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AEG35156 is a 2nd generation antisense oligonucleotide which targets XIAP; it is designed to lower the apoptotic threshold of cancer cells, enhancing their sensitivity to intrinsic death and chemotherapy, without harming healthy cells. AEG35156 has completed its first Phase 2 trial in refractory AML patients and will shortly be enrolling in a randomized Phase 2 study in the same indication. Other enrolling studies include a Phase 1/2 monotherapy study in CLL/indolent B-cell lymphomas, which is fully funded by The Leukemia and Lymphoma Society, and a Phase 2 randomized combination study with sorafenib in first-line hepatocellular carcinoma being conducted in Hong Kong.
This schematic illustrates XIAP’s pivotal role as the most potent endogenous inhibitor of caspases 3, 7 and 9. XIAP inhibits apoptosis induced by cues which trigger the intrinsic mitochondria-mediated cell death pathway as well as the extrinsic death receptor-mediated cell death pathway via the inhibition of these key initiator and effector caspase enzymes.
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