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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

PubMedAsian Pacific journal of cancer prevention : APJCP2026-10-27

Profiling Tyrosine Kinase Inhibitor-Specific Signatures of Homocysteine Metabolism and Mineral Homeostasis in Chronic Myeloid Leukemia.

Abdulla Kawakeb N KN, Hade Istikrar M IM, Jumaa Azal Hamoody AH, Hussein Shallal Murad SM et al.

The application of tyrosine kinase inhibitors (TKIs) has revolutionized the management of chronic myeloid leukemia (CML), rendering it a controllable disease. However, long-term administration is associated with adverse metabolic effects, particularly disruptions in homocysteine metabolism and mineral balance. A comprehensive comparison across TKI types remains absent. This study systematically characterized and compared the metabolic signatures elicited by first- and second-generation TKIs Imatinib, Nilotinib, and Dasatinib on homocysteine and mineral parameters in chronic myeloid leukemia. This retrospective cross-sectional study involved 90 stable CML patients treated with TKI therapy for at least six months at Baghdad Oncology Teaching Hospital between March 2024 and April 2025. Patients were divided into three equal groups based on their medication: Imatinib, Nilotinib, or Dasatinib. Fasting blood samples were collected and analyzed for homocysteine, PTH, calcium, potassium, creatinine, vitamin B12, and ALP. Statistical methods, including ANOVA and correlation analyses, were used to compare groups and explore drug-specific effects. The three TKI groups demonstrated distinct metabolic disturbance patterns. Nilotinib was associated with the highest homocysteine levels and showed strong positive correlations with PTH and ALP. Dasatinib caused a moderate elevation in homocysteine and uniquely correlated positively with potassium. Imatinib showed the most favorable homocysteine profile, which was primarily inversely correlated with calcium. Multivariate analysis confirmed that these metabolic profiles effectively distinguished the three TKI groups. The present study demonstrates that Imatinib, Nilotinib, and Dasatinib elicit distinct and discernible metabolic signatures. These results support the adoption of personalized, TKI-specific monitoring approaches in the management of CML, aiming to proactively reduce long-term cardiovascular and skeletal adverse effects and thereby improve alignment between the quality and duration of survival.

PMID 42935068
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PubMedInternational journal of molecular sciences2026-10-27

Molecular Dynamics-Guided Triage of Approved Drugs Against Escherichia coli Resistance Targets Nominates Capmatinib, Metergoline and Nilotinib as Candidates for Experimental Testing.

Abdelsayed Mena M, Boulaamane Yassir Y

Virtual screening ranks compounds by scoring functions that correlate with molecular size, and hit lists are rarely benchmarked against compounds of established activity. We screened 2070 approved drugs against four Escherichia coli targets selected by pocket-druggability triage (FabI, LpxC, DHFR and GyrB), with each docking protocol validated by redocking its native ligand (RMSD 0.50-0.69 Å). Per target, the two top-scoring compounds and a reference inhibitor were simulated for 100 ns in triplicate (12 complexes, 3.6 μs). Docking did not recover the references: trimethoprim ranked 762/2068 and novobiocin 576/2069, while top-ranked compounds were large, promiscuous drugs recurring across unrelated targets. Pose triage failed, too: all twelve complexes retained 43-87% of initial contacts, contact-loss time separated targets, not compounds, and MM-GBSA favoured the reference at one target of four. Persistent hydrogen bonding separated the reference from the hits at three of four targets, by 2-9-fold, although the GyrB result rests largely on one replicate. Benchmarking each hit against its reference nominates three candidates for experimental testing: capmatinib at DHFR, metergoline at FabI and nilotinib at LpxC. Capmatinib ranks highest on these computational criteria, with the highest pocket retention (87%) and an MM-GBSA energy with no detectable difference from trimethoprim's at n = 3 (absence of evidence for a difference, not evidence of equivalence). In this small panel, carrying a known active through the same pipeline was therefore more informative than docking score, pose stability or end-point rescoring. The nominations are hypotheses: no experimental validation was performed, and generality would require multiple actives and property-matched decoys per target.

PMID 42941792
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PubMedCancer reports (Hoboken, N.J.)2026-10-25

Sequential Philadelphia-Positive Pre-B Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia With Distinct BCR::ABL1 Fusion Transcripts.

Latifi Atbin A, Yousefian Sina S

The sequential emergence of chronic myeloid leukemia (CML) following Philadelphia-positive acute lymphoblastic leukemia (ALL) is exceedingly rare, and its biological basis remains uncertain. We report a 15-year-old boy initially diagnosed at age 4 with Philadelphia-positive pre-B ALL expressing p190 BCR::ABL1. He achieved deep molecular remission following chemotherapy per the COG AALL0232-based high-risk B-ALL protocol plus imatinib. Approximately 5 years after his last documented follow-up, he re-presented with splenomegaly, leukocytosis, anemia, and thrombocytosis. Bone marrow findings supported chronic-phase CML, confirmed by detection of BCR::ABL1 p210 (b2a2 and b3a2) with no detectable p190. Responses to imatinib and dasatinib were suboptimal, and kinase-domain analysis identified a rare ABL1 c.1159T>A (p.Leu387Met) variant. He subsequently underwent matched-related allogeneic hematopoietic stem cell transplantation and remains BCR::ABL1-negative on nilotinib. This case expands the spectrum of sequential Philadelphia-positive leukemias by documenting p190-positive pre-B ALL followed by p210-positive chronic-phase CML, accompanied by detection of the rare L387M variant and suboptimal responses to imatinib and dasatinib. The biological relationship between the two Philadelphia-positive malignancies remains uncertain, with possible explanations including evolution from a shared Philadelphia-positive precursor, therapy-related leukemogenesis, or an independent second malignancy. This case provides unique insight into the biological complexity of sequential Philadelphia-positive leukemias and adds to the evolving literature regarding the clinical significance of the L387M variant in TKI response. The unsupervised TKI interruption underscores that any consideration of treatment discontinuation should occur only under specialist supervision with close molecular monitoring, while the discordance between the observed response and reported L387M sensitivity patterns warrants further investigation.

PMID 42924531
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PubMedAnalytical chemistry2026-10-23

Hydrodynamic Cell Capture and Release Microfluidic Chip for Cancer Drug Screening.

Wang Xuefeng X, Li Wei W, Zhang Xiaoling X, Yang Jun J et al.

Microfluidic chip-based drug screening has attracted increasing attention owing to its miniaturization, automation, high throughput, simple operation, and excellent biocompatibility. Efficient release of target cells after co-culture with different drug concentrations is critical for investigating drug-induced alterations in cellular gene expression and enhancing microfluidic screening performance. In this study, a direction-sensitive microstructure with adaptive flow resistance regulation was constructed based on a fluidic-circuit-equivalent resistance model. This structure generated distinct distributions under forward and reverse flow directions, achieving efficient cell capture and release. Guided by theoretical analysis and simulation optimization, a microfluidic device integrating a concentration gradient generator, trap array, and flow resistance-regulating microchannels was fabricated. By simply switching the driving direction, the device can conveniently switch between forward capture and reverse release modes with high stability. In forward capture mode, the main channel exhibits the lowest flow resistance, and cells flow along the main channel and are captured in the traps. In reverse release mode, the main channel switches to the highest flow resistance, and cells in the traps are efficiently released backward along bypass channels to the collection outlet without recapture. Using K562 cells, the effects of channel width on cell capture and release efficiencies were investigated to determine the optimal design parameters. Finally, the device achieved a capture efficiency of 92.0 ± 4.4% and a release efficiency of 70.0 ± 8.6%, with maximum values of 97.2% and 87.8%, respectively. To further verify the device's applicability for drug screening, four concentrations of nilotinib were generated using the device. After K562 cells were cultured under the four concentrations for 48 h, the on-chip IC50 of nilotinib against K562 cells was determined to be approximately 10.79 μM, close to the result of 14.10 μM measured in the off-chip microplate. Subsequently, the treated cells were collected after reverse release and subjected to RNA-seq. The results showed that 20 μM nilotinib treatment significantly downregulated the expression of MYC, LYN, and BCL2L12, which are related to BCR-ABL signaling, by 18.3-fold, 3.6-fold, and 4.7-fold, respectively. Meanwhile, the treatment inhibited the viability of K562 cells to 23.9 ± 3.5%.

