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nilotinib (Danziten)

✓ Approved

Azurity Pharmaceuticals, Inc. · ABL1 · 小分子

什么是 nilotinib？

nilotinib 是一种小分子，由Azurity Pharmaceuticals, Inc.研发。该药已获批，用于治疗相关适应症，给药途径：Oral (PO)。

药物档案

商品名Danziten
公司Azurity Pharmaceuticals, Inc.
药物类别小分子
分子靶点ABL1, BCR, KIT, PDGFRA
给药途径Oral (PO)
状态Approved
来源： ClinicalTrials.gov, Azurity Pharmaceuticals, Inc.

作用机制

分子靶点

nilotinib 作用于 4 个分子靶点：

ABL1ABL proto-oncogene 1, non-receptor tyrosine kinase (c-ABL, bcr/abl)
BCRBCR activator of RhoGEF and GTPase (CML, ALL)
KITKIT proto-oncogene, receptor tyrosine kinase (MASTC, CD117)
PDGFRAplatelet derived growth factor receptor alpha (PDGFR-2, CD140A)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

nilotinib 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Chronic myeloid leukaemia✓ Approved

相关研究文献

PubMedPharmacogenetics and genomics2026-08-02

Association of UGT and CYP genotype-predicted activity with tyrosine kinase inhibitor toxicity.

Moy April T AT, D'Angelo Lia E LE, Hertz Daniel L DL

Associations between genetically predicted activity of metabolic enzymes and risks of adverse events from tyrosine kinase inhibitors (TKIs) may inform dosing to optimize treatment outcomes in patients with cancer. The goal of this study is to investigate the associations between UGT1A1, CYP3A4, and CYP1A2 activity and toxicity from nilotinib and pazopanib treatment. A retrospective pharmacogenetic association study was conducted in 117 participants of the Michigan Genomics Initiative who received pazopanib (n = 103) or nilotinib (n = 14). Clinical information, including patients' disease, treatment, and toxicity was collected via retrospective review of medical records. No associations were found between the genetically predicted activity of any of the three enzymes and the composite endpoint of severe toxicity or treatment modifications because of toxicity. In the secondary hypothesis-generating analyses, patients with reduced UGT1A1 activity had an increased incidence of increased aspartate aminotransferase/alanine aminotransferase (44 vs. 25%; P = 0.034) and hypertension (52 vs. 31%; P = 0.024). In addition, patients with increased CYP1A2 activity from carrying CYP1A2*1F had a lower incidence of severe toxicity from pazopanib (β-coefficient = -0.163, 95% confidence interval: -0.19 to -0.14, P = 0.008). Future investigations are needed to confirm these associations and determine whether personalized TKI treatment can optimize therapeutic outcomes in patients with cancer.

PMID 42542560
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PubMedNeuro-oncology advances2026-07-31

Membrane proteomic profiling to identify candidate therapy targets for glioblastoma infiltration.

Porter Harry H, Mulhall Kayley K, Shah Maria M, Vinohar Jeffy Joseph JJ et al.

Glioblastoma (GBM) is an aggressive brain tumor characterized by rapid growth and infiltration. New therapies are desperately needed to improve GBM patient outcomes. Intra-tumoral heterogeneity is a common driver of failure for novel GBM treatments, and many preclinical studies rely on cell lines established from the tumor core. As a result, they fail to characterize the infiltrative tumor cells, which remain post-surgery and ultimately drive tumor recurrence. This study characterizes the membrane proteome of 3 patient-derived GBM cell lines isolated from the tumor invasive margin (GIN8, GIN28, and GIN31), which is a proxy for residual disease post-surgery. We combined plasma membrane protein analysis with total protein analysis using liquid chromatography-mass spectrometry to uncover therapeutic targets most amenable for drug repurposing. Molecular docking analysis predicted specific binding pockets on the surface of key membrane proteins against which the top 10 approved drug candidates were screened based on their binding energy scores. Membrane proteins such as EDIL3, DYSF, ROBO1, SERPINE2, LOXL1, and CD70 were consistently significantly upregulated across GBM cell lines relative to healthy astrocyte controls, indicating potential functional roles in GBM progression. Molecular docking identified nilotinib (targeting LOXL1) and darifenacin (targeting SH3KBP1) as candidate drugs that can bind to identified membrane proteins. Nilotinib and darifenacin produced average IC50 values of 8.45 µM and 46.77 µM, respectively, in cell viability assays against GIN cell lines. These findings suggest that targeting membrane proteins offers promise for developing effective GBM therapies predicated on the most prognostically relevant intra-tumor region.

