RGLS4326
Based on 1 publication(s) in Google Scholar
RGLS4326 (RG4326) is a microRNA-17 (miR-17) oligonucleotide inhibitor with an EC50 of 28.3 nM. RGLS4326 antagonizes AMPAR and inhibits ligand binding. RGLS4326 relieves the inhibition of Pkd1/Pkd2 by miR-17 and upregulates PC1/PC2. RGLS4326 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 can be used in ADPKD-related research.
For research use only. We do not sell to patients.
- Purity : 99.06%
- CAS No.: 2229964-07-0
- Formula: C95H115F3N32O51P8S8
- Molecular Weight:3082.42
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Storage:
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) RGLS4326
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Biological Activity
Description
In Vitro
RGLS4326 inhibits the function of GluA2-homotetrameric AMPARs in HEK293 cells[1].
RGLS4326 (200 µM; 30 min) 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 (5-10 μM; 24-72 h) 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) 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 is metabolically stable in mouse, monkey, and human tissue lysates[3].
RGLS4326 (10 μM; 24 h) 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)) 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) 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) 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) improves survival and preserves renal parenchyma by 18 weeks in KspCre; Pkd1F/RC mice[2].
RGLS4326 (30 mg/kg; s.c.; single dose) persistently displaces renal miR-17 from translationally active polysomes in normal mice[3].
RGLS4326 (30 mg/kg; s.c.; single dose) 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) 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) 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) 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) 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.
Chemical Information
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CAS No. 2229964-07-0
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Appearance Solid
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Molecular Weight 3082.42
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Formula C95H115F3N32O51P8S8
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Color White to off-white
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SMILES
OC[C@@]1(O[C@@H](N2C3=NC=NC(N)=C3N=C2)[C@]4([H])O[C@H]1C)[C@H]4OP(OC[C@]56[C@H]([C@](O[C@H]6C)([H])[C@H](N7C8=C(C(N=C(N8)N)=O)N=C7)O5)OP(OC[C@@H]9[C@H]([C@H]([C@H](N%10C(N=C(C=C%10)N)=O)O9)OC)OP(OC[C@@H]%11[C@H]([C@H]([C@H](N%12C%13=NC=NC(N)=C%13N=C%12)O%11)F)OP(OC[C@@H]%14[C@H]([C@H]([C@H](N%15C(N=C(C=C%15)N)=O)O%14)F)OP(OC[C@@H]%16[C@H]([C@H]([C@H](N%17C(NC(C=C%17)=O)=O)O%16)F)OP(OC[C@@H]%18[C@H]([C@H]([C@H](N%19C(NC(C=C%19)=O)=O)O%18)OC)OP(OC[C@]%20%21[C@H]([C@](O[C@H]%21C)([H])[C@H](N%22C(NC(C=C%22)=O)=O)O%20)OP(OC[C@@]%23%24O[C@@H](N%25C%26=C(C(N=C(N%26)N)=O)N=C%25)[C@@](O[C@H]%24C)([H])[C@@H]%23O)(S)=O)(S)=O)(S)=O)(S)=O)(S)=O)(S)=O)(S)=O)(S)=O
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Synonyms
RG4326
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Sequence
5’-AsGsCmAfCfUfUmUsGs-3‘
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Publications (1)
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Journal Impact Factor
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Most Recent
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RGLS4326 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 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.
Solvent & Solubility
In Vitro:
H2O : ≥ 100 mg/mL (32.44 mM)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (323 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O | 1 mM | 0.3244 mL | 1.6221 mL | 3.2442 mL | 8.1105 mL |
| 5 mM | 0.0649 mL | 0.3244 mL | 0.6488 mL | 1.6221 mL | |
| 10 mM | 0.0324 mL | 0.1622 mL | 0.3244 mL | 0.8111 mL | |
| 15 mM | 0.0216 mL | 0.1081 mL | 0.2163 mL | 0.5407 mL | |
| 20 mM | 0.0162 mL | 0.0811 mL | 0.1622 mL | 0.4055 mL | |
| 25 mM | 0.0130 mL | 0.0649 mL | 0.1298 mL | 0.3244 mL | |
| 30 mM | 0.0108 mL | 0.0541 mL | 0.1081 mL | 0.2704 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
RGLS4326 Related Classifications
HY-139290 Related Classifications
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