BF844 is a chemical compound that demonstrates the ability to mitigate hearing loss in individuals with Usher Syndrome Type III (USH3) caused by the CLRN1 mutation (specifically N48K). One of its mechanisms of action is the transportation of CLRN1 N48K to the plasma membrane. In vivo studies have shown that BF844 significantly preserves hearing [1].

BF844 (compound 3) (0.846 μM) effectively inhibits HSP60 activity (87.07±27.70% inhibition) and moderately inhibited HSP90 (40.06±19.10% inhibition) [1]. BF844 (2.90 μM; 24 h) induces about 6% of total CLRN1 N48K to be transported to the plasma membrane in C1, D1, D6 cells [1]. BF844 (2.90 μM; 24 h) effectively increases the amount of non-glycosylated CLRN1 and non-glycosylated CLRN1 is effectively transported to the plasma membrane in C1 and D1 cells [1].

BF844 shows good penetration into the retina and cochlea in vivo [1]. BF844 (10 mg/kg; i.p.) shows significantly preserves hearing in Tg;KI/KI mice [1]. Animal Model: Juvenile mice [1] Dosage: 3, 10 mg/kg (3 mg/kg for P6 (post-natal day 6) mice, 10 mg/kg for P20 (post-natal day 20) mice) Administration: I.p. Result: Showed AUC values were determined to be 1.76 μM.h and 1.98 μM.h. Animal Model: P30 Tg;KI/KI C57BL/6J mice [1] Dosage: 30 mg/kg Administration: I.p.; daily from P30 to P45 Result: Showed significantly preserves hearing with the median threshold of sound intensity in log scale was 57.5–67.5 dB SPL and about 1,000 times more sensitive hearing compared to untreated controls at P55. Animal Model: P10 Tg;KI/KI C57BL/6J mice [1] Dosage: 10 mg/kg Administration: I.p.; 10 mg/kg every other day and gradually escalated the dose up to 20 mg/kg at P28. From P30 to P45, mice received 30 mg/kg daily Result: Showd the median threshold of sound intensity in log scale was 55, 42.5 and 37.5 dB SPL lower at 8, 16 and 32 kHz at P55, respectively.