AZD1208 / AstraZeneca - LARVOL DELTA

Neutrophil membrane-coated and MMP2-responsive nanoparticles deliver PIM1 inhibitor to alleviate inflammatory arthritis through inhibiting Th17 cell differentiation. (PubMed, J Nanobiotechnology) - "These results suggested that NM@MRP-NP was a structurally defined, biologically stable, inflammatory-targeted and conditionally releasing nanotherapeutic system with efficient drug delivery, which could provide new insight into the targeted interventions for IA."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatology • CD4 • MMP2

Pim1 Serves as a Therapeutic Target for Inflammatory Arthritis via Mitochondrial Metabolism and Th17 Cell Differentiation. (PubMed, Research (Wash D C)) - "Conditional knockdown of Pim1 in CD4+ T cells (Pim1 cKO) or using the Pim1 inhibitor AZD1208 alleviated the development of inflammatory arthritis in association with decreasing the proportion of Th17 cells. Through molecular docking and dynamic simulation, nilotinib, a Food-and-Drug-Administration-approved drug, was identified as a selective substitute for the currently clinically nonapproved Pim1 inhibitors, which impeded Th17 cell differentiation and was well tolerated during the treatment of Pim1 cKO mice and 2 inflammatory arthritis mouse models. Our study contributes to a better understanding of the mechanism through which Pim1 promotes Th17 cell differentiation and advances the clinical application of Pim1 as an effective target for treating inflammatory arthritis."

Journal • Ankylosing Spondylitis • Hematological Malignancies • Immunology • Inflammatory Arthritis • Leukemia • Oncology • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CD4 • PIM1

THE PIM AND ATK KINASES COOPERATIVELY SUPPORT LUNG MYOFIBROBLAST ACTIVATION IN SSC BY REGULATING ENERGY AND PROTEIN METABOLISM (SSWC 2026) - "For the bleomycin model, mice were dosed with AZD1208 via oral gavage, 5 days a week for 3 weeks starting 1 day before the bleomycin challenge (prophylactic) or for 2 weeks starting at 7 days after bleomycin challenge (therapeutic). We propose that PIM and ATM act cooperatively to maintain high levels of amino acid and energy production, and both must be blocked to starve fibroblasts of the raw materials and energy needed to continue to lay down and expand fibrotic tissue. Combined PIM and ATM inhibition may be a novel way to slow or stop fibrotic disease progression."

Fibrosis • EIF4EBP1 • TGFB1

Unraveling the role of host kinase PIM1 in Toxoplasma gondii infection: Implications for therapies. (PubMed, PLoS Negl Trop Dis) - "Our findings underscore the necessity of PIM1's kinase activity in this process, as evidenced by the significant reduction in T. gondii proliferation upon treatment with either a kinase-dead PIM1 mutant or the PIM1 inhibitor AZD1208...Collectively, our findings illuminate host-parasite interplay during acute toxoplasmosis and position PIM1 as a promising target for anti-T. gondii therapeutics."

Journal • Infectious Disease • PIM1

In Silico Identification of Lepiotaprocerin C as a Promising PIM-1 Kinase Inhibitor: An Integrated Docking, Molecular Dynamics, MM/PBSA, QSAR, and ADMET Study. (PubMed, Bioinform Biol Insights) - "Molecular docking of 12 Lepiotaprocerins revealed Lepiotaprocerin C as the most potent compound, exhibiting superior binding affinity (-11.4 kcal/mol) compared with the reference inhibitor AZD1208...Prediction of Activity Spectra for Substances and toxicity predictions further revealed high antineoplastic potential (Pa = 0.881) and a nontoxic safety profile. These results highlight Lepiotaprocerin C as a promising, stable, and safe inhibitor of PIM-1 kinase, warranting further in vitro and in vivo validation for potential anticancer drug development."

