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Additional phylogenetic analyses were performed using the Maximum Likelihood method based on the Jones-Taylor-Thornton (JTT) matrix-based model (Jones et al., 1992), which gave overall similar results (Figure S1B)

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Whereas, hydrophobic small molecules frequently failed on the road toward clinical use, due to variable and complexed problems including bio-availability, and swift clearance, which in turn because of their physicochemical nature