Journal: Molecular Medicine Reports

Article Title: AZD1080, a specific inhibitor of GSK-3β, inhibits stemness and malignancies in osteosarcoma cancer stem-like cells

doi: 10.3892/mmr.2025.13613

Figure Lengend Snippet: AZD1080 presented no obvious effect on proliferation or apoptosis in CSCs derived from U2OS and 143B. (A) Following culture in SFM for 5 and 10 days, cell morphology was observed. (B) After 5 days of culture in SFM, cells were collected and total protein was employed for western blot analysis for OCT4 and SOX2. *P<0.05, vs. PCs group. After 1, 2 or 3 days of co-culture with 10 µmol/l AZD1080, cell viability was detected by performing (C) CCK-8 assay, (D) cell cycle distribution was detected by flow cytometry assay following PI staining and (E) cell apoptosis was detected by performing flow cytometry assay following FITC/PI double staining. CSCs, cancer stem cells; PCs, parental cells; SFM, serum-free culture medium.

Article Snippet: AZD1080 is an effective and selective small molecule inhibitor of GSK3, first reported to be synthesized by AstraZeneca in 2013 ( , ).

Techniques: Derivative Assay, Western Blot, Co-Culture Assay, CCK-8 Assay, Flow Cytometry, Staining, Double Staining

Journal: Molecular Medicine Reports

Article Title: AZD1080, a specific inhibitor of GSK-3β, inhibits stemness and malignancies in osteosarcoma cancer stem-like cells

doi: 10.3892/mmr.2025.13613

Figure Lengend Snippet: Addition of AZD1080 promoted dissociation of spheres and cell attachment. (A) 100 Spheres >50 µm in diameter were co-cultured with or without 10 µmol/l AZD1080 for 1–3 days in SFM and sphere morphology and attachment capacity were observed. (B) Total protein of CSCs co-cultured with or without 10 µmol/l AZD1080 for 1, 2 or 3 days was collected and analyzed by western blotting to detect OCT4 and SOX2. *P<0.05, vs. mock group. CSCs, cancer stem cells.

Article Snippet: AZD1080 is an effective and selective small molecule inhibitor of GSK3, first reported to be synthesized by AstraZeneca in 2013 ( , ).

Techniques: Cell Attachment Assay, Cell Culture, Western Blot

Journal: Molecular Medicine Reports

Article Title: AZD1080, a specific inhibitor of GSK-3β, inhibits stemness and malignancies in osteosarcoma cancer stem-like cells

doi: 10.3892/mmr.2025.13613

Figure Lengend Snippet: Addition of AZD1080 inhibited sphere formation without affecting cell attachment. (A) AZD1080 (10 µmol/l) was added in SFM for U2OS and 143B culture for 1–4 days and cell morphology and sphere formation were imaged. (B) Total protein of cells co-cultured with or without 10 µmol/l AZD1080 for 1 and 4 days was collected and analyzed by western blotting to detect OCT4 and SOX2. *P<0.05, vs. mock group. SFM, serum-free culture medium.

Article Snippet: AZD1080 is an effective and selective small molecule inhibitor of GSK3, first reported to be synthesized by AstraZeneca in 2013 ( , ).

Techniques: Cell Attachment Assay, Cell Culture, Western Blot

Journal: Molecular Medicine Reports

Article Title: AZD1080, a specific inhibitor of GSK-3β, inhibits stemness and malignancies in osteosarcoma cancer stem-like cells

doi: 10.3892/mmr.2025.13613

Figure Lengend Snippet: Addition of AZD1080 inhibited invasion and tumor formation in soft agar of CSCs derived from U2OS and 143B. Spheres were collected and dissociated to obtain single cells of CSCs, which were then co-cultured with 10 µmol/l AZD1080 for 24 h. (A) The invasion capacity of single cells of CSCs were detected by performing Transwell assay. (B) Tumor formation assay was measured in soft agar. **P<0.01, ***P<0.001, ****P<0.0001 vs. mock group. CSCs, cancer stem cells.