Journal • Hematological Malignancies • Leukemia • Oncology • PIM1

PIM2-dependent modulation of mitochondrial mass and function in multiple myeloma (ASH 2025) - "We hypothesize that PIM2 has anunexplored role in modulating mitochondrial biogenesis to maintain survival of MM cells.We employed PIM2 molecular manipulation: overexpression (OE) of wild type (WT) or kinase dead (K61A)and knockdown (with siRNA or doxycycline-inducible shRNA-ishPIM2) as well as pharmacologicalinhibition of PIM2 protein level and activity, in MM cell lines...LoweringPIM2 protein expression (JP11646; 30 mg/kg by oral gavage) in Vk*myc tail vein injected mouse myelomamodel significantly decreased disease progression in as little as 21 days, while AZD1208 treatment wasnot significantly changing mouse IgG levels when compared with vehicle treatment...Together, these results suggest a KI role of PIM2, in mitochondria biogenesis.Moreover, the anti-survival effects resulted from PIM2 protein degradation in MM cells, might be partiallyattributed to inhibition of mitochondrial biogenesis. Thus, what sustains the functionality and metabolicintegrity of MM..."

IO biomarker • Hematological Malignancies • Monoclonal Gammopathy • Multiple Myeloma • Targeted Protein Degradation • LONP1 • MYC • NRF1 • PIM2 • PPARGC1A • TFAM

PIM1 induces hypoxia-related fibroblast senescence in a mouse model of stress urinary incontinence. (PubMed, PLoS One) - "This study identifies PIM1 as a critical mediator linking hypoxia-induced cellular senescence to the development of SUI. The PIM1 inhibitor AZD-1208 demonstrates promising therapeutic effects, offering a novel approach for the treatment of SUI, with particular relevance for postpartum prevention. These findings elucidate a comprehensive hypoxia-PIM1-senescence pathogenic pathway and identify a potential target for clinical intervention."

Journal • Preclinical • Urinary Incontinence • Urology • CDKN1A • HIF1A • PIM1

Unraveling the Kinase-Independent Autoregulatory Mechanism of PIM2 in Multiple Myeloma (ASH 2024) - "While ATP-competitive PIM2 kinase inhibitors have shown limited efficacy in clinical trials, our laboratory has recently developed and reported on JP11646 (JP1), a first-in-class PIM2-selective non-ATP competitive inhibitor (JR Nair, 2017)...PIM2 promoter activity was measured using luciferase assays with PIM2 Ki inhibitors (JP1, JP2) and a kinase-dependent (Kdep) inhibitor (AZD1208)...SP1 inhibition with terameprocol (TMP) decreased PIM2 protein levels, as shown by Western blot analysis...The identification of specific regulatory elements governing PIM2 Ki autoregulation reveals a new vulnerability in MM that may be exploited for treatment. Further investigation of this complex regulatory network may lead to innovative strategies for targeting PIM2 overexpression in MM therapy."

Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology • Solid Tumor • Targeted Protein Degradation • MYC • PIM1 • PIM3

Pim Kinases Promote Fatty Acid Uptake in Human Neuroblastoma (Quick-Shot) (ACS-CLINCON 2025) - "SK-N-AS and SK-N-BE(2) human neuroblastoma cells were treated for 48 hours with PIM inhibitors (AZD1208 or SGI-1776) or transfected with siRNA targeting PIM1... These results indicate that PIM kinases promote fatty acid uptake in neuroblastoma. As fatty acid uptake regulates pro-tumorigenic processes, PIM inhibition may be useful as a novel therapeutic strategy for neuroblastoma."

Metabolic Disorders • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • PIM1

LILRB4 Protects Multiple Myeloma Cells from Ferroptosis to Promote MM Progression (IMS 2025) - "Importantly, treatment with the PIM inhibitor AZD1208 abrogated the proliferative advantage conferred by LILRB4 overexpression. In conclusion, LILRB4 is highly associated with poor prognosis of MM patients and has the ability of tumorigenesis. LILRB4 promotes MM cell proliferation through STAT3/PIM1 signaling pathway and protects MM cells from ferroptosis, which plays critical roles in MM pathogenesis."

IO biomarker • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • GPX4 • LILRB4 • PIM1

PIM1 Attenuates Innate Immunity to Foster Coronavirus Replication through Ubiquitin Ligase β-TrCP-Mediated IFNAR1 Degradation. (PubMed, Adv Sci (Weinh)) - "Both pan-inhibitors (CX-6528, SGI-1776, AZD-1208) and a specific inhibitor of PIM1 kinase (PIM1 inhibitor 2) effectively block this process and potently inhibit viral replication. This studies demonstrate a novel strategy that viruses use to disrupt cellular innate immunity, suggesting a potential therapeutic target for further anti-virus drug development."

