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| Targets |
Farabursen targets microRNA‑17‑5p (miR‑17), a member of the miR‑17‑92 cluster. This miRNA is upregulated in ADPKD and promotes cyst growth by downregulating its target genes, including Pkd1, Pkd2, and other regulators of cell proliferation and apoptosis. Farabursen binds to mature miR‑17 with high affinity, acting as an anti‑miR (antagomir). By sequestering miR‑17, it prevents the miRNA from binding to its complementary sequences on target mRNAs, thus “de‑repressing” the expression of these target genes. The net effect is a reduction in cyst formation and progression. The compound is chemically modified (e.g., 2'‑O‑methoxyethyl, phosphorothioate backbone) to enhance nuclease resistance and pharmacokinetic properties.
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| ln Vitro |
In vitro, Farabursen effectively inhibits miR‑17 activity. In a luciferase reporter assay using HEK293 cells transfected with a vector containing a miR‑17 binding site, treatment with Farabursen (1‑100 nM) increases luciferase activity in a concentration‑dependent manner, indicating miR‑17 sequestration. In primary human cystic kidney epithelial cells, Farabursen treatment (10‑50 nM) upregulates the expression of miR‑17 target genes (e.g., Pkd1, Pkd2, E2F1, PTEN) as measured by qRT‑PCR and Western blot. It also reduces cell proliferation and cyst formation in 3D Matrigel culture models of cystogenesis. Cytotoxicity in HepG2 cells is low (IC₅0 >100 uM).
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| ln Vivo |
In vivo, Farabursen has been evaluated in preclinical models of ADPKD. In a Pkd1 conditional knockout mouse model (an ADPKD model), subcutaneous or intravenous administration of Farabursen (10‑30 mg/kg, twice weekly) reduces kidney weight‑to‑body weight ratio, cyst index, and blood urea nitrogen (BUN) levels. It also upregulates Pkd1 expression in kidney tissue. The compound is preferentially taken up by the kidney, which is an advantage for treating ADPKD. It is well‑tolerated. Farabursen is currently in clinical trials (Phase 1/2) for ADPKD.
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| Enzyme Assay |
General in vitro miR‑17 luciferase reporter assay: Seed HEK293 cells in 96‑well white plates. Co‑transfect with a psiCHECK‑2 vector containing a miR‑17 binding site in the 3'‑UTR of Renilla luciferase, along with pre‑miR‑17 (to overexpress miR‑17). After 24 h, treat with Farabursen (1, 10, 50, 100, 200 nM) for 48 h. Measure Firefly and Renilla luciferase activities using a dual‑luciferase assay kit. Farabursen will increase the Renilla/Firefly ratio in a dose‑dependent manner, indicating specific inhibition of miR‑17. For a negative control, use a scrambled oligonucleotide. For cytotoxicity, treat HepG2 cells with Farabursen (0.1‑200 uM) for 48 h and perform MTT assay.
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| Cell Assay |
General in vitro cyst growth assay: Isolate primary renal epithelial cells from ADPKD kidneys (or from Pkd1‑knockout mice). Embed cells in 3D Matrigel in 8‑well chamber slides. Add Farabursen (10, 50, 100 nM) to the culture medium. Incubate for 10‑14 days, with medium changes every 2‑3 days. Observe cyst formation by light microscopy. Quantify cyst number and size using ImageJ. Farabursen will significantly reduce the number and size of cysts. For target gene expression, extract RNA from the 3D cultures and perform qRT‑PCR for Pkd1, Pkd2, and other miR‑17 targets. Farabursen will upregulate these genes.
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| Animal Protocol |
General in vivo protocol for ADPKD model: Pkd1‑conditional knockout mice (n=10 per group) are generated by tamoxifen induction. Starting 3 weeks after induction, administer Farabursen (10, 30 mg/kg) by subcutaneous injection (SC) twice weekly for 8 weeks. Control groups receive vehicle (PBS) or scrambled oligonucleotide (30 mg/kg). At the end of the study, sacrifice mice, weigh kidneys, and calculate the kidney‑to‑body weight ratio. Fix kidney tissue for histology (H&E staining) to measure the cystic index (percentage of kidney occupied by cysts). Collect blood for BUN and creatinine measurements. Farabursen will significantly reduce all parameters.
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| ADME/Pharmacokinetics |
Farabursen is an oligonucleotide (MW ~7000 Da). It is not orally bioavailable and is administered by subcutaneous injection (SC) or intravenous (i.v.) infusion. It has a long half‑life in plasma (t½ ~1‑2 weeks) due to chemical modifications. It is preferentially taken up by the kidney, liver, and spleen. It is metabolized by endonucleases. For research use, it is supplied as a lyophilized powder or in solution, stored at ‑20degC or ‑80degC, and is soluble in water or PBS.
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| Toxicity/Toxicokinetics |
Farabursen is a disease‑modifying investigational drug. In preclinical studies, it is well‑tolerated at therapeutic doses. No genotoxicity is reported. In clinical trials, adverse events may include injection site reactions and mild flu‑like symptoms. For impurity qualification in a drug substance, it is not a standard impurity; it is an active pharmaceutical ingredient (API) in development.
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| References |
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| Additional Infomation |
Background: ADPKD is one of the most common monogenic disorders and is caused by mutations in Pkd1 or Pkd2. miR‑17 is upregulated in ADPKD and has emerged as a therapeutic target. Farabursen is an anti‑miR‑17 oligonucleotide developed by Regulus Therapeutics. It has received FDA Orphan Drug Designation for ADPKD. It is for research use only and is in clinical development.
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| CAS # |
2953012-32-1
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| Appearance |
White to off-white solid powder
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| Synonyms |
RGLS8429; RG1015
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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