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. 2023 Oct 2;20(6):1779–1795. doi: 10.1007/s13311-023-01444-7

Fig. 1.

Fig. 1

The drug discovery process of the combinatorial drugs for ALS. Data analysis predicted 627 single drugs of the 1834 single drugs. Two hundred five single drugs with a high probability of the 627 in data analysis were tested for the primary screening, and 18 single drugs were effective in anti-inflammation and neurogenesis. For the secondary screening, 100 combinatorial drugs, composed of 2 single drugs showing a significant effect in primary screening were tested. Fourteen combinatorial drugs from secondary screening show an excellent effect on inflammation and neurogenesis with a synergistic effect compared to the single drugs. Finally, nebivolol-HCl and donepezil-HCl (nebivolol-donepezil) were selected, and the drugs’ therapeutic effect was validated in vitro and in vivo