today.

Also Current Opinion in Structural Biology has stuffed our stocking a little early with a thematic issue on you guessed it: kinases. Ok so is not all kinases, but 5 reviews aint bad.