The commonly used PI3-kinase probe LY294002 is an inhibitor of BET bromodomains

Antje Dittmann, Thilo Werner, Chun-Wa Chung, Mikhail M Savitski, Maria Fälth Savitski, Paola Grandi, Carsten Hopf, Matthew Lindon, Gitte Neubauer, Rabinder K Prinjha, Marcus Bantscheff, Gerard Drewes
ACS Chemical Biology 2014 February 21, 9 (2): 495-502
A commonly used small-molecule probe in cell-signaling research is the phosphoinositide 3-kinase inhibitor LY294002. Quantitative chemoproteomic profiling shows that LY294002 and LY303511, a close analogue devoid of PI3K activity, inhibit the BET bromodomain proteins BRD2, BRD3, and BRD4 that comprise a family of targets structurally unrelated to PI3K. Both compounds competitively inhibit acetyl-lysine binding of the first but not the second bromodomain of BET proteins in cell extracts. X-ray crystallography shows that the chromen-4-one scaffold represents a new bromodomain pharmacophore and establishes LY294002 as a dual kinase and BET-bromodomain inhibitor, whereas LY303511 exhibits anti-inflammatory and antiproliferative effects similar to the recently discovered BET inhibitors.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"