t2590 erismodegib sonidegib targetmol  (TargetMol)

Journal: The FASEB Journal

Article Title: HOXB4 Promotes Bladder Cancer Progression in Part Through Transcriptional Activation of Smoothened

doi: 10.1096/fj.202503614R

Figure Lengend Snippet: Vismodegib suppresses BCa xenograft growth. (A) Treatment schema: Mice bearing xenografts received vismodegib (100 mg/kg, oral gavage, once daily) from day 1 to 21; controls received 0.5% methylcellulose as vehicle. (B) Tumor growth curves under vismodegib versus vehicle. (C and D) Representative tumor images and terminal tumor weights on day 21. The results are shown as the mean ± standard deviation (SD). Tumor growth curve (B) was analyzed by two‐way repeated‐measures ANOVA. Multiple‐group comparisons (D) were analyzed using one‐way ANOVA. Statistical significance is indicated as follows: * p < 0.05, ** p < 0.01, *** p < 0.001.

Article Snippet: Vismodegib (HY‐10440) was obtained from MedChemExpress.

Techniques: Standard Deviation

Journal: Biomaterials Research

Article Title: Tryptamine-Functionalized Lipid Nanocarriers Co-delivering SMO/BRD4 Inhibitors for Synergistic Medulloblastoma Therapy

doi: 10.34133/bmr.0237

Figure Lengend Snippet: JQ1 and saikosaponin B1 (SSB1) synergistically inhibit GLI expression, arrest cells in the G 0 /G 1 phase, and promote the apoptosis of medulloblastoma (MB) cells. (A and B) The inhibition of GLI1/2 , PTCH1 , SHH , and MYCN messenger RNA (mRNA) expression in DAOY and D341 Med cells with JQ1 and SSB1 treatment for 48 h was determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). (C and D) Cell cycle of DAOY and D341 Med cells treated with JQ1, SSB1, and their combination for 48 h. (E and F) Cell apoptosis of DAOY and D341 Med cells treated with JQ1, SSB1, and their combination for 48 h. (G and H) CYCLIN D1 and BAX mRNA expression in DAOY and D341 Med cells after incubation with JQ1 and SSB1 combination (* P < 0.05; ** P < 0.01).

Article Snippet: SSB1, GDC-0449, and JQ1 were procured from MedChemExpress (Princeton, USA).

Techniques: Expressing, Inhibition, Reverse Transcription, Polymerase Chain Reaction, Quantitative RT-PCR, Incubation

Journal: Biomaterials Research

Article Title: Tryptamine-Functionalized Lipid Nanocarriers Co-delivering SMO/BRD4 Inhibitors for Synergistic Medulloblastoma Therapy

doi: 10.34133/bmr.0237

Figure Lengend Snippet: JQ1 and SSB1 synergistically down-regulate MB stem cell markers and reduce frequency. (A and B) mRNA levels of stem cell markers in CD15 + MB and CD15 − MB cells. (C and D) The mRNA levels of stem cell markers in CD15 + DAOY and CD15 + ONS-76 cells after incubation with JQ1 and SSB1 for 48 h were determined by real-time RT-PCR. (E and F) CD15 + MB stem cell frequency reduced after incubation with JQ1, SSB1, and their combination. (G and H) CD133 expression on CD15 + MB stem cells after incubation with JQ1, SSB1, and their combination (* P < 0.05; ** P < 0.01).

Article Snippet: SSB1, GDC-0449, and JQ1 were procured from MedChemExpress (Princeton, USA).

Techniques: Incubation, Quantitative RT-PCR, Expressing

Journal: Biomaterials Research

Article Title: Tryptamine-Functionalized Lipid Nanocarriers Co-delivering SMO/BRD4 Inhibitors for Synergistic Medulloblastoma Therapy

doi: 10.34133/bmr.0237

Figure Lengend Snippet: JQ1 and SSB1 synergistically increase MB stem cell apoptosis. (A and B) JQ1 and SSB1 inhibit CD15 + MB stem cell viability in a dose-dependent manner. (C and D) mRNA expression of senescent markers in CD15 + MB stem cells with JQ1 and SSB1 incubation for 48 h. (E and F) The apoptosis of CD15 + MB stem cells after incubation with JQ1, SSB1, and their combination, as well as the representative flow cytometry scatter plots. PI, propidium iodide; FITC, fluorescein isothiocyanate.

Article Snippet: SSB1, GDC-0449, and JQ1 were procured from MedChemExpress (Princeton, USA).

