Beyond the MEK-pocket: can current MEK kinase inhibitors be utilized to synthesize novel type III NCKIs? Does the MEK-pocket exist in kinases other than MEK?
An approach and preliminary results for utilizing legacy MEK inhibitors as templates for a reiterative structural based design and synthesis of novel, type III NCKIs (non-classical kinase inhibitors) is described. Evidence is provided that the MEK-pocket or pockets closely related to it may exist in kinases other than MEK.
Tecle
Haile
H
Pfizer Global Research and Development, Research Technology Center, Cambridge, MA 02139, USA. haile.tecle@pfizer.com
Shao
Jianxing
J
Li
Yanhong
Y
Kothe
Michael
M
Kazmirski
Steven
S
Penzotti
Julie
J
Ding
Yuan-Hua
YH
Ohren
Jeffrey
J
Moshinsky
Deb
D
Coli
Rocco
R
Jhawar
Nidhi
N
Bora
Emilia
E
Jacques-O'Hagan
Suzanne
S
Wu
Joe
J
D020134:Catalytic Domain; D015195:Drug Design; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D047428:Protein Kinase Inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases