AZD1480 / AstraZeneca - LARVOL DELTA

VSIG4 Inhibits Microglia-Mediated Neuroinflammation and Neuronal Injury by Modulating the JAK2-STAT3/NF-κB Signaling Pathway in Parkinson's Disease. (PubMed, Mol Neurobiol) - "Moreover, the addition of AZD1480 attenuated the effects of VSIG4 overexpression both in vitro and in vivo. VSIG4 ameliorates microglia-mediated neuroinflammation and neuronal injury via the JAK2-STAT3/NF-κB pathway in PD, shedding light on its supplementation as a potential treatment option for PD."

Journal • CNS Disorders • Inflammation • Movement Disorders • Oncology • Parkinson's Disease • IL1B • IL6 • TNFA

Multi-cohort integration and machine learning identify CPVL as a novel oncogenic driver in gastric cancer. (PubMed, Discov Oncol) - "Through systematic multi-cohort integration and machine-learning prioritization, CPVL was identified as a novel oncogenic driver in gastric cancer. CPVL promotes tumor growth via activation of the JAK2/STAT3 pathway and regulation of the Cyclin D1/CDK4/p27 axis, highlighting its potential as a diagnostic biomarker and therapeutic target."

Journal • Gastric Cancer • Oncology • Solid Tumor • BCAT1 • CCND1 • CDK4

STAT1 SIGNALING DRIVES MICROENVIRONMENT-MEDIATED VENETOCLAX RESISTANCE AND PROLIFERATION IN CLL (EHA 2026) - "Notably, JAK inhibition (ruxolitinib, AZD1480; Fig.I ) or STAT1 knockout in primary CLL cells (CRISPR; Fig.J ) impaired TME-driven proliferation. JAK inhibition consistently restored venetoclax sensitivity across TME models, providing a strong rationale for combining JAK inhibitors with venetoclax. Supported by the Ministry of Health of the Czech Republic (NU22-03-00117, NW24-03-00369), Czech Science Foundation (25- 15368X), MH CZ-DRO (FNBr,65269705), MUNI/A/1733/2025."

Chronic Lymphocytic Leukemia • BCL2L1 • CD5 • CXCR4 • IFNG • IL21 • IRF1 • MCL1 • STAT1

ETV6::JAK2 FUSION PROMOTES CENTRAL NERVOUS SYSTEM INVASION IN MURINE B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (EHA 2026) - "In vitro treatment of primary leukemic cells with AZD1480 (JAK2 kinase inhibitor) significantly impaired the survival of ETV6::JAK2; Rag2 -/-; Cdkn2a -/- cells but not Rag2 -/-; Cdkn2a -/- cells. Moreover, treatment of Rag2 -/-; Il2rg -/- mice transplanted with ETV6::JAK2-driven B-ALL with FDA-approved JAK1/JAK2 inhibitor Ruxolitinib (50 mg/kg/daily) resulted in significant reduction of circulating B-ALL cells and concomitant increased number of apoptotic cells in the spleen, in comparison to vehicle group...Moreover, transcriptomic analysis of leukemic cells from ETV6::JAK2; Rag2 -/-; Cdkn2a -/- mice revealed upregulation of genes ( Selplg and Ccr5) and signaling pathways (unfolded protein response and cholesterol synthesis) related to CNS invasion in B-ALL, compared to Rag2 -/-; Cdkn2a -/- leukemia. . Summary/Conclusion In conclusion, the ETV6::JAK2 fusion promotes leukemia survival, accelerates disease development, and confers increased neurotropism to leukemic cells."

Preclinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • CDKN2A • ETV6 • IL2RG • JAK2 • PAX5 • PTPRC • STAT5

Resveratrol Alleviates Inflammation in Polycystic Ovary Syndrome by Inhibiting Absent in Melanoma 2 Expression. (PubMed, Phytother Res) - "Notably, LPS-induced upregulation of AIM2 and these inflammatory cytokines was completely reversed by blocking the JAK2/STAT3 pathway using AZD-1480 and SH-4-54, respectively...In conclusion, RES alleviates chronic inflammation in PCOS by inhibiting AIM2 via blocking the JAK2/STAT3 pathway. Our findings suggest that the targeted inhibition of AIM2 could represent a novel therapeutic approach for PCOS."

