[CAS NO. 2229964-07-0] RGLS4326
PRODUCTS SPECIFICATIONS [2229964-07-0]
DESCRIPTION [2229964-07-0]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 3082.42 |
| Molecular Formula | C95H115F3N32O51P8S8 |
| SMILES | [RGLS4326] |
Summary
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 EC 50 value of 28.3 nM [1] .
IC50 & Target
MicroRNA [1]
In Vitro
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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. |
In Vivo
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT04536688 | Regulus Therapeutics Inc. |
Polycystic Kidney Disease, Autosomal Dominant
|
October 13, 2020 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
