Journal: Frontiers in Pharmacology

Article Title: Protein-protein interaction-based high throughput screening for adenylyl cyclase 1 inhibitors: Design, implementation, and discovery of a novel chemotype

doi: 10.3389/fphar.2022.977742

Figure Lengend Snippet: Pilot screen individual library results. All pilot screen assays used concentrations of AC1 and CaM shown in . The dotted line representing the vehicle is beneath the cluster of compounds screened (black circles). 100 μM CDZ is shown as the dotted line labeled as positive control. Polarization values correspond to well positions for plates within the library tested. (A) FDA-approved library, (B) MicroSource Spectrum (MMSP) library, (C) ChemBridge DIVERSet library, (D) ChemDiv CNS library.

Article Snippet: The Microsource spectrum collection (MMSP) (Microsource Discovery Systems, Gaylordsville, CT) was screened as outlined above for the FDA-approved library with some minor differences.

Techniques: Labeling, Positive Control

Journal: Frontiers in Pharmacology

Article Title: Protein-protein interaction-based high throughput screening for adenylyl cyclase 1 inhibitors: Design, implementation, and discovery of a novel chemotype

doi: 10.3389/fphar.2022.977742

Figure Lengend Snippet: Concentration response curves (A) and structures (B) for FDA-approved and MMSP library hits. Each hit was used to generate CRCs in the AC1-C1b/CaM (blue circles), AC8-Nt/CaM (red squares), and AC8-C2b/CaM (green triangles) FP assays. (B) The structures for each hit are shown with the hit number and the given compound name. Data is normalized to vehicle (100% maximum polarization) and 100 μM CDZ (0% polarization). All data represents n = 3 experiments ±SE.M.

Article Snippet: The Microsource spectrum collection (MMSP) (Microsource Discovery Systems, Gaylordsville, CT) was screened as outlined above for the FDA-approved library with some minor differences.

Techniques: Concentration Assay

Journal: Frontiers in Pharmacology

Article Title: Protein-protein interaction-based high throughput screening for adenylyl cyclase 1 inhibitors: Design, implementation, and discovery of a novel chemotype

doi: 10.3389/fphar.2022.977742

Figure Lengend Snippet: AC1/CaM pilot screen CRC analysis. IC 50 and % inhibition relative to 100 μM CDZ (100% inhibition) obtained for each compound in the AC1/CaM FP assay. The Ki values obtained with experimentally determined K D values for each AC/CaM FP assay and the IC 50 values obtained for each compound in the designated AC/CaM FP assay. The final two columns show the K i ratios obtained for either AC8-Nt/CaM or AC8-C2b/CaM over AC1/CaM. Values with K i ratios greater than 1 were more potent in the AC1/CaM FP assay over the designated AC8/CaM FP assay. All data represents n = 3 experiments, ± CI for AC1/CaM IC 50 values.

Article Snippet: The Microsource spectrum collection (MMSP) (Microsource Discovery Systems, Gaylordsville, CT) was screened as outlined above for the FDA-approved library with some minor differences.

Techniques: Inhibition, FP Assay, Drug discovery