| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Tivanisiran sodium targets transient receptor potential vanilloid 1 (TRPV1) mRNA. TRPV1 is a non-selective cation channel expressed on sensory nerve endings in the cornea and ocular surface. It is activated by noxious stimuli such as heat, capsaicin, and inflammatory mediators, and it plays a key role in pain perception and inflammation. Tivanisiran is a synthetic siRNA that binds to TRPV1 mRNA via RNA interference (RNAi), leading to its degradation. This reduces TRPV1 protein levels, thereby reducing pain and inflammation associated with dry eye disease.
|
|---|---|
| ln Vitro |
Tivanisiran sodium is a small interfering RNA (siRNA) that was designed to silence the transient receptor potential vanilloid 1 (TRPV1) mRNA. By silencing TRPV1 expression, it can reduce pain and inflammation. In preclinical studies, tivanisiran effectively reduced TRPV1 expression in corneal cells. No specific IC50 or EC50 values for TRPV1 knockdown are reported. The compound is used for the study of dry eye disease. Tivanisiran is formulated as an ophthalmic solution (eye drops) for topical administration.
|
| ln Vivo |
Tivanisiran sodium has been studied in Phase 3 clinical trials for the treatment of dry eye disease (DED), including DED caused by Sjögren‘s syndrome. In the Phase 3 FYDES safety trial, tivanisiran ophthalmic solution was administered once daily for approximately 360 days and met its primary endpoint (safety). However, in a Phase 3 trial for Sjögren's syndrome-related dry eye, the study missed its primary efficacy endpoint, and the drug did not significantly improve symptoms of dry eye disease. The compound is generally safe and well-tolerated.
|
| Enzyme Assay |
Tivanisiran is an siRNA and does not bind directly to proteins; it binds to TRPV1 mRNA via complementary base pairing. Its activity is measured by its ability to reduce TRPV1 mRNA and protein levels. In vitro potency is assessed by transfecting cells (e.g., HEK293, corneal epithelial cells) with the siRNA using a transfection reagent. After 48-72 hours, TRPV1 mRNA levels are measured by qRT-PCR, and TRPV1 protein levels are measured by Western blot or ELISA. The IC50 or EC50 for mRNA knockdown is determined from dose-response curves (0.1-100 nM). No specific values are reported.
|
| Cell Assay |
For cellular assays, human corneal epithelial cells (HCECs) or TRPV1-expressing cells (e.g., HEK293-TRPV1) are seeded in 6- or 96-well plates. Tivanisiran sodium is delivered using a transfection reagent (e.g., Lipofectamine RNAiMAX) at concentrations of 1-100 nM. After 48-72 hours, cells are harvested. TRPV1 mRNA is quantified by qRT-PCR. TRPV1 protein levels are measured by Western blot. A functional knockdown assay is performed: cells are treated with a TRPV1 agonist (e.g., capsaicin), and Ca2+ influx is measured using Fluo-4 AM. Reduced Ca2+ influx indicates successful knockdown.
|
| Animal Protocol |
For in vivo evaluation of dry eye disease, female BALB/c mice (6-8 weeks old) are used. Dry eye is induced by exposing mice to a desiccating environment (low humidity, high airflow) or by scopolamine injection (to reduce tear production). Tivanisiran sodium is administered topically to the eyes as eye drops (1-10 ug/eye, 1-2 drops, 1-2 times daily) for 7-14 days. Tear production is measured by the phenol red thread test or the Schirmer‘s test. Corneal fluorescein staining is performed to assess corneal epithelial damage. TRPV1 mRNA and protein levels in the cornea are measured by qRT-PCR and Western blot. The number of inflammatory cells in the cornea and conjunctiva is assessed by histology. Pro-inflammatory cytokine levels (IL-1beta, TNF-alpha) in tear fluid or corneal lysates are measured by ELISA. In clinical trials, tivanisiran sodium (1.125% ophthalmic solution) was administered as one drop per eye once daily.
|
| ADME/Pharmacokinetics |
Tivanisiran sodium (C2₆₆H33₈N₆₈Na1₉O14₉P1₉S1₉, MW approx. 6800 Da) is a white to off-white solid powder. For storage, the powder should be kept at -20degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in nuclease-free water or PBS (1-10 mg/mL) can be prepared and stored at -80degC for up to 6 months or at -20degC for 1 month. For topical ophthalmic administration, it is formulated in sterile PBS or an ophthalmic vehicle (e.g., 0.3% sodium hyaluronate). No detailed PK parameters are reported; as a topical siRNA, it acts locally in the cornea with minimal systemic absorption.
|
| Toxicity/Toxicokinetics |
In clinical trials, tivanisiran sodium was generally well-tolerated. The most common adverse events were mild eye irritation (burning, stinging) and eye redness at the application site. In the Phase 3 safety trial, tivanisiran was well-tolerated with a favorable safety profile. No serious treatment-related adverse events were reported. As a research-grade compound, it is not intended for human use in its research form.
|
| References | |
| Additional Infomation |
Tivanisiran sodium (SYL1001) is an investigational siRNA therapeutic for dry eye disease (DED) developed by Sylentis (a PharmaMar group company). Dry eye disease is a common condition affecting millions of people worldwide, characterized by ocular pain, irritation, and blurred vision. TRPV1 is a key mediator of ocular pain and inflammation in DED. Tivanisiran was designed to provide a novel, disease-modifying treatment for DED by targeting the underlying pain pathway rather than simply lubricating the eye. Tivanisiran has been studied in multiple Phase 1, Phase 2, and Phase 3 clinical trials. While it met its safety endpoints, it failed to meet its primary efficacy endpoint in a Phase 3 trial for Sjögren‘s syndrome-associated dry eye. Development may have been discontinued. The compound is for research use only and has not received regulatory approval.
|
| Molecular Formula |
C361H411N141O262NA36P36
|
|---|---|
| Molecular Weight |
12859.67
|
| CAS # |
1848239-71-3
|
| Appearance |
Solid powder
|
| Synonyms |
SYL1001 sodium
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.0778 mL | 0.3888 mL | 0.7776 mL | |
| 5 mM | 0.0156 mL | 0.0778 mL | 0.1555 mL | |
| 10 mM | 0.0078 mL | 0.0389 mL | 0.0778 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
