RGLS4326

RGLS4326 (RG4326) is a first-in-class, short oligonucleotide inhibitor of microRNA-17 (miR-17). RGLS4326 can be used for the research of autosomal dominant polycystic kidney disease (ADPKD). RGLS4326 inhibits miR-17 function in HeLa cells with an EC50 value of 28.3 nM[1].

RGLS4326, a single-stranded, chemically modified, short oligonucleotide of 9-nt with full complementarity to the miR-17 seed sequence. RGLS4326 inhibits the pathologic functions of the miR-17 family of miRNAs in ADPKD[1]. RGLS4326 treatment inhibits miR-17 function in kidney collecting duct cells in culture as measured by miR-17 PD-Sig, with an EC50 value of 77.2 ± 20.2 nM[1].RGLS4326 suppresses the growth of primary human autosomal dominant polycystic kidney disease (ADPKD) cysts[1].

RGLS4326 preferentially distributes to kidney tubules and cysts. RGLS4326 (a single 30 mg/kg SC injection) is rapidly absorbed into plasma, showing Tmax of ≤1 h, Cmax of 8.5 µg/mL, and half-life of <4 h in wild-type mice[1].In vivo administration of RGLS4326 also upregulates the expression of the direct miR-17 target genes Pkd1 and Pkd2[1].

[1]. Edmund C Lee, et al. Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease. Nat Commun. 2019 Sep 12;10(1):4148.