molecule library  (TargetMol)

Journal: Nature Communications

Article Title: Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR

doi: 10.1038/s41467-026-76518-z

Figure Lengend Snippet: A Chemical structures of small molecule ligands of C3aR, SB290157 and JR14a, drawn using ChemDraw software. B SB290157/JR14a-induced G-protein-coupling measured using NanoBiT-based G-protein dissociation and GloSensor-based cAMP assays upon stimulation of HEK-293 cells expressing the indicated receptors. Data was normalized with respect to the response at the lowest ligand concentration treated as 100% (mean ± SEM; n = 3 independent experiments). C SB290157/JR14a-induced βarr1/2 recruitment measured using a NanoBiT-based assay upon stimulation of HEK-293 cells expressing the indicated receptors. Data was normalized to the response at the lowest ligand concentration, which was set to 1 (mean ± SEM; n = 3 independent experiments). Comparison of Emax and EC 50 values of the corresponding data are presented in Supplementary Table . Source data are provided as a file.

Article Snippet: Small-molecule compounds SB290157 and JR14a were obtained from MedChem Express (Cat. No: HY-101502A for SB290157; Cat. No: HY-138161 for JR14a).

Techniques: Software, Expressing, Concentration Assay, Comparison

Journal: Nature Communications

Article Title: Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR

doi: 10.1038/s41467-026-76518-z

Figure Lengend Snippet: A–K Structural comparison of the indicated structures, highlighting the key differences in the overall positioning of various ligands in the orthosteric pocket of the human and mouse C3aR. PDB: 8I9L for hC3a-hC3aR, 9KZK for mC3a-mC3aR, 9KV8 for hTLQP-21-mC3aR, 9KV6 for mTLQP-21-mC3aR, 8I95 for EP54-hC3aR, 9UMJ for EP54-mC3aR, 9KUT for JR14a-hC3aR, 9L0H for JR14a-mC3aR and 9KVP for SB290157-hC3aR complex.

Article Snippet: Small-molecule compounds SB290157 and JR14a were obtained from MedChem Express (Cat. No: HY-101502A for SB290157; Cat. No: HY-138161 for JR14a).

Techniques: Comparison

Journal: Nature Communications

Article Title: Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR

doi: 10.1038/s41467-026-76518-z

Figure Lengend Snippet: Selected interactions of the indicated ligands in the orthosteric pocket of the human and mouse C3aR, highlighting the conserved interactions with those of C3a. PDB: 8I9L for hC3a-hC3aR, 9KZK for mC3a-mC3aR, 9KV8 for hTLQP-21-mC3aR, 9KV6 for mTLQP-21-mC3aR, 8I95 for EP54-hC3aR, 9UMJ for EP54-mC3aR, 9KUT for JR14a-hC3aR, 9L0H for JR14a-mC3aR and 9KVP for SB290157-hC3aR complex.

Article Snippet: Small-molecule compounds SB290157 and JR14a were obtained from MedChem Express (Cat. No: HY-101502A for SB290157; Cat. No: HY-138161 for JR14a).

Techniques:

Journal: Nature Communications

Article Title: Molecular basis of diverse ligand recognition and species-specific pharmacology at the complement anaphylatoxin receptor C3aR

doi: 10.1038/s41467-026-76518-z

Figure Lengend Snippet: A Structural comparison of SB290157 and JR14a binding pose to human and mouse C3aR. B Structural comparison of SB290157- and JR14a-bound C3aR structure with the inactive C5aR1 reveals activation-dependent structural changes, including the outwards movement of TM6, TM7 and Helix8. C , D SB290157/JR14a-induced cAMP response and βarr1 recruitment measured using the GloSensor assay and NanoBiT-based assay, respectively, upon stimulation of HEK-293 cells expressing the indicated receptor mutants. Data were normalized with the response for the wild-type treated as 100% (mean; n = 3 independent experiments). Comparison of ligand pharmacology of the above data are presented in Supplementary Tables . Source data are provided as a file.

Article Snippet: Small-molecule compounds SB290157 and JR14a were obtained from MedChem Express (Cat. No: HY-101502A for SB290157; Cat. No: HY-138161 for JR14a).