PMID 42915689
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PubMedEcotoxicology and environmental safety2026-10-23

Chronic exposure to the tire-wear contaminant 6-PPDQ induces senescence-associated biomarkers and neurobehavioral deficits: Involvement of ABL1-p53-autophagy signaling.

Ma Zejiang Z, Bai Manxue M, Xia Chunmei C, Li Jianguang J et al.

While 6-PPD quinone (6-PPDQ) is known for its acute lethality to salmonids, its chronic impacts on non-target species remain elusive. Here, we evaluated the chronic toxicity of 6-PPDQ across multiple biological models. Our results demonstrate that 6-PPDQ exposure significantly curtailed the survival and physiological motility of the nematode Caenorhabditis elegans, while inducing cellular senescence-associated biomarkers and a secretory phenotype (SASP) in human MRC-5 cells. In adult zebrafish, chronic exposure over a 28-month follow-up window precipitated cognitive and neurobehavioral deficits, characterized by impaired spatial learning, elevated agonistic reactivity, and glutamatergic excitotoxicity. Through computational screening, molecular docking, and pharmacological rescue, we identified ABL1 as a prioritized candidate target and functional mediator of 6-PPDQ toxicity. Total ABL1 protein abundance was elevated in exposed zebrafish brains alongside p53 accumulation and autophagic substrate (p62 and LC3-II) retention. Importantly, concurrent treatment with the ABL1 kinase inhibitor nilotinib attenuated p53 induction, restored autophagic flux, and rescued locomotor deficits, implicating the ABL1-associated pathway in these phenotypes. Because overt organismal morbidity was manifest predominantly at upper-bound exposure concentrations (10 µg/L), these phenotypes reflect chronic toxic stress rather than an acceleration of natural aging. These findings identify an ABL1-associated mechanism of chronic neurotoxicity and emphasize the need to assess long-term neurological risks associated with tire-wear pollution.

PMID 42913102
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PubMedCase reports in oncology2026-10-15

Synchronous Chronic Myeloid Leukemia and Metastatic Papillary Thyroid Carcinoma: A Case Report of a Diagnostic and Therapeutic Challenge.

Ishti Nada SalahAldin NSA, Alkhateeb Nagham N NN, Alhashlamon Khaled K, Hamadneh Shoroq S et al.

The synchronous presentation of chronic myeloid leukemia (CML) and papillary thyroid carcinoma (PTC) is rare and may create important diagnostic and therapeutic challenges. A 36-year-old woman presented with leukocytosis and was diagnosed with chronic-phase CML. During the initial workup, ^18F-FDG PET/CT showed diffuse marrow activity together with mild-to-moderate uptake in selected cervical and right paratracheal lymph nodes. Neck imaging demonstrated a nodular thyroid gland and cervical lymphadenopathy with suspicious features including cystic change and calcifications, raising concern for a synchronous second primary malignancy. Fine-needle aspiration confirmed PTC, and nodal sampling established metastatic PTC. Hematologic stabilization with nilotinib was initiated before surgery. The patient subsequently underwent total thyroidectomy with bilateral neck dissection. Histopathology revealed multifocal PTC with lymphatic invasion, extensive nodal metastases (59/67 lymph nodes positive), and extranodal extension. Final staging was pT2N1bM0, corresponding to AJCC 8th edition stage I. This case highlights the importance of careful evaluation of atypical imaging findings in patients with newly diagnosed CML and the critical role of tissue confirmation in distinguishing leukemic disease from a synchronous second primary malignancy. It also illustrates the complexity of treatment sequencing and the importance of multidisciplinary management in patients with dual primary cancers.

PMID 42877460
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