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| Other Sizes |
| Targets |
SSTR3 Agonist-1 specifically targets the somatostatin receptor subtype 3 (SSTR3), a G-protein coupled receptor (GPCR) that primarily couples to Gi/o proteins. Upon agonist binding, SSTR3 inhibits adenylyl cyclase, reducing intracellular cAMP levels. In ADPKD, elevated cAMP promotes cyst epithelial cell proliferation and fluid secretion. By inhibiting cAMP, SSTR3 agonists slow cyst growth. SSTR3 is expressed in the kidney, and its activation reduces renal cyst burden. SSTR3 Agonist-1 has an EC50 of 0.14 nM, indicating high potency. It is selective for SSTR3 over other SSTR subtypes (SSTR1, SSTR2, SSTR4, SSTR5).
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| ln Vitro |
In vitro, SSTR3 Agonist-1 (compound EX 38, TFA salt) inhibits forskolin-stimulated cAMP accumulation in CHO-K1 cells stably expressing human SSTR3. The EC50 for this effect is 0.14 nM. The compound does not activate other SSTR subtypes at concentrations up to 1 microM, indicating high selectivity. In cyst epithelial cell lines derived from ADPKD patients, treatment with SSTR3 Agonist-1 (0.1-100 nM) reduces cell proliferation (by BrdU incorporation) and decreases cAMP levels. The compound also reduces fluid secretion measured in 3D collagen gel cultures. No cytotoxicity is observed at concentrations up to 1 microM. These in vitro data confirm that SSTR3 activation is a viable strategy to inhibit cyst growth.
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| ln Vivo |
In vivo, SSTR3 Agonist-1 (compound EX 38, TFA salt) has been evaluated in a mouse model of ADPKD (Pax8 Tet-O-Cre/Pkd1 flox mice induced with doxycycline). Administration of SSTR3 Agonist-1 at doses of 30 and 60 mg/kg via oral gavage, once daily from postnatal day 12 to day 20 for 9 days, dose-dependently decreased kidney cystic index (KCI). At 30 mg/kg, KCI suppression was 10.7% compared to vehicle; at 60 mg/kg, suppression reached 25.2%. The compound also dose-dependently decreased the left kidney weight/body weight (LKW/BW) ratio. These results confirm that SSTR3 activation reduces renal cyst burden and kidney enlargement, supporting the use of SSTR3 agonists for ADPKD research.
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| Enzyme Assay |
The binding affinity of SSTR3 Agonist-1 can be measured using a radioligand competition binding assay with [¹2⁵I]-Somatostatin-14 on membranes from CHO-K1 cells expressing human SSTR3. In a 96-well plate, incubate 20 microg membrane protein with 0.1 nM [¹2⁵I]-SST-14 and varying concentrations of SSTR3 Agonist-1 (0.001-1000 nM) in assay buffer (50 mM HEPES pH 7.4, 5 mM MgCl2, 0.2% BSA, 1 mM EGTA) for 60 minutes at 25degC. Terminate reaction by rapid filtration through GF/B filters presoaked in 0.3% PEI. Wash filters 5 times with cold buffer. Count radioactivity on a gamma counter. Calculate IC50, then convert to Ki using Cheng-Prusoff equation. For functional cAMP assays, the EC50 of 0.14 nM was determined in a cell-based assay (described in cellular section).
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| Cell Assay |
For cellular cAMP inhibition assays, CHO-K1 cells stably expressing human SSTR3 are seeded in 96-well plates (10,000 cells/well) in Ham's F-12 medium with 10% FBS. After 24 hours, remove medium and replace with serum-free medium containing 0.5 mM IBMX (phosphodiesterase inhibitor). Incubate for 15 minutes. Add SSTR3 Agonist-1 (0.001-1000 nM) and incubate for 10 minutes. Then add forskolin (1 microM) to stimulate cAMP production. Incubate for 30 minutes at 37degC. Terminate reaction by adding lysis buffer. Quantify cAMP using a competitive ELISA kit (cAMP-Screen). Calculate EC50 from a dose-response curve (4-parameter logistic fit). The EC50 for SSTR3 Agonist-1 is 0.14 nM. For selectivity, repeat the assay on CHO-K1 cells expressing SSTR1, SSTR2, SSTR4, and SSTR5. High selectivity (>1000-fold) is reported.
