RGLS4326 (RG4326) is a short oligonucleotide inhibitor of microRNA-17 (miR-17), with a pioneering role in its class. This compound, with a research focus on autosomal dominant polycystic kidney disease (ADPKD), effectively suppresses the activity of miR-17 in HeLa cells, displaying an EC50 value of 28.3 nM.

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 EC 50 value of 77.2?±?20.2?nM[1]. RGLS4326 suppresses the growth of primary human autosomal dominant polycystic kidney disease (ADPKD) cysts[1]. Cell Proliferation Assay[1]Cell Line: Primary cysts in 3D Matrigel Concentration: 5, 20, 100, and 300? nM Incubation Time: 9 days Result: Decreased in cyst epithelial cell proliferation.

RGLS4326 preferentially distributes to kidney tubules and cysts. RGLS4326 (a single 30?mg/kg SC injection) is rapidly absorbed into plasma, showing T max of ≤1?h, C max 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]. Animal Model: Pkd2 -KO mice[1]Dosage: 20?mg/kg Administration: SC injection Result: Compared to non-cystic control kidneys, polycystic kidneys of PBS-treated Pkd2 -KO mice exhibit an age-dependent progressive decline in miR-17 PD-Sig, indicative of increasing miR-17 activity with disease progression. Administration of RGLS4326 reversed this decline in miR-17 PD-Sig, indicating a sustained functional inhibition of miR-17.