The identification and optimization of 2,4-diketobutyric acids as flap endonuclease 1 inhibitors.
There have been several recent reports of chemopotentiation via inhibition of DNA repair processes. Flap endonuclease 1 (FEN1) is a key enzyme involved in base excision repair (BER), a primary pathway utilized by mammalian cells to repair DNA damage. In this report, we describe the identification and SAR of a series of 2,4-diketobutyric acid FEN1 inhibitors.
Tumey
L Nathan
LN
Athersys, Inc., 3201 Carnegie Ave., Cleveland, OH 44115, USA. ntumey@athersys.com
Huck
Bayard
B
Gleason
Elizabeth
E
Wang
Jianmin
J
Silver
Daniel
D
Brunden
Kurt
K
Boozer
Sherry
S
Rundlett
Stephen
S
Sherf
Bruce
B
Murphy
Steven
S
Bailey
Andrew
A
Dent
Tom
T
Leventhal
Christina
C
Harrington
John
J
Bennani
Youssef L
YL
D002087:Butyrates / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D045585:Flap Endonucleases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D002087:Butyrates; D004791:Enzyme Inhibitors; D045585:Flap Endonucleases