Journal: Journal of Medicinal Chemistry

Article Title: Discovery of Sulfonamide Pantothenate Kinase Activators and Elucidation of the Role of Isoform Selectivity in Cellular Pantothenate Kinase Activation

doi: 10.1021/acs.jmedchem.5c03452

Figure Lengend Snippet: Binding site view of the PZ-3022 (1) PANK3 AMP-PNP complex (PDB ID: 6PE6 ) showing the spatial proximity of the cyclopropyl to the ATP-binding pocket of the enzyme. B) Pantazine PZ-3890 CoA elevation dose response in human C3A cells demonstrating a “hook effect” and an optimal activity window of 1–30 μM for this compound.

Article Snippet: Human C3A (HepG2/C3A) cells (ATCC CRL-10741) were used for cellular assays.

Techniques: Binding Assay, Activity Assay

Journal: Journal of Medicinal Chemistry

Article Title: Discovery of Sulfonamide Pantothenate Kinase Activators and Elucidation of the Role of Isoform Selectivity in Cellular Pantothenate Kinase Activation

doi: 10.1021/acs.jmedchem.5c03452

Figure Lengend Snippet: Correlation Analysis and Surface Plasmon Resonance. A. Correlation analysis of the difference between K i of PANK1β and PANK3 vs C3A CoA elevation. The green-to-red scale shows the difference in K i between PANK1β and PANK3, while the size of the circles indicates the level of CoA elevation. B–E Surface Plasmon Resonance trace showing the binding of 20 and 21 to PANK3 and PANK1β in the presence of 1 mM ATP. B. 20 with PANK3. C. 20 with PANK1β. D. 21 with PANK3. E. 21 with PANK1β. The green data line was fit to a kinetic model shown in the black line. The association ( K a ), dissociation ( K d ), binding equilibrium ( K D ) constants, residence time (RT), and response units (RU) are shown in each panel.

Article Snippet: Human C3A (HepG2/C3A) cells (ATCC CRL-10741) were used for cellular assays.

Techniques: SPR Assay, Binding Assay

Journal: Redox Biology

Article Title: The C3–C3aR axis drives rotenone-induced cognitive damage via synaptic engulfment, dark microglia and PANoptosis

doi: 10.1016/j.redox.2026.104062

Figure Lengend Snippet: Inhibition of C3aR ameliorates rotenone-induced neurodegeneration, synaptic loss, α-synuclein phosphorylation and cognitive deficits in mice. C57BL/6 mice were treated with rotenone for 3 weeks to establish PD models, with 30 min of SB290157 (C3aR inhibitor, 1 mg/kg, i.p.) administration after each rotenone injection. (A) Concentrations of C3a in the hippocampus of Con and Rot mice, measured by enzyme-linked immunosorbent assay (ELISA). n = 6. (B) Representative Western blot images and densitometric quantification of C3aR protein levels in the hippocampus and rotenone mice. n = 4. (C) The mRNA levels of C3aR in vehicle and rotenone mice. (D) Representative images of double-immunofluorescence staining with C3aR and Iba-1 or Neu-N antibodies and (E, F) the quantification of C3aR + Iba-1 + and C3aR + Neu-N + cells in vehicle and rotenone mice. n = 3. (G) The quantification of Neu-N + cell number and (H) optical density of PSD95 staining in rotenone mice with or without C3aR inhibitor treatment. (I) The representative images of Neu-N and PSD95 staining in rotenone mice with or without C3aR inhibitor treatment. n = 6. (J, K) Representative bands of Neu-N, PSD95 and ser129-phosphorylated α-synuclein and the quantification of blots in rotenone mice with or without C3aR inhibitor treatment. n = 4. (L) Representative images of ser129-phosphorylated α-synuclein and (M) the quantification of staining density in rotenone mice with or without C3aR inhibitor treatment. n = 3. (N–Q) Escape latency, traveled distance, first platform crossing latency and platform crossing number in rotenone mice with or without C3aR inhibitor treatment. n = 15; ∗ p < 0.05, ∗∗ p < 0.01 for comparison between Rot & Rot + C3aR inhibitor groups; Scale bar = 50 μm.

Article Snippet: The C3a ELISA kit was purchased from CUSABIO (CSB- E08511 m, Houston, TX, USA), and TUNEL assay kit was provided by KeyGEN (KGA7073-1, Nanjing, China.

Techniques: Inhibition, Phospho-proteomics, Injection, Enzyme-linked Immunosorbent Assay, Western Blot, Double Immunofluorescence Staining, Staining, Comparison