PDB Update

Merck (WP) Chk1, 2R0U: BMCL

Boo!

Tasigna Approved

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

wiki; clinic; WO/2002/022597

WO/2007/084560

Celgene S.D. aka Signal has a series of v600e active thienopyrimidines that also appear to hit the non-kinase PDE4.

WO/2007/084560

(NH2 > S)

MT-477

Buy this compound?

From: WO/2006/010127 and recently described as inhibiting PKC.

Go ahead, laugh it up – but hey, it could always be worse:

Selective vs. Nonselective

There are a handful of ways to visualize selectivity among kinase inhibitors after you’ve had them Profiled.

The gold standard has become the Ambit panel:

 

(from the Nature Biotech paper)

A simple chart will get the job done:

(INNO-406 / NS-187, from Blood 05, 3948)

or a heat map like Amphoras’:

If you prefer a reductionist approach you’ve always been able to take it down to a single number with fold shift from its nearest neighbor.

And now it looks like there may be a statistically more meaningful number with the recent J Med Chem on applying the Gini Coefficient to kinase inhibitor selectivty. In case you missed it, check out the spreadsheet in the supporting info.

PDB Update

2O5K, GSK3, 3.2A, CrystalGenomics: BMCL (re-refine phenol plz)

2REI, Epha7, 1.6A, SGC

2QVS, PKA, 2.5A, UCSD: Science:

AACR NCI EORTC

Abstracts are up, and B is the one you’ll be looking for.

News of the day:

In pts [patients] with PRC, XL-880 demonstrated antitumor activity

Name	Target	Company	Phase
AZD-2171	Vegf c-Kit Pdgfr-β	AstraZeneca	ph2
AZD-2171	Vegf c-Kit Pdgfr-β	AstraZeneca	ph2
PD-325901	Mek	Pfizer	ph2
XL-647	ErbB1,2 Vegfr-2	Exelixis	ph2
XL-880	c-Met Vegf	Exelixis	ph2
ARQ-197	c-Met	Arqule	ph1
BAY-579352	Vegfr-2,3 c-Kit Pdgfr-β	Bayer	ph1
BAY-734506	c-Kit Ret Pdgfr Raf	Bayer	ph1
BIBW-2992	ErbB (irrev)	BI	ph1
PD-325901	Mek	Pfizer	ph1
PF-299804	ErbB (irrev)	Pfizer	ph1
Ticribine	Akt	VioQuest	ph1
XL-647	ErbB 1,2 Vegfr-2	Exelixis	ph1
XL-820	Vegfr c-Kit Pdgfr	Exelixis	ph1
XL-880	c-Met Vegf	Exelixis	ph1
ARRY-543	ErbB1, 2	Array	ph1
AT-13148	Akt Rock PKA	Astex
AV-951	Vegf	Aveo	ph1
BAY-734506	c-Kit Ret Pdgfr Raf	Bayer
BMS-698769	c-Met	BMS
CEP-11981	Tie2 Vegfr	Cephalon
CUDC-101	HDAC / ErbB	Curis
NVP-BEZ235	Pi3k	Novartis
OSI-906	IGF-1R	Osi
RDEA-119	Mek	Ardea
SGX-523	c-Met	SGX
SR-13654	Src	SRI
XL-765	Pi3k, mTOR	Exelixis
XL-820	c-Kit	Exelixis
XL-844	Chk1, 2	Exelixis
ZD-6474	Vegfr-2 EGFR
ZM 447439	Aurora
CRT-59359	PKD	CRT

Duplicates and phase field just reflect the subject of the poster / reported trial, click for more details.

Weekend Reading

Imagine that, a Chem Rev I’m actually going to read?

Cl – – – – O

I am somewhere between faithless and agnostic on the role of through space ‘halogon bonding’, but earlier a reader pointed us towards a review on the subject from within the recent kinase-thematic issue of Current Topics in Medicinal Chemistry.

With this as a backdrop, here’s another very interesting structure from SGC: 2VAG is Clk1 bound to a dichloroindole. If it is indeed as potent as has been suggested to me, then I might be moving towards believer status.

The animation shows their earlier 1z57 with Hymenialdisine, a somewhat more traditional kinase inhibitor.