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sepiapterin Sepiapterin is a natural precursor of the enzymatic co-factor BH4, a critical co-factor for phenylalanine hydroxylase (PAH). Sepiapterin acts as a dual pharmacological chaperone (sepiapterin and BH4 each with its own binding affinity to variant PAH), including PAH variants commonly found in PKU and known to be insensitive to BH4, to improve the activity of the defective PAH enzyme, achieving a high concentration of BH4 intracellularly. By enhancing the conformational stability of misfolded PAH enzyme and increasing the intracellular concentrations of BH4, sepiapterin is able to effectively reduce blood Phe levels.

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