Journal • Inflammation • Melanoma • Oncology • Polycystic Ovary Syndrome • Solid Tumor • AIM2 • IL1B • IL6

IFN-γ-induced AIM2-PANoptosis in granulosa cells leads to ovulatory dysfunction in polycystic ovary syndrome. (PubMed, Biochem Pharmacol) - "While, blocking IRF1 (using RNA interference-based knockdown), HAS2 (using 4-MU), JAK2 (using AZD-1480), or STAT3 (using SH-4-54) completely abolished these effects...Taken together, our results suggest that AIM2-PANoptosis occurs in the GCs of PCOS and is triggered by the IFN-γ/IRF1/HAS2 signalling pathway, thereby resulting in ovulatory dysfunction. This study therefore provides valuable potential therapeutic targets for the treatment of this typical PCOS symptom."

Journal • Polycystic Ovary Syndrome • CASP3 • IFNG • IL1B • IRF1 • JAK2 • NLRP3 • STAT3

Obesity- and tumor-derived signals drive cancer-associated state transitions in breast mesenchymal stromal/stem cells reprogrammed by IL1RA or JAK inhibition. (PubMed, Exp Hematol Oncol) - "Mechanistically, IL1 receptor blockade (anakinra) or JAK inhibition (AZD1480) reverses both iCAF and myCAF phenotypes and functionally suppresses stromal-driven epithelial-mesenchymal transition as well as cancer stemness in breast cancer cells. These findings establish a mechanistic link between obese cues, stromal plasticity, and breast cancer progression, and reveal IL1/JAK signaling as a tractable axis to therapeutically reprogram the breast cancer stroma."

Journal • Breast Cancer • Genetic Disorders • Obesity • Oncology • Solid Tumor • IL1R1 • TGFB1

Aerobic Exercise Promotes Hippocampal Neurogenesis and Ameliorates Cognitive Dysfunction Induced by Unilateral Labyrinthectomy. (PubMed, CNS Neurosci Ther) - "These findings provide a novel non-pharmacological strategy for cognitive rehabilitation, as well as early cognitive screening and exercise rehabilitation intervention for patients with vestibular disorders."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • Otorhinolaryngology • CD74

Heme Oxygenase-1 Regulates the JAK/STAT Pathway to Inhibit Ferroptosis in Metabolic Dysfunction-Associated Steatotic Liver Disease. (PubMed, J Biochem Mol Toxicol) - "AZD1480 reversed the effects of erastin and improved MASLD. Collectively, our results suggest that HMOX1 protects against MASLD by suppressing ferroptosis through JAK/STAT pathway inhibition."

Journal • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • HMOX1

Aging changes the mechanism that underlies JAK2 modulation of neutrophil function. (PubMed, J Immunol) - "Neutrophils from young (3 mo) and aged (≥22 mo) male and female C57BL/6J mice were isolated, treated with a JAK2 inhibitor (AZD1480) or a pan-JAK inhibitor (baricitinib), and stimulated with PMA. Metabolically, JAK2 enhances pentose phosphate pathway activity in young neutrophils and decreases glycogen breakdown in aged cells. These findings reveal mechanisms by which JAK2 modulates neutrophil function and suggest that organismal age plays a role in this modulation."

Journal • JAK2

ESTABLISHMENT OF A MOLECULARLY INFORMED PRECLINICAL TESTING PLATFORM TO IDENTIFY EFFECTIVE TREATMENTS AND COMBINATIONS FOR PEDIATRIC DOWN SYNDROME ASSOCIATED LEUKEMIA (SIOP 2025) - "JAK inhibitors (Fedratinib, Ruxolitinib, Momelotinib, AZD1480) significantly reduced viability. This preclinical DS-leukemia model enables the identification of targeted therapies and drug combinations to improve clinical outcomes in this vulnerable subgroup of patients. Our findings highlight the JAK/STAT pathway as a key therapeutic target and support a critical role for ABeta-40 in the DS-leukemia microenvironment."

IO biomarker • Preclinical • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Pediatrics • CDC37 • CRLF2 • HSP90AA1 • Plasma Aβ40

Reprogramming cancer-educated adipose stromal cells and impacts on interaction with breast cancer (FIGO 2025) - "Treatments included interleukin-1β inhibitor (anakinra), JAK1/2 inhibitor (AZD-1480), and TGF-β to assess reprogramming and interactions between bASCs and cancer cells. Reprogramming lean and obese aT bASCs reduces EMT. Moreover, it decreased cancer stem cell induction by interfering with the activation of the MYC-signaling pathways, suggesting a viable strategy to modify the TME before conventional therapies. This approach may offer new pathways for improving breast cancer treatment."