PMID 42534387
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PubMedFrontiers in oncology2026-07-30

Treatment patterns and outcomes of tyrosine kinase inhibitors in chronic myeloid leukemia: a single center study from Oman.

Al-Rawahi Noor N, Salman Bushra B, Meenakshi Dhanalekshmi Unnikrishnan DU, Al-Khabori Murtadha M et al.

Real-world data on tyrosine kinase inhibitor (TKI) use in chronic myeloid leukemia (CML) from the Middle East remain limited. We evaluated treatment patterns, molecular responses, treatment-free remission (TFR), and safety among Omani patients with chronic-phase CML. In this retrospective single-center study, adult patients (≥18 years) with chronic-phase CML treated with TKIs between January 2008 and September 2024 were included. Demographics, Sokal risk, treatment lines, molecular responses, TFR, and adverse drug reactions (ADRs) were analyzed. Among 112 patients (mean age 43.7 ± 15.4 years), 45% had low Sokal risk, 43% intermediate, and 12% high risk. Imatinib was first-line therapy in 88.4%, achieving major molecular response (MMR) in 51%, with a median time to MMR of 21 months. In contrast, second-line TKIs demonstrated higher efficacy, with MMR rates of 79.2% for nilotinib and 54.4% for dasatinib, and shorter time to response (12 vs 23.2 months, respectively). Successful TFR was maintained in 17% of imatinib-treated patients after two years and in 83.3% of second-line patients after 36 months. ADRs were mainly gastrointestinal (28.5%), musculoskeletal (28.0%), dermatologic (20.8%), and hematologic (8.7%). Grade 3-4 events occurred in 5%, leading to TKI switching. Discontinuations were primarily due to loss of response, ADRs, or planned TFR. In this real-world cohort, first-line imatinib provided acceptable but slower and less frequent molecular responses compared with second-generation TKIs. Higher TFR maintenance rates were observed with second-generation TKIs, although interpretation is limited by small patient numbers. These findings support a response-guided, risk-adapted approach to TKI selection and highlight the need to expand access to second-generation TKIs to optimize long-term outcomes in CML.

PMID 42528802
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PubMedBiochemical and biophysical research communications2026-07-25

Exploring the therapeutic potential of NCX1 in hematological cancers; integration of molecular docking, bioinformatics approaches, and experimental validation.

Misir Sema S, Yaman Serap Ozer SO, Petrović Nina N, Cakmak Isik I et al.

Hematological malignancies are highly heterogeneous diseases characterized by dysregulated signaling pathways and limited durable therapeutic responses. Calcium homeostasis has emerged as a critical regulator of cancer cell fate, yet the role of the sodium/calcium exchanger 1 (NCX1/SLC8A1) in leukemogenesis remains poorly defined. In this study, we comprehensively investigated the biological significance and therapeutic potential of NCX1 across major hematological malignancies by integrating transcriptomic analyses, protein-protein interaction networks, experimental validation, and in silico drug repurposing strategies. NCX1 was highly expressed in HL-60, K-562, and Jurkat cells compared to HaCaT controls. Network analyses revealed that NCX1 interacts with key regulators of calcium signaling, immune response, and signal transduction. In AML and CML patient datasets, a strong positive correlation was observed between NCX1 expression and immune-related pathways, while a negative correlation was observed with translation-related processes. Molecular docking analyses demonstrated that several clinically approved compounds, particularly imatinib and nilotinib, interact with NCX1. Molecular dynamics simulation was performed to evaluate the binding stability and safety of imatinib. Remarkably, the comprehensive analysis showed that imatinib exhibited a stable molecular dynamics profile. All these findings have demonstrated NCX1 as a biologically informative marker of myeloid differentiation and a promising therapeutic weak point within calcium signaling networks in hematological malignancies, providing a rationale for future functional and single-cell validation studies.

