Non-thiol farnesyltransferase inhibitors: utilization of the near aryl binding site by 5-arylacetylaminobenzophenones.
We recently described two novel aryl binding sites of farnesyltransferase. The arylacetyl residue was designed as an appropriate substituent for our benzo-phenone-based AAX-peptidomimetic compound capable of occupying the near aryl binding site which is located next to the catalytic zinc ion. Non-thiol farnesyl-transferase inhibitors with micromolar to submicromolar activity were obtained.
Mitsch
Andreas
A
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, D-35032 Marburg, Germany.
Böhm
Markus
M
Sattler
Isabel
I
Schlitzer
Martin
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D001577:Benzophenones / Q000138:chemical synthesis / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D001577:Benzophenones; D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase