Non-peptidic small molecule inhibitors of XIAP.
Non-peptidic small molecule SMAC mimetics were designed and synthesized that bind to the BIR3 domain of XIAP using structure-based design. Substituted five-membered heterocycles such as thiazoles and imidazoles were identified that serve as replacements for peptide fragments of the lead.
Park
Cheol-Min
CM
Cancer Research, Global Pharmaceutical R and D, Abbott Laboratories, 100 Abbott Park Rd, Abbott Park, IL 60064-6010, USA. cheol-min.park@abbott.com
Sun
Chaohong
C
Olejniczak
Edward T
ET
Wilson
Alan E
AE
Meadows
Robert P
RP
Betz
Stephen F
SF
Elmore
Steven W
SW
Fesik
Stephen W
SW
D001665:Binding Sites; D015195:Drug Design; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D011506:Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology; D051636:X-Linked Inhibitor of Apoptosis Protein
D006571:Heterocyclic Compounds; D007093:Imidazoles; D008024:Ligands; D011506:Proteins; D013844:Thiazoles; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human