PMID 42497834
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PubMedCell reports. Medicine2026-07-23

Nilotinib induces immunogenic cuproptosis to potentiate cancer immunotherapy.

Yao Lei L, Zhao Deze D, Meng Yu Y, Liu Yihuang Y et al.

Immunotherapy efficacy is limited by poor tumor immunogenicity and insufficient immune infiltration, highlighting the critical role of inducing immunogenic cell death for improved outcomes. Targeting cuproptosis holds promising therapeutic potential, but its immunogenic and capacity to stimulate anti-tumor immunity to potentiate immunotherapy remains unknown. Through screening of 240 Food and Drug Administration (FDA)-approved anti-tumor drugs, we identify nilotinib as a potent cuproptosis inducer in cancer cells, especially at physiologically relevant copper concentrations. Mechanistically, nilotinib-copper elicits cuproptosis in vitro and in vivo by repressing the copper exporter ATP7A via ETV1 to drive mitochondrial copper accumulation and activating mitogen-activated protein kinase (MAPK) pathway through ERK2 phosphorylation. Preclinically, nilotinib-copper induces immunogenic cuproptosis and enhances anti-PD-1 efficacy across multiple melanoma models, including B16F10 tumor-bearing mice, Braf/Pten-driven spontaneous melanoma mice, and PBMC-humanized mice. Clinically, the ATP7ALow/MAPKHigh signature correlates with improved immunotherapy response and prolonged overall survival. This work establishes nilotinib as a clinically tractable, non-ionophore immunogenic cuproptosis inducer capable of activating anti-tumor immunity to potentiate immunotherapy.

PMID 42486098
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PubMedEuropean journal of haematology2026-07-23

Diabetic Patients With Newly Diagnosed Chronic Myeloid Leukemia: TKI Choice and Early Adverse Events. A Real-Life Survey Within the Italian Chronic Myeloid Leukemia Network.

Russo S S, Capodanno I I, Tiribelli M M, Miggiano M C MC et al.

Limited data are available regarding patients with newly diagnosed chronic myeloid leukemia (CML) and concomitant diabetes mellitus (DM). Hence, we retrospectively analyzed 2149 patients with newly diagnosed chronic phase (CP) CML to compare clinical characteristics, choice of frontline therapy, early adverse events, and molecular responses between patients with or without DM. Among this cohort of 2149 patients, 241 patients (11.2%) had DM at CML diagnosis. Diabetic patients were older (median age 69.6 vs. 58.2 years, p < 0.001), showed a higher Sokal/ELTS risk and had more comorbidities, resulting in more frequent polypharmacy. Imatinib was frequently selected as first-line treatment in diabetic patients (71% vs. 53%, p < 0.001), whereas nilotinib was more common in nondiabetics (6.2% vs. 31.9%). Discontinuation by the 12th month occurred in 24.2% of diabetic patients versus 19.4% of nondiabetics (p = 0.031), mainly for hematologic toxicity. Diabetic patients showed a lower incidence of major molecular response (MMR) at the 12th month (55.9% vs. 68.1%, p = 0.002). Among diabetic patients, a trend toward better molecular responses was observed in patients receiving metformin (p = 0.068). In conclusion, DM represents a clinically meaningful comorbidity in newly diagnosed CML-CP, and seems to define a subgroup with distinct features, influencing both treatment decisions and early outcomes.

PMID 42486531
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