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TSA can also inhibit the expression of the HAS2/FGF9 axis, alleviating hypoxia-induced apoptosis in AC16 cardiomyocytes (reducing Cleaved Caspase-3 and Bax expression), inflammation (reducing IL-6, IL-1 and TNF-) and oxidative damage (reducing MDA levels) (123)

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Epacadostat, a highly potent IDO1 inhibitor, despite its initial promise in preclinical settings, demonstrated no clinical benefit in combination with the PD-1 inhibitor pembrolizumab in a large Phase III trial (NCT02752074), possibly due to compensatory mechanisms such as upregulation of IDO2 and tryptophan-2,3-dioxygenase (TDO), which sustains immunosuppressive kynurenine production (55)

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Both ACSL4 and LPCAT3 are key regulators of lipid metabolism and play a role in iron activation