Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of a selective PI3Kα inhibitor via structure-based virtual screening for targeted colorectal cancer therapy

doi: 10.1080/14756366.2025.2468852

Figure Lengend Snippet: Validation of the docking protocol was performed through ligand extraction and redocking. The co-crystal ligand, alpelisib, originally identified in complex with the PI3Kα protein via X-ray crystallography, was extracted and re-docked into the protein’s binding site. The accuracy of this protocol was evaluated by calculating the RMSD between the superimposed poses of the ligand in the original crystal structure (cyan color) and its docked conformation (purple color).

Article Snippet: The screening protocol encompassed ∼3000 compounds sourced from the Protein Kinase Diversity Set and the Phosphatidylinositol 3-Kinase (PI3K) Targeted Library by Life Chemicals (accessed 15 May 2024).

Techniques: Extraction, Binding Assay

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of a selective PI3Kα inhibitor via structure-based virtual screening for targeted colorectal cancer therapy

doi: 10.1080/14756366.2025.2468852

Figure Lengend Snippet: Inhibitory effects of candidate compounds on PI3Kα and their selectivity profile across PI3K isoforms. The ADP-Glo™ assay was employed using purified PI3Kα to assess the kinase inhibition exerted by compounds F0608-0019 (A), F2490-0372 (B), and the reference inhibitor, alpelisib (C), across a range of concentrations. The percentage inhibition of PI3K isoforms β and γ was determined at a concentration of 10 µM (D) using the ADP-Glo™ kinase activity assay. The data represents the mean ± SEM of two biological replicates.

Article Snippet: The screening protocol encompassed ∼3000 compounds sourced from the Protein Kinase Diversity Set and the Phosphatidylinositol 3-Kinase (PI3K) Targeted Library by Life Chemicals (accessed 15 May 2024).

Techniques: Glo Assay, Purification, Inhibition, Concentration Assay, Kinase Assay

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of a selective PI3Kα inhibitor via structure-based virtual screening for targeted colorectal cancer therapy

doi: 10.1080/14756366.2025.2468852

Figure Lengend Snippet: Molecular dynamics simulation of alpelisib and F0608-0019 in complex with PI3Kα. RMSD analysis of the ligand-protein complexes, illustrating the stability of alpelisib (A) and F0608-0019 (D) bound to PI3Kα. RMSF analysis depicts the flexibility of amino acid residues in the PI3Kα complexed with alpelisib (B) and F0608-0019 (E). Hydrogen bond formation analysis indicates the interactions of alpelisib (C) and F0608-0019 (F) with PI3Kα.

Article Snippet: The screening protocol encompassed ∼3000 compounds sourced from the Protein Kinase Diversity Set and the Phosphatidylinositol 3-Kinase (PI3K) Targeted Library by Life Chemicals (accessed 15 May 2024).

Techniques:

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of a selective PI3Kα inhibitor via structure-based virtual screening for targeted colorectal cancer therapy

doi: 10.1080/14756366.2025.2468852

Figure Lengend Snippet: Two-dimensional ligand interaction map of PI3Kα inhibitor complexes extracted from the last frame of molecular dynamics simulations. This analysis provides a detailed view of the ligand-protein interactions, highlighting the binding poses of alpelisib (A) and F0608-0019 (B). Interaction bonds are represented as dashed lines connecting the relevant atoms. Distinct colours denote different types of interactions: green indicates conventional hydrogen bonds, light orange represents π-sulfur interactions, dark orange signifies π-anion interactions, and pink depicts π-alkyl interactions.

Article Snippet: The screening protocol encompassed ∼3000 compounds sourced from the Protein Kinase Diversity Set and the Phosphatidylinositol 3-Kinase (PI3K) Targeted Library by Life Chemicals (accessed 15 May 2024).

Techniques: Binding Assay

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Discovery of a selective PI3Kα inhibitor via structure-based virtual screening for targeted colorectal cancer therapy

doi: 10.1080/14756366.2025.2468852

Figure Lengend Snippet: Total energy contributions of key residues in the binding of PI3Kα inhibitors. Analysis of the energy contributions of essential residues involved in the binding interactions of PI3Kα with the inhibitors alpelisib (A) and F0608-0019 (B).

Article Snippet: The screening protocol encompassed ∼3000 compounds sourced from the Protein Kinase Diversity Set and the Phosphatidylinositol 3-Kinase (PI3K) Targeted Library by Life Chemicals (accessed 15 May 2024).

Techniques: Binding Assay

Journal: Aging (Albany NY)

Article Title: Geniposide-mediated protection against amyloid deposition and behavioral impairment correlates with downregulation of mTOR signaling and enhanced autophagy in a mouse model of Alzheimer's disease

doi: 10.18632/aging.101759

Figure Lengend Snippet: Geniposide treatment decreases mTOR activation markers in brains of APP/PS1 mice. Hippocampal expression of Akt, mTOR, and 4E-BP1, and their respective phosphorylated forms was detected by western blot. The expression of p-Akt ( A ) and p-mTOR ( B ) was enhanced in APP/PS1 mice compared to WT, and geniposide attenuated this increase. The expression of p-4E-BP1 ( C ) in APP/PS1 mice was reduced compared to WT, and geniposide partly restored this decrease. Data are presented as mean ± SEM (n = 6). *** p < 0.001, ** p < 0.01, * p < 0.05 vs. WT; # p < 0.05 vs. APP/PS1 mice (one-way ANOVA, Tukey's Multiple Comparison Test). WT: wild-type mice. GP: geniposide.

Article Snippet: The membranes were blocked in 5% bovine serum albumin in TBST (Tris-buffered saline with 0.05% Tween-20) for 1h, and incubated overnight at 4°C with primary antibodies directed against: Akt (1:1,000), p-Akt (1:2,000), mTOR (1:1,000), p-mTOR (1:1,000), 4E-BP1 (1:1,000), or p-4E-BP1 (1:2,000), followed by incubation at 4°C for 2h with a goat-anti-rabbit IgG-horseradish peroxidase-conjugated secondary antibody (Boster, Wuhan, China).

Techniques: Activation Assay, Expressing, Western Blot, Comparison