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RGLS4326

Catalog No. T39712 CAS 2229964-07-0

Synonyms: RG4326, RGLS4326

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.

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RGLS4326, CAS 2229964-07-0

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Description	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.
In vitro	RGLS4326, a chemically modified, single-stranded oligonucleotide of 9 nucleotides (nt) fully complementary to the miR-17 seed sequence, effectively inhibits the adverse functions associated with the miR-17 family of microRNAs (miRNAs) in autosomal dominant polycystic kidney disease (ADPKD)[1]. This inhibition extends to the function of miR-17 in cultured kidney collecting duct cells, where its activity is significantly reduced, as evidenced by the miR-17 PD-Sig, with an efficacy concentration (EC 50) of approximately 77.2 ± 20.2 nM[1]. Additionally, RGLS4326 demonstrates the capability to suppress the growth of primary human ADPKD cysts[1]. In a Cell Proliferation Assay conducted on primary cysts within a 3D Matrigel environment at various concentrations (5, 20, 100, and 300 nM) over nine days, it was observed that RGLS4326 leads to a decrease in the proliferation of cyst epithelial cells[1].
In vivo	RGLS4326 exhibits a preference for targeting kidney tubules and cysts. Administered as a single subcutaneous (SC) injection at 30mg/kg, it achieves rapid plasma absorption with a peak concentration (T max) of ≤1 hour, a maximum concentration (C max) of 8.5μg/mL, and a short half-life of <4 hours in wild-type mice[1]. This compound notably increases the levels of Pkd1 and Pkd2 genes, direct targets of miR-17, upon in vivo administration[1]. In a study involving Pkd2 knockout (Pkd2 -KO) mice[1] treated with 20mg/kg RGLS4326 via SC injection, a marked difference was observed in polycystic kidneys when compared to non-cystic control kidneys. Specifically, in the placebo (PBS)-treated Pkd2-KO mice, there was a progressive, age-dependent increase in miR-17 activity, as evidenced by a drop in miR-17 pharmacodynamic signal (PD-Sig), correlating with disease progression. Conversely, treatment with RGLS4326 led to a reversal of this trend, effectively indicating sustained functional inhibition of miR-17.

Synonyms	RG4326, RGLS4326
Molecular Weight	3082.4
Formula	C95H115F3N32O51P8S8
CAS No.	2229964-07-0

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

References and Literature

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.

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Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

RGLS4326 2229964-07-0 RGLS-4326 RG4326 RG-4326 RGLS 4326 RG 4326 inhibitor inhibit

Products are chemical reagents for research use only and are not intended for human use. We do not sell to patients.