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Synthetic chemistry processes may change for batch scale-up, and improvements or changes in compound purity and crystallinity may affect PK exposures in animals

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The downstream effects most consistently described in the literature: induction of collagen I and III, elastin, and decorin synthesis (Maquart et al., FEBS Letters , 1988), upregulation of VEGF and basic FGF transcripts, induction of antioxidant defense genes including SOD2 and metallothionein isoforms, and modulation of the MMP-2 and TIMP-1/2 balance toward non-fibrotic remodeling