Journal: Nature cancer

Article Title: Copper depletion inhibits electron transport chain activity and nucleotide synthesis to boost leukemia therapy

doi: 10.1038/s43018-026-01177-4

Figure Lengend Snippet: (a) Volcano plot of changing metabolites between SLC31A1-KO SEM cells and control cells. n = 3 biological replicates. (b) Aspartate and dihydroorotate (DHO) levels at baseline in SLC31A1-KO or control SEM cells with eGFP or SLC31A1 rescue. (c) Nucleotide levels in SLC31A1-KO SEM cells with eGFP or SLC31A1 rescue. (d) Volcano plot of changing metabolites between day 8 BCS-treated MOLT16 cells and control cells. n = 3 biological replicates. (e-f) Aspartate and (f) nucleotide levels in day 8 BCS-treated MOLT16 cells. (g-h) Volcano plot of significantly changing metabolites between day 14 BCS-treated (g) or SLC31A1-KO (h) SEM cells, with amino acids highlighted in pink. n = 3 biological replicates. (i) Western blot for DHODH levels in BCS-treated SEM (day 8), NALM6 (day 6) and MOLT16 cells (day 8); each lane represents an independent biological replicate. Actin is a loading control. . (j) Nucleotide levels in AOX-overexpressing SEM cells treated with BCS for 8 days. (k-l) Levels of aspartate, DHO, and IMP in (k) 14-day BCS-treated SEM cells overexpressing RFP or AOX, (l) or SLC31A1-KO SEM cells overexpressing RFP or AOX. DHO = dihydroorotate, CAA = carbamoyl aspartic acid, AOX = alternative oxidase, IMP = inosine monophosphate. Plotted data are mean ± SD. p-values from Šídák's multiple comparisons test.

Article Snippet: Immunoblotting was performed using the following primary antibodies: For reducing and denaturing western blot: vinculin (CST 13901; 1:2500) Beta actin (CST 8457; 1:2000) GAPDH (CST 2118L; 1:2000) MT-CO1/COX1 (abcam ab14705; 1:2000) COX4I1/COX4 (CST 4850; 1:1000) COX2 (Proteintech 55070–1-AP; 1:5000) DHODH (Santa Cruz E-8 sc-166348; 1:500) SDHA (CST 5839S; 1:1000) SLC31A1 (CST 13086S; 1:500) Beta tubulin (CST 2128P; 1:1000) Human Total OxPhos Cocktail (abcam ab110411; 1:1000) VDAC1/porin (abcam ab154856; 1:1000) Total ERK1/2 (CST 4696S; 1:1000) Phospho-ERK1/2 (CST 4370L; 1:1000) Primary antibodies were diluted in Signal Enhancer HIKARI Solution 1 (Nacalai USA NU00102).

Techniques: Control, Western Blot

Journal: In Silico Pharmacology

Article Title: Exploring Sm DHODH inhibition: natural products with potential anti-schistosomiasis activity

doi: 10.1007/s40203-026-00628-1

Figure Lengend Snippet: Overlay of the human DHODH enzyme and the S. mansoni enzyme to identify differences between the human (pink) and parasite (blue) structures. The protruding blue loop at the top of the structure corresponds to the potential site of Sm DHODH, which may coordinate the entry of compounds into the binding pocket. The presence of ten residues (Gly285 to Lys294) in the loop of binding site 2 (highly conserved across all species of the Schistosoma genus) allows for significant rearrangement in this region compared to other classes of DHODH structures

Article Snippet: Molecular dynamics analyses indicated that compound 3 induced significant conformational changes in the Sm DHODH structure, especially in the loop regions near the site 2, suggesting the enzyme’s structural flexibility upon binding with the ligand.

Techniques: Binding Assay

Journal: In Silico Pharmacology

Article Title: Exploring Sm DHODH inhibition: natural products with potential anti-schistosomiasis activity

doi: 10.1007/s40203-026-00628-1

Figure Lengend Snippet: a Three-dimensional representation of the Sm DHODH structure with emphasis on cluster 1. The regions in green correspond to the protein structure, while the orange areas represent the cavities identified from the analysis. Cluster 1 shows a connection between the active sites, suggesting potential interactions between these locations. b The yellow regions represent polar contacts of the binding sites, and the red regions indicate hydrophobic contacts.

Article Snippet: Molecular dynamics analyses indicated that compound 3 induced significant conformational changes in the Sm DHODH structure, especially in the loop regions near the site 2, suggesting the enzyme’s structural flexibility upon binding with the ligand.

