ArticleFEBS open bio2021
The non-peptidomimetic IAP antagonist ASTX660 sensitizes colorectal cancer cells for extrinsic apoptosis.
Article in FEBS open bio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- IAPs in cancers: molecular mechanisms, clinical prognostic value, and translational therapeutic potential.Journal of translational medicine · 2026Review
- The lncrnas: innovative multifunctional players of drug resistance in colorectal cancer.Cancer cell international · 2025Review
- Apoptosis evasion via long non-coding RNAs in colorectal cancer.Cancer cell international · 2022Review
- Tumor-intrinsic and immune modulatory roles of receptor-interacting protein kinases.Trends in biochemical sciences · 2022Review
- Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis resistance worsens treatment response in cancer and is associated with poor prognosis. Inhibition of anti-apoptotic proteins can restore cell death and improve treatment efficacy. cIAP1, cIAP2, and XIAP belong to the inhibitor of apoptosis protein (IAP) family and block apoptosis. Targeting IAPs with peptides or peptidomimetics mimicking the IAP-antagonizing activity of the cell's endogenous IAP antagonist SMAC (SMAC mimetics) showed promising results and fueled development of novel compounds. ASTX660 belongs to the recently introduced class of non-peptidomimetic IAP antagonists and successfully completed phase I clinical trials. However, ASTX660 has thus far only been evaluated in few cancer entities. Here, we demonstrate that ASTX660 has cell death-promoting activity in colorectal cancer and provide a head-to-head comparison with birinapant, the clinically most advanced peptidomimetic IAP antagonist. ASTX660 facilitates activation of the extrinsic apoptosis pathway upon stimulation with the death ligands TNF and TRAIL and boosts effector caspase activation and subsequent apoptosis. Mechanistically, ASTX660 enhances amplification of death receptor-generated apoptotic signals in a mitochondria-dependent manner. Failure to activate the mitochondria-associated (intrinsic) apoptosis pathway attenuated the apoptosis-promoting effect of ASTX660. Further clinical studies are warranted to highlight the therapeutic potential of ASTX660 in colorectal cancer.
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Registered trials
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