Journal article
Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis
M Nguyen, RC Marcellus, A Roulston, M Watson, L Serfass, SR Murthy Madiraju, D Goulet, J Viallet, L Bélec, X Billot, S Acoca, E Purisima, A Wiegmans, L Cluse, RW Johnstone, P Beauparlant, GC Shore
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2007
Abstract
Elevated expression of members of the BCL-2 pro-survival family of proteins can confer resistance to apoptosis in cancer cells. Small molecule obatoclax (GX15-070), which is predicted to occupy a hydrophobic pocket within the BH3 binding groove of BCL-2, antagonizes these members and induces apoptosis, dependent on BAX and BAK. Reconstitution in yeast confirmed that obatoclax acts on the pathway and overcomes BCL-2-, BCL-XL-, BCL-w-, and MCL-1-mediated resistance to BAX or BAK. The compound potently interfered with the direct interaction between MCL-1 and BAK in intact mitochondrial outer membrane and inhibited the association between MCL-1 and BAK in intact cells. MCL-1 has been shown to co..
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