axl bemcentinib  (MedChemExpress)

Journal: bioRxiv

Article Title: AXL governs axolotl cardiac regeneration and directs mammalian cardiomyocyte dedifferentiation

doi: 10.64898/2025.12.21.695613

Figure Lengend Snippet: a , Representative images of P1 neonatal CMs 5 days after AAV9-AXL or AAV9-GFP infection stained for AXL or GFP (magenta), linage labeling of CMs (green), α-actinin (gray) and dapi. b , Representative images same as ( a ) only with addition of 0uM, 0.1uM or 1uM R428 (axl inhibitor). c , Quantification of sarcomere integrity from a,b. d-h , in-vivo AAV9-AXL/GFP administration at neonatal P1 and analyzed at 8 weeks. Representative image of AXL induced sarcomere disassembly ( d ) as evident by less α-actinin staining as calculated by automated sarcomere detection per area (average between samples in e , all cells combined in f ) and lower mean α-actinin mean pixel intensity (average between samples in g , all cells combined in h ). n=504 AXL-cells and 709 AXL+ cells. i, Representative images and quantification of EdU cell cycle indicators of P1 CMs in-vitro, 3 days after addition of AAV9-AXL or AAV9-GFP. j , Volcano plot generated from bulk-RNA seq of 6xAAV9-AXL and 4xAAV9-GFP samples, of P1 CMs in-vitro , 3 days after infection. Genes in red are significantly up or downregulated (1.5 > log2FC, -1.5 < log2FC, -log10P < 1xe-20), as calculated by DESeq2. Gene in blue are significant but not sufficiently changed. Genes in green are sufficiently up or down regulated but not significantly. k , Heatmap of known border zone or remote zone markers in AAV9-AXL (AXL) or AAV9-GFP (GFP) taken from bulk RNA-seq. Asterisk next to gene name shows p<0.05 using DESeq2 statistical test. m , Heatmap of known glycolytic enzymes in AAV9-AXL (AXL) or AAV9-GFP (GFP) taken from bulk RNA-seq. Asterisk next to gene name shows p<0.05 using DESeq2 statistical test. m , Ratio of Extracellular acidification rate (ECAR)/ Oxygen consumption rate (OCR) indicating the preference of pyruvate fate of either fermentation or oxidation by mitochondria. Glycolysis induction was calculated by subtraction of values after 2-Deoxy-D-glucose induction from glucose induction values. n , Heatmap of major ion channels selected from expression levels of adult mouse hearts in AAV9-AXL (AXL) or AAV9-GFP (GFP) taken from bulk RNA-seq. Asterisk next to gene name shows p<0.05 using DESeq2 statistical test. o , Myh6/Myh7 gene expression ratio as calculated from bulk RNA-seq normalized counts. p , Myl2/Myl7 gene expression ratio as calculated from bulk RNA-seq normalized counts. In all relevant panels * P < 0.05, ** P < 0.01, *** P < 0.001 ****P<0.0001 (statistical test: Mann-Whitney two-tailed T-test). In panels k,l and n, asterisk shows significant change as calculated by DESeq2.

Article Snippet: In experiments involving administration of AXL inhibitor (R428; HY-15150, MedChemExpress), the cells were treated with the inhibitor or DMSO 24 hours after AAV administration and fixed by day 5 post infection with one media refreshment.