Techniques: Comparison, Binding Assay, Activation Assay, Expressing

Journal: Frontiers in Oncology

Article Title: Targeting MEST using cobicistat as a therapeutic strategy for gastric cancer through suppressing NF-κB signaling

doi: 10.3389/fonc.2026.1901635

Figure Lengend Snippet: Cobicistat was identified as a novel MEST inhibitor. (A) Eight binding pockets of MEST were identified using the SiteFinder module of MOE software. (B) Virtual docking screening of MEST inhibitor from a library. (C) A preliminary screening of 36 compounds was performed by SPR. (D) Binding affinity of the cobicistat to human MEST assessed by SPR. (E) Molecular structure of cobicistat small molecule. (F) Computational model and the interaction of cobicistat with MEST complex. (G) The interacting amino acids and hydrogen bonds between the complexes.

Article Snippet: Here, we identified a candidate MEST-inhibitory compound, cobicistat, by screening the TargetMol and Selleck small-molecule compound libraries based on its catalytic site, ASN163.

Techniques: Binding Assay, Software, Docking Assay, Screening

Journal: Journal of Pharmaceutical Analysis

Article Title: DT-TRAP enables accurate target recognition via simplified dosing and low-temperature incubation

doi: 10.1016/j.jpha.2026.101605

Figure Lengend Snippet: Dose-responsive target-responsive accessibility profiling (TRAP) identifies TEPP-46 targets in complex proteomes. (A) Volcano plots showing lysine accessibility changes in HeLa cell lysates. Each treatment group contained 100 μg of HeLa lysate and was treated with TEPP-46 at multiple concentrations (1 nM, 10 nM, 50 nM, 100 nM, 500 nM, 1 μM, 5 μM, and 10 μM), followed by ligand incubation for 1 h and TRAP labeling for 30 min, both performed at 25 °C. Thresholds were defined as TRAP ratio <0.5 or >2 with statistical significance assessed by one-way analysis of variance (ANOVA); ∗∗∗P < 0.001. (B) Dose-responsive accessibility changes at lysine residues K305/K311 of pyruvate kinase M2 (PKM2) upon TEPP-46 treatment, fitted using a four-parameter logistic (4 PL) model ( R 2 = 0.9951; n = 3 independent biological replicates). (C) Quantitative TRAP analysis of lysine-containing peptides within PKM2. Blue indicates TRAP peptides exhibiting the strongest accessibility changes, while cyan denotes peptides showing weaker or inconsistent changes ( n = 3 independent biological replicates). (D) Crystal structure of PKM2 (PDB: 3U2Z ) showing TEPP-46 (yellow) bound near the K305/K311 region. The TRAP-identified peptide segment exhibiting altered accessibility (K305/K311) is highlighted in blue, whereas non-responsive peptides are shown in cyan. PDB: protein data bank.

Article Snippet: The small-molecule compounds TEPP-46, geldanamycin, staurosporine, and aspirin were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Incubation, Labeling

Journal: Journal of Pharmaceutical Analysis

Article Title: DT-TRAP enables accurate target recognition via simplified dosing and low-temperature incubation

doi: 10.1016/j.jpha.2026.101605

Figure Lengend Snippet: Target identification of TEPP-46 using two- and three-dose target-responsive accessibility profiling (TRAP) analyses. (A) Quadrant plot showing proteins with consistent lysine accessibility changes in HeLa cell lysates. Each group contained 100 μg of HeLa cell lysate and was treated with TEPP-46 at 1 and 5 μM, followed by ligand incubation for 1 h at 25 °C and TRAP labeling for 30 min at the same temperature ( n = 3 independent biological replicates). Proteins with TRAP ratios (TEPP-46/control >2 or < 0.5) and statistical significance assessed by one-way analysis of variance (ANOVA; ∗∗∗ P < 0.001) were designated as potential targets. Accessibility decreases and increases are highlighted in blue and red, respectively. Each protein is represented by the peptide with the highest TRAP score. (B) Three-dimensional scatter plot showing shared targets across three doses of TEPP-46 (1, 5, and 10 μM). Drug incubation and TRAP labeling conditions were identical to those described in (A). Pyruvate kinase M2 (PKM2) was identified as the only consistent target (red) under statistical thresholds (TRAP ratio >2 or < 0.5; one-way ANOVA; ∗∗∗ P < 0.001). (C) Crystal structure of PKM2 (PDB: 3U2Z ) showing TEPP-46 (yellow) binding and corresponding lysine accessibility changes. The TRAP-identified peptide containing residues K305/K311 is highlighted in blue, whereas non-responsive peptides are shown in cyan, statistical significance assessed by one-way ANOVA (∗∗∗ P < 0.001, ∗∗∗∗ P < 0.0001). PDB: protein data bank.

Article Snippet: The small-molecule compounds TEPP-46, geldanamycin, staurosporine, and aspirin were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Drug discovery, Incubation, Labeling, Control, Binding Assay