Journal: Cell Death Discovery

Article Title: AXL tyrosine kinase inhibitor TP-0903 induces ROS trigger neuroblastoma cell apoptosis via targeting the miR-335-3p/DKK1 expression

doi: 10.1038/s41420-025-02681-9

Figure Lengend Snippet: A Structure of TP-0903. B – D Normal proximal tubular HK-2 and NB SH-SY5Y and Neuro-2a cells were treated with TP-0903 at serial concentrations for 24 h, and then the cell growth was determined using MTT assay. Cell growth was presented as percentage of control (0 μM, 100%). E Apoptosis assay using Annexin V/PI staining and flow cytometric analysis, ( F ) mitochondrial membrane potential (MMP) analysis, or ( G ) Western blot for apoptotic signaling cascade. Quantitative analysis of apoptotic cells or loss of MMP cells was presented as a percentage of total cells. Protein levels were semi-quantitated by densitometric analysis. GAPDH was used as internal control. * and ** P < 0.05 and P < 0.01 as compared to control.

Article Snippet: TP-0903 (HY-12963) was purchased from MedChemExpress.

Techniques: MTT Assay, Control, Apoptosis Assay, Staining, Membrane, Western Blot

Journal: Cell Death Discovery

Article Title: AXL tyrosine kinase inhibitor TP-0903 induces ROS trigger neuroblastoma cell apoptosis via targeting the miR-335-3p/DKK1 expression

doi: 10.1038/s41420-025-02681-9

Figure Lengend Snippet: Cells were treated with 100 nM TP-0903 for 24 h, and then subjected to total RNA extraction and gene expression analysis by RNA-seq analysis. A The heatmap of differentially expressed genes (DEGs) with -2≤ log 2 FC ≤ 2 in response to TP-0903 treatment. B The top 10 biological processes affected by the DEGs using Gene ontology analysis. P -values < 0.05 were indicated as red color. Cells were treated with 100 nM TP-0903 for 24 h, and then subjected to assessment of ( C ) protein levels or ( D ) mRNA expression levels by Western blotting or qRT-PCR analysis, respectively. E Protein levels and ( F ) mRNA expression levels of DKK1 among HK2 (Normal), Neuro-2a, and SH-SY5Y cells using Western blot and qRT-PCR, respectively. ** P < 0.01 as compared to control. G Violin plots of DKK1 gene expression in paired normal (green) and NB tumor (red) gene array data from the TNMplot database.

Article Snippet: TP-0903 (HY-12963) was purchased from MedChemExpress.

Techniques: RNA Extraction, Gene Expression, RNA Sequencing, Expressing, Western Blot, Quantitative RT-PCR, Control

Journal: Cell Death Discovery

Article Title: AXL tyrosine kinase inhibitor TP-0903 induces ROS trigger neuroblastoma cell apoptosis via targeting the miR-335-3p/DKK1 expression

doi: 10.1038/s41420-025-02681-9

Figure Lengend Snippet: Cells were transfected with siRNA against DKK1 (si-DKK1), treated with 50 nM TP-0903 for 24 h, and subjected to ( A ) immunodetection of cleaved PARP (C-PARP), cleaved caspase-3 (C-Caspase-3), and DKK1; ( B ) cell viability assay; or ( C ) cell apoptosis assay using Annexin V/PI staining and flow cytometric analysis. ** P < 0.01 as compared to control (si-NC, 0 nM). # P < 0.05 as compared to TP-0903 alone (50 nM). D Binding mode for docked ligand TP-0903 (cyan) was shown as stick representation in DKK1 (left panel). Structural domains of DKK1 and the amino acid residues interaction with TP-0903 were indicated. Binding affinity between TP-0903 and DKK1 was −6.0 kcal/mol.

Article Snippet: TP-0903 (HY-12963) was purchased from MedChemExpress.