Journal • Infectious Disease • Novel Coronavirus Disease • Targeted Protein Degradation • IFNAR1 • IFNAR2 • PIM1

Novel Autoregulation of PIM2 Expression Sustains Plasma Cell Survival in Multiple Myeloma (IMMUNOLOGY 2025) - "Using PIM2-selective inhibitors, JP11646 (targeting both functions), CpdA (kinase-independent), and AZD1208 (kinase-dependent), we show a novel PIM2 autoregulatory paradigm. Our findings reveal that PIM2 maintains its own expression through kinase-independent transcriptional control while promoting cell survival through kinase-dependent pathways, establishing a novel circuit in malignant plasma cells. This work provides fundamental insights into immune cell gene regulation and suggests innovative therapeutic strategies targeting the dual functions of PIM2 in MM.Keywords: Cells B Cells; Molecules Protein Kinases/Phosphatases Transcription Factors; Processes Gene Regulation; Techniques/Approaches Molecular Biology"

Hematological Malignancies • Multiple Myeloma • Oncology • PIM2

Valosin-Containing Protein (VCP/p97) Mediates Neuroendocrine Differentiation in Prostate Cancer Cells Through Pim1 Signaling Inducing Autophagy. (PubMed, Prostate) - "VCP drives NED in PCa cells through a complex interplay involving the Pim1 axis and autophagy pathways. These findings highlight the potential of targeting VCP/p97 and its associated mechanisms as therapeutic strategies to inhibit NED progression."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • IL6 • MYC • PIM1 • SQSTM1 • STK11 • VCP

Dual Targeting of Pim and PI3 Kinases in Mature T-Cell Lymphoma. (PubMed, Eur J Haematol) - "Strikingly, IBL-202 strongly induced cell-cycle-dependent cell death in cell lines of different mTCL subtypes. Together, our study provides mechanistic evidence supporting a therapeutic strategy of dual Pim- and PI3-kinase inhibition in mature T-cell lymphoma."

Journal • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • BCL2L1

Targeting of PIM Kinases Shows Single Agent Efficacy and Synergizes With BCL2 Inhibitors in Diffuse Large B Cell Lymphoma of the ABC Subtype. (PubMed, Hematol Oncol) - "The combination of AZD1208 with the clinically available BCL2 inhibitor venetoclax was synergistic in most DLBCL cell lines, and this combination induced apoptosis and reduced levels of AKT and MCL1 proteins. These combinations may enable lower doses of PIM inhibitors, leading to increased tolerability and improved anti-tumor activity in clinical settings. The study also highlighted the potential for targeting PIM kinases in combination with other therapies to overcome drug resistance in DLBCL."

Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MCL1 • PIM1

PIM1 inhibition: a novel therapeutic approach for IDH-mutant gliomas (SNO 2024) - "A pan-PIM inhibitor, AZD1208 significantly suppressed cell viability, cell proliferation, and colony formation in IDH-mutant cells but had a lesser effect in IDH-wildtype cells... m6A RNA modification contributes to an enhanced PIM1 activity and thereby a selective sensitivity to PIM1 inhibition in IDH-mutant gliomas."

Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • FTO • YTHDF1

PIM1 inhibition: a novel therapeutic approach for IDH-mutant gliomas (SNO 2024) - "A pan-PIM inhibitor, AZD1208 significantly suppressed cell viability, cell proliferation, and colony formation in IDH-mutant cells but had a lesser effect in IDH-wildtype cells... m6A RNA modification contributes to an enhanced PIM1 activity and thereby a selective sensitivity to PIM1 inhibition in IDH-mutant gliomas."

Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • FTO • YTHDF1

Elucidating the Kinase-Independent Autoregulatory Loop of PIM2 in Multiple Myeloma (IMW 2024) - "Luciferase assays were performed using the full-length PIM2 promoter to assess transcriptional activity in response to PIM2 Ki inhibitors (JP1 and JP2) and a PIM2 kinase-dependent (Kdep) inhibitor (AZD1208)... Our preliminary data support the hypothesis of a novel PIM2 kinase-independent autoregulatory mechanism involving MYC and SP1 in MM. Disruption of this potential PIM2 Ki autoregulatory loop using selective inhibitors (JP1 and JP2) decreases PIM2 expression and promoter activity, suggesting it as a potential therapeutic target. Further investigation into the specific cis-regulatory elements and binding sites governing PIM2 Ki autoregulation may uncover new vulnerabilities to exploit in MM treatment."

