Kinase Chemistry – Just a year and a half behind the times.

Archive for October 31st, 2006


Posted by kinasepro on October 31, 2006

Hi Again SKB, Nice AKT inhibitors.

This benzimidazole core keeps popping up in the patent literature… Maybe there’s something to it. I see you guys vary the heck out of the alkoxy-amino region. Some nice intermediates worth perusing there.

As for the binding motif, well, AKT appears to be difficult to crystallize, or else why would folks be looking at PKA mutants as PKB models? (1XH4, 1XH5, 1XH6, 1XH7, 1XH8, 1XH9, and 1XHA) KP is not aware of any PDBs with the core, and the two APO’s of akt are teh suq, but my feeling is that 2F7Z has some clues.

Yah, Yah I know the overlay is ‘backwards’ compared to the 2D models… Use your rimagination. This seems reasonable though and puts the oxadiazole at the hinge, the alkyne pointed towards H1, and the primary amine in the phosphate binding region. NC1=NON=C1C2=NC3=C(C#CC(C)(O)C)N=C(O[C@H]([C@H](COC)N)C4=CC=CC=C4)C=C3N2CC


Posted in AKT, GSK | 1 Comment »


Posted by kinasepro on October 31, 2006

Couple things…

  • Looks like Org Syn volume 84 is starting to roll out on the web.
  • Pipeline looks to be down today 😦
  • Some Canadian company, bought some company in Tucson that has some kinase inhibitors (Pi3K, and AKT) ‘in late preclinical development’. For those of us following along at home, that’s code for having compounds with A) crummy PK B) poor selectivity C) CYP issues – or more likely – all of the above. Only reason I can see to list all the programs in the press release is that they are now for sale. Any bets on what they do with the American side of the company?
  • Array announced its p38 program is ready for prime-time. (Of note Array has some of their patents applications downloadable) From that list it looks like plenty of MEK and AKT inhibitors… but P38? Yah there’s a couple from ’04.

Posted in biotech, General Interest | 3 Comments »