5-C-phenethyl-DNJ (hydrochloride) is an orally active acidic α-glucosidase (GAA) activator. It enhances GAA activity in various tissues, with a notable effect in the diaphragm. This compound is useful for researching metabolic disorders, such as Pompe disease.

5-C-phenethyl-DNJ (hydrochloride) (Compound 4c) acts as a specific inhibitor of recombinant human acid α-glucosidase (rhGAA) with an IC 50 of 0.81 μM. At a concentration of 100 μM, this compound significantly enhances the stability of rhGAA at neutral pH (7.4) and maintains its structural stability in plasma and non-lysosomal cellular compartments. With concentrations ranging from 0.1-100 μM over 30-60 minutes, it demonstrates exceptional selectivity for human glycosidases, with IC 50 values exceeding 100 μM for GANAB, GBA1, and GBA2. Additionally, at concentrations of 5-20 μM over 24 hours, 5-C-phenethyl-DNJ (hydrochloride) significantly restores the activity of endogenous GAA in fibroblasts derived from Pompe disease patients harboring various GAA mutations. At 20 μM over 24 hours, it also enhances the activity and lysosomal delivery of rhGAA in Pompe disease fibroblasts.

The compound 5-C-phenethyl-DNJ (hydrochloride) (Compound 4c), administered orally at 5 mg/kg once daily for four consecutive days, significantly increased the activity of rhGAA in the tissues of GAA knockout mice.