Hematological Malignancies • Multiple Myeloma • Oncology

PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy. (PubMed, Curr Top Med Chem) - "A few small chemical inhibitors (E.g., SGI-1776, AZD1208, LGH447) that specifically target the PIM proteins' adenosine triphosphate (ATP)-binding domain have been identified. We explore the involvement of oncogenic transcription factor c-Mycandmi-RNA in relation to PIM kinase. In this article, we highlight the oncogenic effects, and structural insights into PIM kinase inhibitors for the treatment of cancer."

Journal • Hematological Malignancies • Leukemia • Oncology • PIM1

Inhibition of Pim kinases triggers a broad antiviral activity by affecting innate immunity and via the PI3K-Akt-mTOR axis the endolysosomal system. (PubMed, Antiviral Res) - "The pan-Pim kinase inhibitor AZD1208 exerted an extraordinarily high antiviral effect against various ZIKV isolates, SARS-CoV-2) and HBV...We identified Pim-kinases as cellular target for a broad antiviral activity. The antiviral effect exerted by inhibition of Pim-kinases is based on at least two pillars: innate immunity and modulation of the endolysosomal system."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • FGFR1

Optical coherence tomography for multicellular tumor spheroid category recognition and drug screening classification via multi-spatial-superficial-parameter and machine learning. (PubMed, Biomed Opt Express) - "Our results indicated that the effective features combined with supervised learning models successfully classify OVCAR-8 MCTS culturing with 5,000 and 50,000 cell numbers, MCTS with pancreatic tumor cells (Panc02-H7) culturing with the ratio of 0%, 33%, 50%, and 67% of fibroblasts, and OVCAR-4 MCTS treated by 2-methoxyestradiol, AZD1208, and R-ketorolac with concentrations of 1, 10, and 25 µM. This approach holds promise for obtaining multi-dimensional physiological and functional evaluations for using OCT and MCTS in anticancer studies."

Journal • Machine learning • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

First reported PIM kinase degraders: Design, profiling & optimization (AACR 2024) - "The first generation of PIM inhibitors to make it to the clinic, including SGI-1776, AZD1208 and PIM447, are known to be pan-PIM inhibitors, while the aim of this project was to identify novel & selective PIM3 inhibitors. This comprehensive screening cascade ensures an in-depth characterization and optimization of protein degraders, with the possibility of monitoring the ternary complex formation with biophysics methods. It is a good illustration of how this combination of tests can be instrumental in selecting the best degraders to progress to the next step of drug discovery."

Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Solid Tumor • CRBN • DDB1 • FLT3 • JAK2 • PIM1 • PIM3

Prognostic Model Construction of Disulfidptosis-Related Genes and Targeted Anticancer Drug Research in Pancreatic Cancer. (PubMed, Mol Biotechnol) - "Furthermore, through computational biology approaches, the drug AZD1208 was identified as a potential treatment targeting the PPARG protein for pancreatic cancer. This discovery opens new avenues for exploring targets and screening drugs for pancreatic cancer."

Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • PPARG

PIM Kinase Inhibition Sensitizes Neuroblastoma to Doxorubicin. (PubMed, J Pediatr Surg) - "The correlation between PIM and ABCC1 gene expression suggests PIM kinases may contribute to neuroblastoma chemotherapeutic resistance. PIM kinase inhibition increased intracellular doxorubicin accumulation. Combination treatment with AZD1208 and doxorubicin decreased neuroblastoma cell viability in a synergistic fashion. These findings support further investigations of PIM kinase inhibition in neuroblastoma."

Journal • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • ABCC1 • PIM1 • PIM3

Pim kinase inhibitors increase gilteritinib cytotoxicity in FLT3-ITD acute myeloid leukemia through GSK-3β activation and c-Myc and Mcl-1 proteasomal degradation. (PubMed, Cancer Res Commun) - "Cytotoxicity, apoptosis and protein expression and turnover were measured in FLT3-ITD-expressing cell lines and AML patient blasts treated with the FLT3 inhibitor gilteritinib and/or the Pim inhibitors AZD1208 or TP-3654. The data are consistent with c-Myc T58 and Mcl-1 S159 phosphorylation by activated GSK-3β as the mechanism of action of gilteritinib and Pim inhibitor combination treatment, further supporting GSK-3β activation as a therapeutic strategy in FLT3-ITD AML.  ."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • FLT3 • MCL1 • MYC • PIM1 • STAT5