2800 fda approved drugs  (TargetMol)

Journal: Advanced Science

Article Title: Chemotherapy‐Activated GSK3β‐DNMT1 Signaling Upregulates CD47 to Evade Macrophage Phagocytosis and Drive Temozolomide Resistance in Glioblastoma

doi: 10.1002/advs.77471

Figure Lengend Snippet: WIN 51708 disrupts the p‐GSK3β‐Y216‐DNMT1‐S977 interface to restore DNMT1 stability and overcome TMZ resistance in GBM. (A) Schematic of virtual screening steps for small molecule compounds. This panel was generated with BioRender.com. (B) The rank list of Top3 target compounds for disrupts the P‐GSK3β‐Y216 and DNMT1 S977 interaction. (C) Molecular docking model (left) and chemical structure (right) of WIN 51708 showing predicted binding at the p‐GSK3β‐Y216‐DNMT1‐S977 interface. (D) Dose‐response curves and IC 50 determination for WIN 51708 in U87‐R and GL261‐R cells by CCK‐8 assay. (E) CCK‐8 assay measuring TMZ‐induced cytotoxicity in U87‐R (left) and GL261‐R (right) cells co‐treated with DMSO or WIN 51708 at sub‐IC 50 concentrations. ( n = 6, * p < 0.05, ** p < 0.01, unpaired t‐ test). (F) Western blot analysis of DNMT1 phosphorylation and ubiquitination in U87‐S cells treated with TMZ, WIN 51708 or Substance P (SP). (G) Western blot analysis of DNMT1 phosphorylation and ubiquitination in U87‐R cells treated with WIN 51708 or SP. (H) Representative image (left) and phagocytosis (right) of patient‐derived GBM organoids (PDOs) growth after combined treatment of WIN 51708 and TMZ. (Scale bars, 20 µm). (I) Growth curve of PDOs after combined treatment of WIN 51708 and TMZ. ( n = 6, ** p < 0.01, unpaired t‐ test). (J) Schematic of combined treatment of WIN 51708 (5 mg kg − 1 , intraperitoneal) and TMZ (20 mg kg − 1 , oral gavage) in GL261‐R mouse model. (K) In vivo bioluminescent imaging (left) and quantification (right) of tumor bearing mice after combined treatment of WIN 51708 and TMZ in mTMZ‐R models. ( n = 6, * p < 0.05, ** p < 0.01, one‐way ANOVA). (L) Flow cytometry‐based in vivo phagocytosis (left) and quantification (right) in panel K. ( n = 3, * p < 0.05, ** p < 0.01, ns = not significant, one‐way ANOVA).

Article Snippet: To identify small‐molecule inhibitors that potentially disrupt the interaction between p‐GSK3β‐Y216 and the S977 region of DNMT1, virtual screening was performed using a bioactive compound library from the TargetMol database ( https://www.targetmol.cn ), comprising 17,760 known bioactive compounds.

Techniques: Generated, Binding Assay, CCK-8 Assay, Western Blot, Phospho-proteomics, Ubiquitin Proteomics, Derivative Assay, In Vivo, Imaging, Flow Cytometry

Journal: Frontiers in Cellular and Infection Microbiology

Article Title: Niemann-Pick type C1 protein regulates epidermal growth factor receptor stability in hepatic cells and facilitates the early steps of Hepatitis B virus infection

doi: 10.3389/fcimb.2026.1905331

Figure Lengend Snippet: FDA-approved NPC1 inhibitors reduce HBV entry. (A) HepG2-hNTCP cells were treated with either itraconazole, posaconazole, verapamil, amiodarone at the indicated concentrations, or DMSO for 24 h prior to HBV inoculation (300 GEq/cell). Secreted HBeAg levels were quantified by ELISA at 7 dpi. (B) Drug toxicity was evaluated by MTS assay, after 24 h of incubation. Data are presented as mean ± SD percentages from DMSO controls from three (A) or two (B) independent experiments performed in at least two biological replicates. Statistical significance was determined by using one-way ANOVA (****p < 0.0001, ns, not significant).

Article Snippet: Cells were treated with U18666A (MedchemExpress, 3039-71-2) or various FDA-approved drugs (TargetMoi, L4200), at concentrations indicated in figure captions, for 24 h prior to HBV infection.

Techniques: Enzyme-linked Immunosorbent Assay, MTS Assay, Incubation