ArticleBlood2011
Mechanisms of cytotoxicity to Pim kinase inhibitor, SGI-1776, in acute myeloid leukemia.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 161 citations in OpenAlex.
- PIM1 in myeloproliferative neoplasms: potential pathogenic and therapeutic implications.Leukemia · 2026Review
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- Scaffold Hopping-Guided Design of Novel PIM-1 Inhibitors with Anticancer Activities.Molecules (Basel, Switzerland) · 2026Article
- Anthelmintics Derived from the Kinase Inhibitor SGI-1776 for the Treatment of Gastrointestinal Worm Infections.ACS infectious diseases · 2025Article
- Counter-Therapeutic Strategies for Resistance of FLT3 Inhibitors in Acute Myeloid Leukemia.Cells · 2025Review
- Comprehensive Analysis of Clinically Discontinued Compounds Using an In Vitro Secondary Pharmacology Panel to Predict Potential Safety Risks during Drug Development.ACS pharmacology & translational science · 2025Article
- Synthesis of novel pyridine and pyrazolyl pyridine conjugates with potent cytotoxicity against HepG2 cancer cells as PIM-1 kinase inhibitors and caspase activators.RSC advances · 2024Article
- PIM3 Kinase: A Promising Novel Target in Solid Cancers.Cancers · 2024Review
- Exploring the untapped pharmacological potential of imidazopyridazines.RSC advances · 2024Review
- Article
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor.PloS one · 2023Article
- Antitumor activity of the protein kinase inhibitor 1-(β-D-2'-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines.BMC cancer · 2022Article
- Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy.PLoS neglected tropical diseases · 2022Article
- Targeting PIM2 by JP11646 results in significant antitumor effects in solid tumors.International journal of oncology · 2022Article
- PIM1/STAT3 axis: a potential co-targeted therapeutic approach in triple-negative breast cancer.Medical oncology (Northwood, London, England) · 2022Review
- Proviral Integration of Moloney Virus-2 (PIM-2) Expression Level as a Prognostic Marker in Patients with Acute Myeloid Leukemia.International journal of general medicine · 2022Article
- Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021Review
- Engineered Fully Human Single-Chain Monoclonal Antibodies to PIM2 Kinase.Molecules (Basel, Switzerland) · 2021Article
- Imidazopyridazine Acetylcholinesterase Inhibitors Display Potent Anti-Proliferative Effects in the Human Neuroblastoma Cell-Line, IMR-32.Molecules (Basel, Switzerland) · 2021Article
14 more citing papers are in PubMed but not listed here.
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5 authors at 2 institutions in 1 country.
Funding
Abstract
Pim kinases are Ser/Thr kinases with multiple substrates that affect survival pathways. These proteins are overexpressed in acute myeloid leukemia (AML) blasts and we hypothesized that Pim kinase inhibition would affect AML cell survival. Imidazo[1,2-b]pyridazine compound, SGI-1776 inhibits Pim-1, Pim-2 and Pim-3, and was evaluated in AML-cell line, -xenograft model, and -primary blasts. Treatment of AML cells with SGI-1776 results in a concentration-dependent induction of apoptosis and we investigated its effect on Pim kinase functions. Phosphorylation of traditional Pim kinase targets, c-Myc(Ser62) and 4E-BP1 (Thr36/Thr47), were both decreased in actively cycling AML cell lines MV-4-11, MOLM-13 and OCI-AML-3. Levels of antiapoptotic proteins Bcl-2, Bcl-x(L), XIAP, and proapoptotic Bak and Bax were unchanged; however, a significant reduction in Mcl-1 was observed. This was correlated with inhibition of global RNA and protein synthesis and MCL-1 transcript decline after SGI-1776 treatment. These data suggest that SGI-1776 mechanism in AML involves Mcl-1 protein reduction. Consistent with cell line data, xenograft model studies with mice bearing MV-4-11 tumors showed efficacy with SGI-1776. Importantly, SGI-1776 was also cytotoxic in AML primary cells, irrespective of FLT3 mutation status and resulted in Mcl-1 protein decline. Pim kinase inhibition may be a new strategy for AML treatment.
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