ArticleInvestigational new drugs2011
Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis.
Article in Investigational new drugs, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions.Antioxidants (Basel, Switzerland) · 2025Review
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- X-linked inhibitor of apoptosis protein represents a promising therapeutic target for relapsed/refractory ALL.EMBO molecular medicine · 2023Article
- Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment.Computational and structural biotechnology journal · 2019Review
- Sensitizing acute myeloid leukemia cells to induced differentiation by inhibiting the RIP1/RIP3 pathway.Leukemia · 2017Article
- Therapeutic targeting of necroptosis by Smac mimetic bypasses apoptosis resistance in acute myeloid leukemia cells.Oncogene · 2017Article
- Smac mimetic induces cell death in a large proportion of primary acute myeloid leukemia samples, which correlates with defined molecular markers.Oncotarget · 2016Article
- Article
- Inhibitor of Apoptosis (IAP) proteins in hematological malignancies: molecular mechanisms and therapeutic opportunities.Leukemia · 2014Review
- Genome-wide analysis of regulatory proteases sequences identified through bioinformatics data mining in Taenia solium.BMC genomics · 2014Article
- Dipyrithione induces cell-cycle arrest and apoptosis in four cancer cell lines in vitro and inhibits tumor growth in a mouse model.BMC pharmacology & toxicology · 2013Article
- Smac mimetic and demethylating agents synergistically trigger cell death in acute myeloid leukemia cells and overcome apoptosis resistance by inducing necroptosis.Cell death & disease · 2013Article
- Exploiting inhibitor of apoptosis proteins as therapeutic targets in hematological malignancies.Leukemia · 2012Review
- Targeting IAP proteins for therapeutic intervention in cancer.Nature reviews. Drug discovery · 2012Review
- Smac mimetic compounds potentiate interleukin-1beta-mediated cell death.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Inhibitor of Apoptosis Proteins (IAPs) are important regulators of programmed cell death. XIAP is the most potent among them and is over-expressed in several hematological malignancies. Its activity is endogenously antagonized by SMAC/DIABLO, and also by small molecules mimicking Smac that can induce apoptosis in tumor cells. Here we describe the activity of 56 newly synthesized Smac-mimetics in human leukemic cell lines and normal CD34(+) progenitor cells. Our compounds bind to XIAP with high affinity, reduce the levels of cIAP1 and are cytotoxic at nanomolar or low micromolar concentrations. Furthermore, the Smac-mimetics synergize with Cytarabine, Etoposide and especially with TRAIL in combination treatments. Apoptosis activation was clearly detectable by the occurrence of sub G(1) apoptotic peak and the accumulation of cleaved PARP, caspase 8 and caspase 3. Interestingly, the down-regulation of XIAP sensitized Jurkat cells to drugs too, confirming the role of this protein in drug-resistance. In conclusion, while being very active in leukemic cells, our Smac-mimetics have modest effects on normal hematopoietic progenitors, suggesting their promising therapeutic potential as a new class of anticancer drugs in onco-hematology, particularly when combined with TRAIL, to overcome the resistance of cancer cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.