Techniques: Infection, Staining, Labeling, In Vivo, In Vitro, Generated, RNA Sequencing, Expressing, Gene Expression, MANN-WHITNEY, Two Tailed Test

Journal: Advanced Science

Article Title: Inactivation of AXL in Cardiac Fibroblasts Alleviates Right Ventricular Remodeling in Pulmonary Hypertension

doi: 10.1002/advs.202508995

Figure Lengend Snippet: The impact of AXL expression on FB Function. A) The enrichment pathways of upregulated genes in Axl ‐positive FBs compared to Axl ‐negative FBs. BP, biological process; MF, molecular function. B–D) The GSEA analysis indicated enriched gene profiling related to cellular response to growth factor stimulus (B), cell migration (C), and ECM structural constituent (D) in Axl ‐positive FBs. E–G) The differences in growth score (E), migration score (F), and ECM score (G) between Axl ‐positive and Axl ‐negative FBs. H) The effect of Axl silencing on FB proliferation in response to hypoxia for 24 h, measured by EdU assay (distributed in four independent experiments). I) Correlation analysis reveals a significant positive relationship between Axl expression and collagen‐related genes in FBs. J–M) The effect of AXL inhibitor R428 on proliferation (J), migration (K, L), and synthesis of collagen COL1A1 (M) of FBs infected with AdAxl or AdCtrl in the presence or absence of R428 under hypoxic conditions (distributed in three independent experiments). Data represent mean ± SEM. ** P < 0.01, *** P < 0.001 compared to indicated group, as analyzed by One‐way ANOVA test.

Article Snippet: AXL inhibitor R428 (Cat# HY‐15150) and PI3K inhibitor LY294002 (Cat# HY‐10108) were purchased from MedChemExpress LLC.

Techniques: Expressing, Migration, EdU Assay, Infection

Journal: Advanced Science

Article Title: Inactivation of AXL in Cardiac Fibroblasts Alleviates Right Ventricular Remodeling in Pulmonary Hypertension

doi: 10.1002/advs.202508995

Figure Lengend Snippet: AXL‐exacerbated RV remodeling in PH is rescued by R428 or LY294002. A) Experimental scheme outlining the treatment protocol for mice that received either AAV9‐Postn‐hAXL or AAV9‐Postn‐Ctrl, followed by administration of LY294002 (a PI3K inhibitor) or R428 (an AXL inhibitor) every other day for two weeks, starting two weeks after HH exposure (G1‐G4 groups as indicated). B–D) RVSP (n = 5‐9/group) (B); RVFWT (n = 5‐9/group) (C) and TAPSE (n = 5‐9/group) (D) in mice receiving either AAV9‐Postn‐hAXL or AAV9‐Postn‐Ctrl, followed by administration of LY294002 or R428 under HH conditions. E, F) The transcriptional level of Nppa (E) and Nppb (F) in RV tissues from G1 to G4 groups (n = 5‐9/group). G, H) Representative HE staining images (G) and quantification analysis (H) revealed PI3K blockade or R428 mitigated RV hypertrophy fraction in AAV9‐Postn‐hAXL recipients exposed to HH conditions (n = 5–8/group). I, J) Representative WGA staining images (I) and quantification (J) demonstrated a reduced cardiomyocyte size in AAV9‐Postn‐hAXL recipients exposed to HH conditions (n = 5–8/group). K, L) Representative IHC staining images (K) and quantification (L) showed a reduction in Collagen I‐positive areas in RV tissue of mice receiving AAV9‐Postn‐hAXL under HH conditions (n = 5–8/group). M) Synopsis of proposed mechanism: In the context of PH, excessive AXL signaling activates the PI3K‐AKT pathway, facilitating the nuclear translocation of NFIC. This process promotes the transcription of targeted genes that enhance FB proliferation, migration, and collagen synthesis, contributing to RV remodeling. This remodeling can be mitigated by blocking the PI3K pathway with LY294002 and using R428 (Created in BioRender. Yan, Y. (2025) https://BioRender.com/s34e956). Data represent mean ± SEM. * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001 compared to indicated group, as analyzed by One‐way ANOVA test; Scale bar: 50 µm.

Article Snippet: AXL inhibitor R428 (Cat# HY‐15150) and PI3K inhibitor LY294002 (Cat# HY‐10108) were purchased from MedChemExpress LLC.

Techniques: Staining, Immunohistochemistry, Translocation Assay, Migration, Blocking Assay