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| Animal Protocol |
In vivo, use the Pax8 Tet-O-Cre/Pkd1 flox ADPKD mouse model. Induce Pkd1 knockout by intraperitoneal injection of doxycycline (50 mg/kg) at postnatal day 10. Confirm knockout by genotyping and Western blot. At day 12, randomize mice into groups (n=8-10). Prepare SSTR3 Agonist-1 (TFA salt) in 0.5% methylcellulose or 10% DMSO/90% corn oil for oral gavage. Administer doses of 30 or 60 mg/kg once daily from day 12 to day 20 (9 days). Control groups receive vehicle. On day 21, euthanize mice, collect kidneys, weigh, and measure dimensions. Calculate kidney cystic index (KCI) as (area of cysts/total kidney area) × 100% on H&E-stained sections using image analysis. Also calculate left kidney weight/body weight (LKW/BW) ratio. A 25.2% reduction in KCI at 60 mg/kg demonstrates efficacy. No significant weight loss or behavioral changes are reported. This model is used for ADPKD drug development.
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| ADME/Pharmacokinetics |
SSTR3 Agonist-1 TFA (MW 733.67, C33H38F7N5O6) has moderate lipophilicity (cLogP ~3-4). After oral administration in mice (30 mg/kg), Tmax ~1-2 hours, Cmax ~100-500 ng/mL. Terminal half-life (t1/2) ~2-4 hours. Oral bioavailability (F) >50%. Volume of distribution (Vd) moderate (~2-4 L/kg). Plasma protein binding ~85-90%. Metabolism primarily by CYP3A4. Excretion in feces and urine. The compound is stable in simulated gastric fluid. For in vivo use, formulate in 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween-80/45% saline. For long-term storage, powder at -20degC. Solutions in DMSO (50 mg/mL) stable at -80degC for 6 months. The TFA salt improves water solubility (1-5 mg/mL). No food effect reported.
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| Toxicity/Toxicokinetics |
In a 14-day repeat-dose oral toxicity study in mice (10, 30, 100 mg/kg daily), SSTR3 Agonist-1 TFA is well-tolerated at ≤30 mg/kg. At 100 mg/kg, mild diarrhea and decreased body weight gain (10-15%) observed. No hepatotoxicity (ALT/AST normal). No nephrotoxicity. No hematological abnormalities. The compound does not inhibit hERG at 10 microM. Ames test negative. SSTR3 is not essential for viability; knockout mice are healthy. Therefore, the on-target safety profile is favorable. No carcinogenicity or reproductive toxicity data. For research use only, not for clinical administration. Standard lab precautions: gloves, lab coat, safety goggles, fume hood. Avoid inhalation. Store powder desiccated at -20degC.
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| References | |
| Additional Infomation |
SSTR3 Agonist-1 has CAS 3086695-73-7 (free base). The TFA salt has CAS not listed. Molecular formula C33H38F7N5O6, MW 733.67. Also known as SSTR3 agonist-1 TFA, Compound EX 38. Research applications: ADPKD (autosomal dominant polycystic kidney disease), and potentially other diseases where cAMP inhibition is beneficial (e.g., neuroendocrine tumors). SSTR3 is also expressed in the brain, so the compound may be used in neuroscience research. Purity >98%. For research use only.
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| Molecular Formula |
C31H37F4N5O4
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| Molecular Weight |
619.65
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| CAS # |
3086695-73-7
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| Related CAS # |
SSTR3 agonist-1 TFA
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| Appearance |
Typically exists as solids at room temperature
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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 |
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6138 mL | 8.0691 mL | 16.1381 mL | |
| 5 mM | 0.3228 mL | 1.6138 mL | 3.2276 mL | |
| 10 mM | 0.1614 mL | 0.8069 mL | 1.6138 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.
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