Article Snippet: AZD1080 is an effective and selective small molecule inhibitor of GSK3, first reported to be synthesized by AstraZeneca in 2013 ( , ).

Techniques: Derivative Assay, Cell Culture, Transwell Assay, Tube Formation Assay

Journal: Molecular Medicine Reports

Article Title: AZD1080, a specific inhibitor of GSK-3β, inhibits stemness and malignancies in osteosarcoma cancer stem-like cells

doi: 10.3892/mmr.2025.13613

Figure Lengend Snippet: AZD1080 inhibited GSK-3β phosphorylation and its downstream regulated signaling. Spheres were collected and dissociated to obtain single cells of CSCs, which were then co-cultured with 10 µmol/l AZD1080 for 24 h. Total protein was collected to detect GSK-3β total protein and phosphorylated protein, including its downstream regulated proteins, CYCLIND1, β-catenin, HEY1, HES1 in (A) U2OS CSCs and (B) 143B cells. *P<0.05 vs. mock group. GSK-3β, glycogen synthase kinase-3β; CSCs, cancer stem cells.

Article Snippet: AZD1080 is an effective and selective small molecule inhibitor of GSK3, first reported to be synthesized by AstraZeneca in 2013 ( , ).

Techniques: Phospho-proteomics, Cell Culture

Journal: Molecular Medicine Reports

Article Title: AZD1080, a specific inhibitor of GSK-3β, inhibits stemness and malignancies in osteosarcoma cancer stem-like cells

doi: 10.3892/mmr.2025.13613

Figure Lengend Snippet: AZD1080 inhibited PTEN signaling via regulating GSK-3β activity. (A) After AZD1080 treatment for 24 h, or GSK-3β knockdown for 48 h, total protein was collected from CSCs derived from U2OS and 143B and western blot was performed to detect GSK-3β, MMP2, MMP9 and PTEN. *P<0.05, vs. mock group; # P<0.05, vs. siNC group. (B) Following AZD1080 treatment or GSK-3β knockdown, mRNA levels including GSK-3β, MMP2, MMP9 were measured by performing reverse transcription-quantitative PCR. *P<0.05, vs. mock group; # P<0.05, vs. siNC group. PTEN, phosphatase with tensin homology; GSK-3β, glycogen synthase kinase-3β; si, small interfering; NC, negative control.

Article Snippet: AZD1080 is an effective and selective small molecule inhibitor of GSK3, first reported to be synthesized by AstraZeneca in 2013 ( , ).

Techniques: Activity Assay, Knockdown, Derivative Assay, Western Blot, Reverse Transcription, Real-time Polymerase Chain Reaction, Negative Control

Journal: Advanced Pharmaceutical Bulletin

Article Title: Role of GSK-3β Inhibitors: New Promises and Opportunities for Alzheimer’s Disease

doi: 10.34172/apb.2023.071

Figure Lengend Snippet: ATP competitive inhibitors of GSK-3β in Alzheimer’s disease

Article Snippet: AstraZeneca described ATP-competitive GSK3β inhibitors such AZD1080 as orally active & brain permeable GSK-3 inhibitors that inhibited human GSK-3β in the nanomolar range, however owing to nephrotoxicity in phase 1 clinical study targeting AD, further development of this inhibitor was terminated.

Techniques: Inhibition

Journal: Advanced Pharmaceutical Bulletin

Article Title: Role of GSK-3β Inhibitors: New Promises and Opportunities for Alzheimer’s Disease

doi: 10.34172/apb.2023.071

Figure Lengend Snippet: Preclinical studies involving GSK-3β inhibitors

Article Snippet: AZD1080 , Sprague–Dawley rats , Normal Rodent brain following in vivo administration of the acute dose of AZD1080 (1, 3, or 10 mol/kg) p.o. , Inhibition of tau phosphorylation and reduction of the phosphorylated to total Glycogen Synthase ratio , .

Techniques: Transgenic Assay, Inhibition, Marker, In Vivo, Phospho-proteomics, Mutagenesis