Techniques: Transfection, Immunodetection, Viability Assay, Apoptosis Assay, Staining, Control, Binding Assay

Journal: Cell Death Discovery

Article Title: AXL tyrosine kinase inhibitor TP-0903 induces ROS trigger neuroblastoma cell apoptosis via targeting the miR-335-3p/DKK1 expression

doi: 10.1038/s41420-025-02681-9

Figure Lengend Snippet: A Predicted binding site of miR-335-3p on 3’UTR of DKK1 gene. B Cells were treated with serial concentrations of TP-0903 for 24 h and subjected to assess miR-335-3p expression level by qRT-PCR. Neuro-2a cells were transfected with control-mimic or miR-335-mimic, treated with TP-0903, and subjected to ( C ) immunodetection of DKK1 and cleaved PARP (C-PARP) using Western blot analysis, ( D ) cell viability assay, ( E ) qRT-PCR to determine miR-335-3p expression level, ( F ) quantitation of signals on Western blots, or ( G ) cell apoptosis assay using Annexin V/PI staining and flow cytometric analysis. ** P < 0.01 as compared to control. # P < 0.05 as compared to TP-0903 alone (50 nM).

Article Snippet: TP-0903 (HY-12963) was purchased from MedChemExpress.

Techniques: Binding Assay, Expressing, Quantitative RT-PCR, Transfection, Control, Immunodetection, Western Blot, Viability Assay, Quantitation Assay, Apoptosis Assay, Staining

Journal: Cell Death Discovery

Article Title: AXL tyrosine kinase inhibitor TP-0903 induces ROS trigger neuroblastoma cell apoptosis via targeting the miR-335-3p/DKK1 expression

doi: 10.1038/s41420-025-02681-9

Figure Lengend Snippet: A Cells were treated with TP-0903 for 24 h and subjected to ROS assay. Cells were treated with 50 nM TP-0903 or TP-0903 combined with NAC for 24 h and subjected to ( B ) ROS assay, ( C ) apoptosis assay using Annexin V/PI staining and flow cytometric analysis, ( D ) immunodetection of C-PARP and DKK1 by Western blot, or ( E ) qRT-PCR to determine miR-335-3p expression level. GAPDH was used as internal control. Signals were semi-quantitated by densitometric analysis. ** P < 0.01 as compared to control. # P < 0.05 as compared to TP-0903 alone (50 nM). Scale bar=20 μm.

Article Snippet: TP-0903 (HY-12963) was purchased from MedChemExpress.

Techniques: ROS Assay, Apoptosis Assay, Staining, Immunodetection, Western Blot, Quantitative RT-PCR, Expressing, Control

Journal: Cell Death Discovery

Article Title: AXL tyrosine kinase inhibitor TP-0903 induces ROS trigger neuroblastoma cell apoptosis via targeting the miR-335-3p/DKK1 expression

doi: 10.1038/s41420-025-02681-9

Figure Lengend Snippet: Balb/c nude mice were inoculated with Neuro-2a cells, and then oral administration of PBS or TP-0903 (10 mg/kg) every 3 days for 20 days. A Representative tumors and ( C ) tumor weights in xenografted mice. Changes in ( B ) tumor volume and ( D ) mouse body weights during the 20-day treatment period. Tumors were acquired and subjected to ( E ) Western blot or ( F ) qRT-PCR to assess DKK1 protein and mRNA expression level, respectively. G IHC assay to assess cell proliferation and DKK1 expression in tumor tissues. H H&E staining to assess tissue morphology. * and **, P < 0.05 and P < 0.01 as compared to control group.

Article Snippet: TP-0903 (HY-12963) was purchased from MedChemExpress.

Techniques: Western Blot, Quantitative RT-PCR, Expressing, Staining, Control

Journal: Cell Death Discovery

Article Title: AXL tyrosine kinase inhibitor TP-0903 induces ROS trigger neuroblastoma cell apoptosis via targeting the miR-335-3p/DKK1 expression

doi: 10.1038/s41420-025-02681-9

Figure Lengend Snippet: TP-0903 promotes ROS generation, upregulates miR-335-3p expression, consequently downregulating DKK1 expression and leading to cell apoptosis.

Article Snippet: TP-0903 (HY-12963) was purchased from MedChemExpress.

Techniques: Expressing

Journal: Experimental Hematology & Oncology

Article Title: AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies

doi: 10.1186/s40164-024-00566-8

Figure Lengend Snippet: Overview of type I AXL inhibitors and their current status in clinical trials for AML

Article Snippet: TP-0903 (Dubermatinib) , Tolero Pharmaceuticals , AXL, FLT3 , 27 nM (in vitro) , NCT03013998 , Ib/II , AML , Biomarker-based multidrug therapy , Recruiting.

Techniques: Clinical Proteomics, In Vitro, Biomarker Discovery, Mutagenesis