PDB Update

2pzy: MK2; BI; BMCL:

That p-loop interaction sure is interesting

and the s-o is 2.87Å.

2DWB: Aurora A; ANP; RSGI

S – – – – O

I thought this was pretty well known, but looking at some recent literature along with Ashutosh, I guess its worth highlighting. The short of it is that if you need it in plane maybe you aughta see what it looks like with a sulfur atom.

Dasatinib is one such example where the carbonyl is in plane with a heteroaromatic Sulfur atom, but there are plenty of more where that came from…

clinical roundup

Supergen initiates dosing of flt3 inhibitor MP-470: ph1 ‘advanced-stage solid tumors.’

Entremed initiates trial for Aurora inihbitor MKC-1: Ph1 Leukemia

Kinex gets the FDA go-ahead for Src inhibitor KX2-391: lymphoma or solid tumors (though despite the press release, it’s not the first non-atp competitive kinase inhibitor to enter the clinic. The MEK inhibitors were)

The Thursday List

WO/2007/082470 Shanghai Henriu
WO/2007/082956 pi3k Serono
WO/2007/083017 IGFl-R Aventis
WO/2007/083096 aurora AstraZeneca
WO/2007/083978 GSK3, Aurora Crystal Genomics
WO/2007/084391 PKB Amgen
WO/2007/084557 Jak Vertex
WO/2007/084560 bRaf Signal
WO/2007/084667 Rho OSI
WO/2007/084728
WO/2007/084786 pi3k Novartis (Chiron)
WO/2007/084815 EGF JnJ
WO/2007/084857 Resveratrol Harvard
WO/2007/084875 EGF&Vegf

US20070173649 p38 Vertex
US20070173537 vegf Mitsubishi
US20070173530 Aerie
US20070173525 IGFR? Merck
US20070173519 MK2 Teijin
US20070173516 Aurora Vertex
US20070173506 PKB Amgen
US20070173503 CDK2 Sanofi-Aventis
US20070173500 Allergan
US20070173488 cMet etc. SGX

PDB Update

2PZI: AX-20017 in PknG, Biozentrum (University of Basel) & PSI; PNAS

IC50 of ~0,5μM

AX-20017 was a hit, and optimized in: WO/2005/023818 by Axxima now owned by GPC. Some off-target activity on Aurora is described in the series, and here’s some related Flt3 inhibitors: BMCL

Oximes from J&J

So J&J has a BMCL describing the amino-pyrimidine-oxime moiety as quinazoline isostere, and a there’s a handful of other applications describing the motif.   Here’s a Lapatinib-esque example where they describe the EGF activity: WO/2007/081630

< 2g/d plz

Schering’s Macrocycles

Aurora Eh? What can I say, I like’m: WO/2007/079982

Related series, complete w/ a Chem Med Chem.

The Thursday List

WO/2007/082296 Xtals-EphB4 Scripps
WO/2007/082079 p38 Scripps
WO/2007/081978 c-Met Angion
WO/2007/081901 p38 Scripps
WO/2007/081690 “open conformation” p38 Locus
WO/2007/081630 Egf JnJ
WO/2007/081572 Chk1 Merck
WO/2007/081560 Vegf+ Scripps
WO/2007/081060
WO/2007/080392 Vegf / EGF Domantis
WO/2007/080382 mTor / Pi3k AstraZeneca
WO/2007/080325 FGF agonist Sanofi-Aventis
WO/2007/080324 p38 Sanofi-Aventis
WO/2007/079999 Zentaris
WO/2007/079982 Aurora Schering AG
WO/2007/079826 Merck DE
WO/2007/079820 Tgf-b Merck DE

US20070167439
US20070167621 p38 Pharmacia
US 20070167484 p38 Roche
US20070167471 p38 Roche
US20070167469 Sanofi-aventis
US20070167467 p38 GSK
US20070167466 CDK
US 20070167461 GSK3 Sanofi-aventis
US20070167449 Flt3 Novartis
US20070167443 Tie2? Chemocentryx
US20070167439 Syk Rigel
US20070167413 p38 Orchid
US20070167410 Vegf+ Novartis (GNF)

Correction

Pfizer’s Jak3 inhibitor CP-690,550 was described earlier listed as Ph ii-iii. For some reason that was changed, and all of its furthest advanced trials are Phase 2.

/. does CDK5

For my read, the story is less that MIT CURES PHEAR! and more that, heh – slashdot picked up a kinase related press release – then proceeded to mangle it. 😦 Nobody tell Derek.

In our study, we employ mice to show that extinction of learned fear depends on counteracting components of a molecular pathway involving the protein kinase Cdk5

MIT Press release; Nature Neuroscience; Falculty page