Techniques: Expressing, Incubation, Flow Cytometry

Journal: Biomaterials Research

Article Title: Tryptamine-Functionalized Lipid Nanocarriers Co-delivering SMO/BRD4 Inhibitors for Synergistic Medulloblastoma Therapy

doi: 10.34133/bmr.0237

Figure Lengend Snippet: JQ1 and SSB1 synergistically down-regulate MMP2 and inhibit MB metastasis. (A and B) JQ1 and SSB1 down-regulate MMP2 mRNA expression in MB cells. (C and D) The microscope images and quantitative analysis of DAOY and D341 Med cells after incubation with JQ1, SSB1, and their combination. The microscope images and quantitative analysis of MB cell migration (E and F) and invasion (G and H) after incubation with JQ1, SSB1, and their combination (* P < 0.05; ** P < 0.01). GSH, glutathione; DAPI, 4′,6-diamidino-2-phenylindole; OCT2, organic cation transporter 2.

Article Snippet: SSB1, GDC-0449, and JQ1 were procured from MedChemExpress (Princeton, USA).

Techniques: Expressing, Microscopy, Incubation, Migration

Journal: Biomaterials Research

Article Title: Tryptamine-Functionalized Lipid Nanocarriers Co-delivering SMO/BRD4 Inhibitors for Synergistic Medulloblastoma Therapy

doi: 10.34133/bmr.0237

Figure Lengend Snippet: Characterization of drug-loaded nanoparticles (NPs). (A) Dynamic light scattering (DLS) of JQ1- and SSB1-loaded nontargeted NPs and tryptamine (Try)-derived NPs. (B) NP morphology analyzed by transmission electron microscopy (TEM). (C) The cumulative release profiles of JQ1 and SSB1 in nontargeted NPs and Try-derived NPs at pH 7.4 and 6.8. (D) Stability of JQ1- and SSB1-loaded nano-targeted NPs and Try-derived NPs at room temperature for 72 h. (E and F) Cell viability of MB cells after 48-h incubation with JQ1- and SSB1-loaded nontargeted NPs and Try-derived NPs. (G) Scheme of the in vitro transwell blood–brain barrier (BBB) model. (H and I) The cellular uptake of Cy5.5-decorated nontargeted NPs and Try-derived NPs in human brain microvascular endothelial cells (HBMECs) and MB cells after 4-h incubation was analyzed using flow cytometry. (J) The cellular uptake of Cy5.5-decorated nontargeted NPs and Try-derived NPs in DAOY cells was observed by confocal microscopy.

Article Snippet: SSB1, GDC-0449, and JQ1 were procured from MedChemExpress (Princeton, USA).

Techniques: Derivative Assay, Transmission Assay, Electron Microscopy, Incubation, In Vitro, Flow Cytometry, Confocal Microscopy

Journal: Biomaterials Research

Article Title: Tryptamine-Functionalized Lipid Nanocarriers Co-delivering SMO/BRD4 Inhibitors for Synergistic Medulloblastoma Therapy

doi: 10.34133/bmr.0237

Figure Lengend Snippet: Try-derived NPs significantly enhance BBB permeability and drug biodistribution after systemic administration. (A and B) Try-derived NPs conjugated with Cy5.5 significantly increase brain permeability compared to nontargeted NPs in healthy NSG mice analyzed using the IVIS system and confocal microscopy. (C) Try-decorated NPs conjugated with Cy5.5 significantly increase MB tumor cellular uptake compared to nontargeted NPs in MB-bearing NSG mice. (D) JQ1 and SSB1 concentrations in the brains of orthotopic MB tumor-bearing NSG mice at 6 and 24 h post-systemic administration of drug-loaded Try-derived NPs or nontargeted NPs at a dose of 10 mg/kg (* P < 0.05; ** P < 0.01). GFP, green fluorescent protein.

Article Snippet: SSB1, GDC-0449, and JQ1 were procured from MedChemExpress (Princeton, USA).

Techniques: Derivative Assay, Permeability, Confocal Microscopy

Journal: Biomaterials Research

Article Title: Tryptamine-Functionalized Lipid Nanocarriers Co-delivering SMO/BRD4 Inhibitors for Synergistic Medulloblastoma Therapy

doi: 10.34133/bmr.0237

Figure Lengend Snippet: Anti-tumor efficacy of targeted NPs loaded with JQ1 and SSB1 after systemic administration into orthotopic MB-bearing NSG mice. (A) Bioluminescence images and (B) quantitative analysis of IVIS signal intensity (photons/s/cm 2 /sr) of MB tumors at different times. (C) Average mouse body weight changes during treatment. (D) Representative microscopic pictures of hematoxylin and eosin (H&E) and immunohistochemical staining of MB tissues for OCT4, MMP2, KI67, and CLEAVED CASPASE 3. Scale bar 100 μm, inset image ×20.

Article Snippet: SSB1, GDC-0449, and JQ1 were procured from MedChemExpress (Princeton, USA).

Techniques: Immunohistochemical staining, Staining