RGLS4326 sodium
Based on 1 publication(s) in Google Scholar
RGLS4326 (RG4326) sodium is a microRNA-17 (miR-17) oligonucleotide inhibitor with an EC50 of 28.3 nM. RGLS4326 sodium antagonizes AMPAR and inhibits ligand binding. RGLS4326 sodium relieves the inhibition of Pkd1/Pkd2 by miR-17 and upregulates PC1/PC2. RGLS4326 sodium preferentially distributes to the kidney and cysts, attenuates cyst progression and improves survival in mouse models of autosomal dominant polycystic kidney disease (ADPKD) in a miR-17 binding motif-dependent manner. RGLS4326 sodium can be used in ADPKD-related research.
For research use only. We do not sell to patients.
- Purity : 99.67%
- Molecular Weight:3082.42 (free acid)
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Storage:
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Biological Activity
Description
In Vitro
RGLS4326 sodium competitively antagonizes human GluA1/GluA4 AMPAR in HEK293 cells with Kb = 163 nM[1].
RGLS4326 sodium inhibits the function of GluA2-homotetrameric AMPARs in HEK293 cells[1].
RGLS4326 (200 µM; 30 min) sodium binds GluA2-γ2 LBD via 3’G, stabilizes the open clamshell/closed pore state, and provides the structural basis for competitive AMPAR inhibition[1].
RGLS4326 (10-100 μM; 90 min) sodium is a cell-free AMPA receptor ligand that inhibits [3H]-AMPA binding with an IC50 <10 μM through its 3'-terminal guanine[1].
RGLS4326 (100 μM) sodium derepresses Pkd1/Pkd2 and inhibits 3D cyst growth in Pkd1RC/- mouse collecting duct-derived cells[2].
RGLS4326 sodium shows no in vitro genotoxicity or mitochondrial toxicity in bacterial mutagenicity, human lymphocyte micronucleus, and human cell assays[3].
RGLS4326 sodium inhibits miR-17 and de-represses Pkd1/Pkd2 in mouse kidney collecting duct cells with an EC50 of 77.2 nM[3].
RGLS4326 (5-10 μM; 24-72 h) sodium derepresses miR-17 PD-Sig in isolated mouse kidney slices and shows low pro-inflammatory gene induction in rat tissue slices[3].
RGLS4326 (8 days) sodium derepresses miR-17 targets, increasing PC1 by approximately 2-fold and PC2 by approximately 4-fold, and reduces cyst growth in primary human ADPKD cyst cultures[3].
RGLS4326 sodium retains targeted anti-miR-17 activity in in vitro ADPKD models, de-represses PKD1/PKD2, and reduces cyst growth[1].
RGLS4326 sodium is metabolically stable in mouse, monkey, and human tissue lysates[3].
RGLS4326 (10 μM; 24 h) sodium inhibits miR-17 and derepresses the miR-17 luciferase sensor in HeLa cells with an EC50 of 28.3 nM[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Ex vivo mouse kidney slices
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Concentration:10 μM
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Incubation Time:72 h
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Result:De-repressed miR-17 PD-Sig in ex vivo mouse kidney slices.
RNA extraction and qRT-PCR analysis revealed a consistent shift in the characteristic expression profiles of target genes, which was consistent with the restoration of the miR-17 pathway.
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Cell Line:Rat liver and kidney sections
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Concentration:5 μM
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Incubation Time:24 and 48 h
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Result:Following RNA extraction, qRT-PCR analysis revealed only low-level induction of the pro-inflammatory gene panel in both tissues.
Did not elicit robust upregulation of Il1b, Tnf, or Ccl2 relative to Vehicle-treated slices.
In Vivo
RGLS4326 (20 mg/kg; s.c.; injected on postnatal days P8, P10, P12, and P15 (4 doses)) sodium shows in vivo activity similar to that of RGLS8429 (HY-150364) in the Pkd1F/RC ADPKD mouse model, significantly alleviating kidney enlargement, cyst progression, cell proliferation, and renal function impairment[1].
RGLS4326 (20 mg/kg; s.c.; injected at P10-P16) sodium almost prevents PKD and preserves renal function by P18 in KspCre; Pkd1F/RC mice[2].