Techniques: Binding Assay

Journal: In Silico Pharmacology

Article Title: Exploring Sm DHODH inhibition: natural products with potential anti-schistosomiasis activity

doi: 10.1007/s40203-026-00628-1

Figure Lengend Snippet: a Structure of the enzyme with the field of arrows, using mode 5, which show twisting or rotational movements between domains, domain bending, and global opening and closing movements; b representation of Sm DHODH in ball and stick model. Blue: regions with low B-factor values, meaning that the atoms in this area are more ordered or have lower mobility. Green and yellow: intermediate B-factor values. Red: regions with high B-factor values, suggesting more flexible or disordered atoms

Article Snippet: Molecular dynamics analyses indicated that compound 3 induced significant conformational changes in the Sm DHODH structure, especially in the loop regions near the site 2, suggesting the enzyme’s structural flexibility upon binding with the ligand.

Techniques:

Journal: In Silico Pharmacology

Article Title: Exploring Sm DHODH inhibition: natural products with potential anti-schistosomiasis activity

doi: 10.1007/s40203-026-00628-1

Figure Lengend Snippet: Results of the compounds docked at the biological receptor ( Sm DHODH) with the best poses obtained from the docking simulations at site 1, emphasizing hydrogen bonds with the residues in the selected site

Article Snippet: Molecular dynamics analyses indicated that compound 3 induced significant conformational changes in the Sm DHODH structure, especially in the loop regions near the site 2, suggesting the enzyme’s structural flexibility upon binding with the ligand.

Techniques:

Journal: In Silico Pharmacology

Article Title: Exploring Sm DHODH inhibition: natural products with potential anti-schistosomiasis activity

doi: 10.1007/s40203-026-00628-1

Figure Lengend Snippet: Results of the compounds 1–4 and PZQ docked to the biological receptor ( Sm DHODH) with the best poses obtained at the potential binding site. Hydrogen bonds with residues at site 2 are highlighted

Article Snippet: Molecular dynamics analyses indicated that compound 3 induced significant conformational changes in the Sm DHODH structure, especially in the loop regions near the site 2, suggesting the enzyme’s structural flexibility upon binding with the ligand.

Techniques: Binding Assay

Journal: In Silico Pharmacology

Article Title: Exploring Sm DHODH inhibition: natural products with potential anti-schistosomiasis activity

doi: 10.1007/s40203-026-00628-1

Figure Lengend Snippet: RMSD plots for the complexes formed between compound 3 and binding sites 1 ( a ) and 2 ( b ). The black lines represent the apo form of Sm DHODH, while the red lines correspond to the complexes formed with compound 3 at sites 1 ( a ) and 2 ( b )

Article Snippet: Molecular dynamics analyses indicated that compound 3 induced significant conformational changes in the Sm DHODH structure, especially in the loop regions near the site 2, suggesting the enzyme’s structural flexibility upon binding with the ligand.

Techniques: Binding Assay

Journal: In Silico Pharmacology

Article Title: Exploring Sm DHODH inhibition: natural products with potential anti-schistosomiasis activity

doi: 10.1007/s40203-026-00628-1

Figure Lengend Snippet: RMSF plots for the most stable structures of compound 3 at the binding sites 1 ( A ) and 2 ( B ) of the Sm DHODH enzyme

Article Snippet: Molecular dynamics analyses indicated that compound 3 induced significant conformational changes in the Sm DHODH structure, especially in the loop regions near the site 2, suggesting the enzyme’s structural flexibility upon binding with the ligand.

Techniques: Binding Assay

Journal: In Silico Pharmacology

Article Title: Exploring Sm DHODH inhibition: natural products with potential anti-schistosomiasis activity

doi: 10.1007/s40203-026-00628-1

Figure Lengend Snippet: Inhibition curves of Sm DHODH for compound 3 after incubation (0 and 2 h). The enzyme was incubated with different concentrations of compound 3, and the residual activity was measured

Article Snippet: Molecular dynamics analyses indicated that compound 3 induced significant conformational changes in the Sm DHODH structure, especially in the loop regions near the site 2, suggesting the enzyme’s structural flexibility upon binding with the ligand.

Techniques: Inhibition, Incubation, Activity Assay

Journal: In Silico Pharmacology

Article Title: Exploring Sm DHODH inhibition: natural products with potential anti-schistosomiasis activity

doi: 10.1007/s40203-026-00628-1

Figure Lengend Snippet: Molecular docking results of derivatives 3a, 3b, 3c, and 3d, highlighting hydrogen-bonding interactions with key residues (His50,Ser53, Tyr31, and Arg130) at site 1 of Sm DHODH

Article Snippet: Molecular dynamics analyses indicated that compound 3 induced significant conformational changes in the Sm DHODH structure, especially in the loop regions near the site 2, suggesting the enzyme’s structural flexibility upon binding with the ligand.

Techniques: