compounds of microsource discovery's mssp library  (MicroSource Discovery Systems)

Journal: British Journal of Pharmacology

Article Title: Identification through high-throughput screening of 4'-methoxyflavone and 3',4'-dimethoxyflavone as novel neuroprotective inhibitors of parthanatos

doi: 10.1111/bph.12201

Figure Lengend Snippet: Flow chart for the screening project. Assay was developed and optimized in HeLa cells and then employed for high-throughput screen of two chemical libraries: the MSSP Library and the JHDL. AB (fluorescence-based) or CTG (luminescence-based) was used to quantify cell viability. Compounds showing toxicity were rescreened at 2 and 5 μM while those with marginal protective effects were rescreened at 20 μM. The 10 hits from the primary screen were rescreened for validation. One compound was confirmed as true hit. A number of small molecules belonging to the same class as this compound or similar classes were then selected and screened, resulting in one more hit that was then validated. Dose–response data were obtained for the two hits; they were proven to block the synthesis and accumulation of toxic PAR polymer and were also neuroprotective in cell culture. They are now to be investigated for their ability to afford neuroprotection in animal models of neuronal death.

Article Snippet: MSSP Library (2 mM) was purchased from the Johns Hopkins ChemCORE Facility (10 mM stock was originally purchased from MicroSource Discovery Inc., Groton, CT, USA).

Techniques: High Throughput Screening Assay, Fluorescence, Biomarker Discovery, Blocking Assay, Polymer, Cell Culture

Journal: British Journal of Pharmacology

Article Title: Identification through high-throughput screening of 4'-methoxyflavone and 3',4'-dimethoxyflavone as novel neuroprotective inhibitors of parthanatos

doi: 10.1111/bph.12201

Figure Lengend Snippet: Flow chart for the screening project. Assay was developed and optimized in HeLa cells and then employed for high-throughput screen of two chemical libraries: the MSSP Library and the JHDL. AB (fluorescence-based) or CTG (luminescence-based) was used to quantify cell viability. Compounds showing toxicity were rescreened at 2 and 5 μM while those with marginal protective effects were rescreened at 20 μM. The 10 hits from the primary screen were rescreened for validation. One compound was confirmed as true hit. A number of small molecules belonging to the same class as this compound or similar classes were then selected and screened, resulting in one more hit that was then validated. Dose–response data were obtained for the two hits; they were proven to block the synthesis and accumulation of toxic PAR polymer and were also neuroprotective in cell culture. They are now to be investigated for their ability to afford neuroprotection in animal models of neuronal death.

Article Snippet: MSSP Library (2 mM) was purchased from the Johns Hopkins ChemCORE Facility (10 mM stock was originally purchased from MicroSource Discovery Inc., Groton, CT, USA).

Techniques: High Throughput Screening Assay, Fluorescence, Biomarker Discovery, Blocking Assay, Polymer, Cell Culture