RGLS4326 (20 mg/kg; s.c.; injected at P16-P17) sodium attenuates PKD progression and stabilizes renal function by P26 in KspCre; Pkd1F/RC mice[2].
RGLS4326 (20 mg/kg; subcutaneous injection; at P16-P17, then weekly or biweekly until 18 weeks of age) sodium improves survival and preserves renal parenchyma by 18 weeks in KspCre; Pkd1F/RC mice[2].
RGLS4326 (30 mg/kg; s.c.; single dose) sodium persistently displaces renal miR-17 from translationally active polysomes in normal mice[3].
RGLS4326 (30 mg/kg; s.c.; single dose) sodium inhibits renal miR-17 in the JCK/C57BL6 PKD and Pcy/CD1 PKD models[3].
RGLS4326 (20 mg/kg; s.c.; injected on postnatal days 10-19) sodium inhibits miR-17 and reduces cystic kidney disease progression in Pkd2-KO mice[3].
RGLS4326 (25 mg/kg; s.c.; QW or Q4W; 25 weeks) sodium reduces cyst burden in Pcy/CD1 mice when administered early, whereas late intervention is ineffective[3].
RGLS4326 (1-25 mg/kg; s.c.; QW; 9 weeks) sodium dose-dependently reduces kidney weight-to-body weight ratio and cyst index in Pcy/DBA mice, whereas monthly dosing is ineffective[3].
RGLS4326 (30 mg/kg; s.c.; QW; 8 weeks) sodium slows the increase in kidney volume measured by MRI in Pcy/DBA mice[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL6[1]
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Dosage:0.003, 0.03, 0.3, 3, 30, or 300 mg/kg
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Administration:s.c.; single injection
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Result:Showed stronger target engagement in kidney (≥75% for 14 days) than in liver (≤75% by 7 days).
Exhibited similar potency in the kidney.
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Animal Model:Ksp/Cre; Pkd1F/RC (postnatal day 8-18)[1]
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Dosage:20 mg/kg
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Administration:s.c.; on postnatal days P8, P10, P12, and P15 (4 doses)
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Result:Showed a similar efficacy profile to RGLS8429 in the Pkd1F/RC ADPKD mouse model after repeat s.c. dosing at 20 mg/kg.
Resulted in a significant reduction in KW/BW, the cyst index, the proliferation index, and BUN levels, and improved renal pathological morphology.
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Animal Model:KspCre; Pkd1F/RC (C57BL/6J background; equal numbers of males and females)[2]
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Dosage:20 mg/kg
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Administration:subcutaneous injection; on P10, P11, P12, and P16
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Result:By P18, PKD was virtually prevented, and renal function remained normal in Pkd1RC/- mice.
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Animal Model:KspCre; Pkd1F/RC (C57BL/6J background; equal numbers of males and females)[2]
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Dosage:20 mg/kg
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Administration:subcutaneous injection; on P16 and P17
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Result:By P26, Pkd1RC/- mice exhibited attenuation of PKD progression and stabilization of kidney function.
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Animal Model:KspCre; Pkd1F/RC (C57BL/6J background; equal numbers of males and females)[2]
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Dosage:20 mg/kg (weekly); 20 mg/kg (semimonthly)
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Administration:subcutaneous injection; on P16 and P17, then weekly until 18 weeks of age; or subcutaneous injection; on P16 and P17, then every other week (semimonthly) until 18 weeks of age
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Result:70% (7/10) of mice receiving every-other-week dosing and 50% (5/10) of mice receiving weekly dosing survived until 18 weeks of age.
Surviving mice had substantially preserved kidney parenchyma and reduced KW/BW.
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Animal Model:C57BL/6 (WT/C57BL6)[3]
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Dosage:30 mg/kg
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Administration:s.c.; single dose
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Result:Seven days after a single 30 mg/kg s.c. dose, kidney miR-17 displacement miPSA score was 3.16, representing 89% inhibition.
Displacement began within 24 h, peaked at day 7, and continued for at least 14 days.
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Animal Model:C57BL/6 (JCK/C57BL6)[3]
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Dosage:30 mg/kg
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Administration:s.c.; single dose
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Result:Seven days after a single 30 mg/kg s.c. dose, kidney miR-17 displacement miPSA score was 2.58, representing 83% inhibition.