Stroma • Breast Cancer • Obesity • Oncology • Solid Tumor • ACTA2 • COL1A1 • COL4A1 • IL1B • TGFB1

IFNγ/IL21-JAK-STAT1 Signaling Axis Drives T-Cell–Mediated CLL Proliferation and Venetoclax Resistance (IWCLL 2025) - "We reveal for the first time that IFNγ and IL21 are the key factors driving CLL cell proliferation and survival in lymph nodes. Both activate STAT1, which we identified as responsible for most gene expression changes in LN-resident CLL cells and their ability to proliferate. Additionally, IFNγ mediates robust venetoclax resistance in CLL, which can be effectively reversed by JAK inhibitors (ruxolitinib or AZD1480), providing a rationale for their combination.Supported by the Ministry of Health of the Czech Republic (grant no."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • BCL2L1 • CD40LG • CD5 • CD8 • CXCL12 • CXCR4 • IFNA1 • IFNG • IL2 • IL21 • IL4 • MCL1 • MIR150 • STAT1 • TNFA

IFNγ/IL21-JAK-STAT1 Signaling Axis Drives T-Cell–Mediated CLL Proliferation and Venetoclax Resistance (IWCLL 2025) - "We reveal for the first time that IFNγ and IL21 are the key factors driving CLL cell proliferation and survival in lymph nodes. Both activate STAT1, which we identified as responsible for most gene expression changes in LN-resident CLL cells and their ability to proliferate. Additionally, IFNγ mediates robust venetoclax resistance in CLL, which can be effectively reversed by JAK inhibitors (ruxolitinib or AZD1480), providing a rationale for their combination.Supported by the Ministry of Health of the Czech Republic (grant no."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • BCL2L1 • CD40LG • CD5 • CD8 • CXCL12 • CXCR4 • IFNA1 • IFNG • IL2 • IL21 • IL4 • MCL1 • MIR150 • STAT1 • TNFA

RBM10 inhibits pancreatic cancer development by suppressing immune escape through PD-1 expression. (PubMed, J Cancer) - "However, treatment with the JAK pathway inhibitor AZD1480 restored NK cell cytotoxicity against cancer cells. Finally, high RBM10 expression was associated with a favourable prognosis in pancreatic cancer patients, suggesting that RBM10 inhibits pancreatic cancer progression by suppressing tumour immune escape through JAK-STAT-mediated regulation of PD-1 expression in NK cells. This finding offers potential for the development of novel precision-targeted therapies in the management of pancreatic cancer."

IO biomarker • Journal • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • JAK1 • JAK2 • PD-1 • RBM10 • STAT3

ETV6::JAK2 fusion promotes central nervous system invasion in murine B-cell acute lymphoblastic leukemia (EACR 2025) - "In vitro treatment of primary leukemic cells with AZD1480 (JAK2 inhibitor) significantly impaired the survival of ETV6::JAK2; Rag2-/-; Cdkn2a-/- cells but not Rag2-/-; Cdkn2a-/- cells. To assess JAK2 signaling dependency in vivo, Rag2-/-; Il2rg-/- mice injected intravenously with ETV6::JAK2-driven B-ALL cells were treated for four days with FDA-approved JAK1/JAK2 inhibitor Ruxolitinib (50 mg/kg/daily) upon detection of ˃ 1% peripheral B-ALL blasts... In conclusion, the ETV6::JAK2 fusion promotes leukemia survival, accelerates disease development, and confers increased neurotropism to leukemic cells."

Preclinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • CASP3 • CDKN2A • ETV6 • IL2RG • JAK2 • PAX5 • PTPRC • STAT5

DEC1 promotes breast cancer bone metastasis through transcriptional activation of CXCR4. (PubMed, J Biomed Res) - "Notably, AMD3100 (a CXCR4 antagonist) partially reversed the DEC1-OE-induced upregulation of CXCR4 and associated pro-metastatic genes...Furthermore, pharmacological inhibition of AKT (LY294002) or JAK2 (AZD1480), but not ERK (PD98059), attenuated DEC1-mediated CXCR4 upregulation, although all three inhibitors mitigated DEC1-driven migration-related gene expression. Additionally, DEC1 enhanced CXCL12 secretion from mesenchymal stromal cells and osteoblasts, amplifying the CXCR4/CXCL12 axis within the bone microenvironment. Collectively, our findings demonstrate that DEC1 promotes breast cancer (BC) bone metastasis by directly transactivating CXCR4 expression, providing a molecular basis for targeting DEC1 to prevent and treat BC bone metastasis."

Journal • Breast Cancer • Oncology • Solid Tumor • CXCL12 • CXCR4 • JAK2

Evaluation of the In Vivo Efficacy of the JAK Inhibitor AZD1480 in Uterine Leiomyomas Using a Patient-derived Xenograft Murine Model. (PubMed, Reprod Sci) - "These findings suggest JAK inhibition as a potential treatment for uterine leiomyomas by targeting angiogenesis. However, further studies are warranted to explore alternative JAK inhibitors, examine downstream effects, optimize dosing, and establish clinical efficacy and safety."

Journal • Preclinical • Oncology • Solid Tumor • Uterine Leiomyoma

Suppression of the JAK/STAT pathway inhibits neuroinflammation in the line 61-PFF mouse model of Parkinson's disease. (PubMed, J Neuroinflammation) - "AZD1480 treatment reduced cell numbers and cluster-specific expression of the antigen-presentation genes H2-Eb1, H2-Aa, H2-Ab1, and Cd74 in the MM4 cluster and proinflammatory genes such as Tnf, Il1b, C1qa, and C1qc in the T3 cluster. Together, these results indicate that inhibiting the JAK/STAT pathway suppresses the activation and infiltration of innate and adaptive cells, reducing neuroinflammation in the Line 61-PFF mouse model."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • C1QA • CD74 • CD8 • IL1B • PTPRC • THY1

Zhiqiao Gancao decoction regulated JAK2/STAT3/ macrophage M1 polarization to ameliorate intervertebral disc degeneration. (PubMed, Heliyon) - "Primary macrophage M1 polarization was induced using LPS, with cells treated using the JAK2 inhibitor (AZD1480) and ZQGCD to evaluate macrophage polarization, cellular supernatant inflammatory factors, and JAK2/STAT3 pathway expression...There is macrophage infiltration in the intervertebral disc tissue of IDD rats, and JAK2/STAT3 pathway is activated, macrophages are polarized to M1 type, resulting in inflammatory microenvironment, leading to intervertebral disc degeneration and hyperalgesia. ZQGCD exhibited a delaying effect on IDD and improved hyperalgesia by inhibiting the JAK2/STAT3/macrophage M1 polarization pathway."

Journal • Pain • IL1B • IL6 • JAK2 • MMP3 • STAT3 • TNFA

Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation. (PubMed, Biochem J) - "We identified 13 compounds - ABT-578, AR-A014418, AZD1480, AZD5363, Idelalisib,  Ipatasertib, LJ1308, PHA-793887, Rapamycin, Ridaforolimus, SMI-4a,  Temsirolimus and Tideglusib - each of which inhibits mTOR signalling or regulators thereof, and blocked constitutive cell death executed by R30E MLKL. Our study implicates mTOR signalling as an auxiliary factor in promoting transport of activated MLKL oligomers to the plasma membrane, where they accumulate into hotspots that permeabilise the lipid bilayer to cause cell death."

IO biomarker • Journal

Oncostatin M promotes osteogenic differentiation of tendon-derived stem cells through the JAK2/STAT3 signalling pathway. (PubMed, J Orthop Surg Res) - "OSM promotes osteogenic differentiation of TDSCs and the JAK2/STAT3 signalling pathway plays an important role."

Journal

OTUB1 Promotes Glioblastoma Growth by Inhibiting the JAK2/STAT1 Signaling Pathway. (PubMed, J Cancer) - "In addition, we added the JAK2 inhibitor AZD1480 to explore the regulation of OTUB1 for JAK2/STAT1 pathway in GBM... Our study reveals a novel mechanism by which OTUB1 inhibits the JAK2/STAT1 signaling pathway. This contributes to a better understanding of OTUB1's role in GBM and provides a potential avenue for targeted therapeutic intervention."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • Targeted Protein Degradation • OTUB1

V-set and immunoglobulin domain containing 4 inhibits oxidative stress, mitochondrial dysfunction, and inflammation to attenuate Parkinson's disease progression by activating the JAK2/STAT3 pathway. (PubMed, J Neuroimmunol) - "VSIG4 suppresses oxidative stress, mitochondrial dysfunction, and inflammation by activating the JAK2/STAT3 pathway, which may be helpful in attenuating PD progression."

Journal • CNS Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Oncology • Parkinson's Disease • IL1B • TNFA

Suppression of the JAK/STAT Pathway Inhibits Neuroinflammation in the Mouse Model of Parkinson's Disease (IMMUNOLOGY 2024) - "AZD1480 treatment reduced cell numbers of the MG2, MM4, and T3 clusters and suppressed the expression of cluster-specific genes, including H2-Aa, H2-Ab1, Cd74, Tnf, Il1b, and C1qc in MM4 and T3. These results indicate that inhibiting the JAK/STAT pathway suppresses the infiltration and activation of specific macrophages and T-cells in our PD model."

Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • CD74 • CD8 • IL1B • PTPRC • THY1