ArticleBlood2009
Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 198 citations in OpenAlex.
- PIM1 in myeloproliferative neoplasms: potential pathogenic and therapeutic implications.Leukemia · 2026Review
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- Long-acting IL-7 induces distinct transcriptomic features in peripheral T cells of patients with solid tumors.JCI insight · 2026Article
- FromRSC advances · 2026Article
- PIM1 Inhibition Alleviates Aspergillus fumigatus Keratitis by Regulating DDX41-Mediated STING Signaling Pathway.Investigative ophthalmology & visual science · 2026Article
- Synergistic apoptosis induction in myelodysplastic syndrome cells by azacitidine and PIM-2 inhibitors via nuclear factor-kappa B pathway inhibition.BMC cancer · 2026Article
- Anthelmintics Derived from the Kinase Inhibitor SGI-1776 for the Treatment of Gastrointestinal Worm Infections.ACS infectious diseases · 2025Article
- Discovery and Characterization of Novel PIM1 Inhibitors via Virtual Screening and Molecular Dynamics Simulations.ACS medicinal chemistry letters · 2025Article
- 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
- Cohesin-mediated stabilization of the CCAN complex at kinetochores in mitosis.Current biology : CB · 2025Article
- PIM1 kinase and its diverse substrate in solid tumors.Cell communication and signaling : CCS · 2024Review
- A promising natural product in diffuse large B-cell lymphoma therapy by targeting PIM1.Annals of hematology · 2024Article
- S100A8/A9 predicts response to PIM kinase and PD-1/PD-L1 inhibition in triple-negative breast cancer mouse models.Communications medicine · 2024Article
- PIM1 targeted degradation prevents the emergence of chemoresistance in prostate cancer.Cell chemical biology · 2024Article
- PIM3 Kinase: A Promising Novel Target in Solid Cancers.Cancers · 2024Review
- An overview of pim kinase as a target in multiple myeloma.Cancer medicine · 2023Review
- When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases.International journal of molecular sciences · 2023Review
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy.PLoS neglected tropical diseases · 2022Article
- Synergistic PIM kinase and proteasome inhibition as a therapeutic strategy for MYC-overexpressing triple-negative breast cancer.Cell chemical biology · 2022Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Pim kinases are involved in B-cell development and are overexpressed in B-cell chronic lymphocytic leukemia (CLL). We hypothesized that Pim kinase inhibition would affect B-cell survival. Identified from a screen of imidazo[1,2-b]pyridazine compounds, SGI-1776 inhibits Pim-1, Pim-2, and Pim-3. Treatment of CLL cells with SGI-1776 results in a concentration-dependent induction of apoptosis. To elucidate its mechanism of action, we evaluated the effect of SGI-1776 on Pim kinase function. Unlike in replicating cells, phosphorylation of traditional Pim-1 kinase targets, phospho-Bad (Ser112) and histone H3 (Ser10), and cell-cycle proteins were unaffected by SGI-1776, suggesting an alternative mechanism in CLL. Protein levels of total c-Myc as well as phospho-c-Myc(Ser62), a Pim-1 target site, were decreased after SGI-1776 treatment. 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 that was not caused by caspase-mediated cleavage of Mcl-1 protein. The mechanism of decline in Mcl-1 was at the RNA level and was correlated with inhibition of global RNA synthesis. Consistent with a decline in new RNA synthesis, MCL-1 transcript levels were decreased after treatment with SGI-1776. These data suggest that SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction.
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Registered trials
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.