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Animal Model:CD-1 (Pcy/CD1)[3]
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Dosage:30 mg/kg
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Administration:s.c.; single dose
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Result:Seven days after a single 30 mg/kg s.c. dose, kidney miR-17 displacement miPSA score was 2.56, representing 83% inhibition.
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Animal Model:Pkhd1/cre;Pkd2F/F (Pkd2-KO)[3]
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Dosage:20 mg/kg
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Administration:s.c.; postnatal days 10, 11, 12, and 19
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Result:Reversed the age-dependent decline in miR-17 PD-Sig, upregulated Pkd1 and Pkd2 expression, reduced kidney-to-body-weight ratio, and decreased cyst epithelial cell proliferation.
Kidney RNA-seq showed global de-repression of predicted miR-17 target genes and improved expression of 994 genes; Spearman rho = -0.559.
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Animal Model:CD-1 (Pcy/CD1)[3]
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Dosage:25 mg/kg
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Administration:s.c.; QW or Q4W; 25 consecutive weeks; QW; 15 consecutive weeks (late intervention)
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Result:Weekly or monthly dosing reduced kidney-to-body-weight ratio, cyst index, urine Ngal protein, and kidney Ngal mRNA expression; late dosing did not attenuate cyst growth.
Kidney RNA-seq showed improved expression of 658 genes;.
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Animal Model:DBA/2 (Pcy/DBA)[3]
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Dosage:1, 5 and 25 mg/kg (QW for 9 weeks); 25 mg/kg (Q4W for 9 weeks)
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Administration:s.c.; QW or Q4W; 9 consecutive weeks
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Result:Weekly dosing produced dose-dependent reductions in kidney-to-body-weight ratio and cyst index; monthly dosing did not confer efficacy.
Tolvaptan reduced kidney-to-body-weight ratio but did not improve cyst index.
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Animal Model:DBA/2 (Pcy/DBA)[3]
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Dosage:30 mg/kg
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Administration:s.c.; QW; 8 consecutive weeks
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Result:bwTKV increased almost linearly in PBS control mice, whereas kidney growth plateaued after only 4 weeks of dosing; 1 of 10 mice receiving weekly dosing showed stabilization and 2 of 10 showed reduction of bwTKV.
MRI-based TKV showed a 50% reduction in bwTKV.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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Appearance Solid
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Molecular Weight 3082.42 (free acid)
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Color White to off-white
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SMILES
[RGLS4326 (sodium)]
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Synonyms
RG4326 sodium
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Publications (1)
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Journal Impact Factor
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Most Recent
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RGLS4326 sodium purchased from MedChemExpress. Usage Cited in: Patent. US20250283086A1.
PC1 protein analysis in PPMO-treated WT9-7 cells. WT9-7 cells were incubated with PPMOs with the sequences corresponding to SEQ ID NO:47 (+604+628) in quadruplicate and a non-targeting control (NTC) for 2, 3 or 5 days. A non-targeting control (NTC) was used as a negative control and an inhibitor of miR-17 (RGLS4326), was included as a positive control.
RGLS4326 sodium purchased from MedChemExpress. Usage Cited in: Patent. US20250283086A1.
Western blot images of PPMO-treated HEK293 cells. HEK293 cells were treated with PPMOs (+604+628) and (+611+635) with the sequences corresponding to SEQ ID NOs:47, and 334, respectively. A non-targeting control (NTC) was used as a negative control while an inhibitor of miR-17 (RGLS4326), was included as a positive control. PPMO-treated cells were harvested at 5 days and analysed for PC1 expression using western blot assay.
Purity & Documentation
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Data Sheet (294 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2242 KB)
References
[1]. Valencia T, et al. The nucleobase guanine at the 3'-terminus of oligonucleotide RGLS4326 drives off-target AMPAR inhibition and CNS toxicity. Nature communications. 2025 Nov 28;16(1):10762. [Content Brief]
[3]. Lee EC, et al. Discovery and preclinical evaluation of anti-miR-17 oligonucleotide RGLS4326 for the treatment of polycystic kidney disease. Nature communications. 2019 Sep 12;10(1):4148. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
RGLS4326 sodium Related Classifications
HY-139290A Related Classifications
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