| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Targets |
SSTR5 antagonist 1 targets somatostatin receptor subtype 5 (SSTR5), a G protein-coupled receptor (GPCR) that mediates the effects of somatostatin. The compound shows high selectivity for SSTR5 over SSTR1-4. At 10 microM, it inhibits SSTR1 by 11%, SSTR2 by 8%, SSTR3 by 14%, and SSTR4 by 10%, demonstrating significant selectivity for SSTR5. The compound is orally bioactive.
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| ln Vitro |
SSTR5 antagonist 1 (compound 25a) reduced hERG activity by 5.6% at 30 μM[1]. The inhibitory effect of SSTR5 antagonist 1 (10 μM) on SSTR5 is higher than that of SSTR1-4, with respective inhibition rates of 11%, 8%, 14%, and 10% [1]. On both human and mouse microsomes, SSTR5 antagonist 1 (1 μM; 15 min and 30 min) shows good metabolic stability, with in vitro CLint values of <10 μL/min/kg (HLM) and 19 μL/min/kg (MLM), respectively [1].
SSTR5 antagonist 1 demonstrates potent in vitro antagonism of SSTR5 with IC50 values of 9.6 nM for hSSTR5 and 57 nM for mSSTR5. It shows high selectivity over other somatostatin receptor subtypes. The compound exhibits good binding affinity and functional antagonism at SSTR5. The compound is orally available. Purity is typically >99%. |
| ln Vivo |
In pharmacokinetic screens, SSTR5 antagonist 1 (compound 25a) (1 mg/kg; oral; single dose) was given orally with good solubility (260 μg/mL, pH= 6.8) and acceptable mouse plasma exposure[1]. In C57BL/6J mice fed a high-fat diet, SSTR5 antagonist 1 (100 mg/kg; oral; single dose; measured 0-120 minutes) lowers blood glucose concentrations and increases insulin secretion in a glucose-dependent manner [1]. In C57BL/6J mice given a high-fat diet, SSTR5 antagonist 1 (1, 3, 10, and 30 mg/kg; oral; single dose) exhibits a dose-dependent effect on glucose excursions as assessed by an oral glucose tolerance test [1]. Male ICR mice (8 weeks old) with respect to pharmacokinetic characteristics [1]: route dose (mg/kg), CLtotal (mL/h/kg), Vss (mL/kg), MRT (h) iv 0.1 1761 3052 1.7 / route Dose (mg/kg) Cmax (ng/mL) Tmax (h) AUC0-8 h (ng·h/mL) F (%) po 1 74.8 2.0 332 58
SSTR5 antagonist 1 demonstrates in vivo activity as an orally bioavailable SSTR5 antagonist. At 30 microM, the compound reduced hERG activity by 5.6%. The inhibitory effect of SSTR5 antagonist 1 (10 microM) on SSTR5 is higher than on SSTR1-4. The compound is designed for oral administration and shows good bioavailability. It is used in studies of SSTR5 physiology and as a potential therapeutic agent. |
| Enzyme Assay |
In vitro receptor binding assays for SSTR5 antagonist 1 typically employ membrane preparations from cells expressing human or mouse SSTR5. Radioligand binding assays using ¹2⁵I-labeled somatostatin or other appropriate radioligands are performed to determine binding affinity (IC50). Competition binding experiments are conducted with varying concentrations of the antagonist. Functional assays measure inhibition of SSTR5-mediated signaling, typically cAMP accumulation or calcium flux, in response to agonist stimulation.
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| Cell Assay |
In vitro cellular assays for SSTR5 antagonist 1 involve treating cells expressing SSTR5 with varying concentrations of the compound (typically 0.001-100 microM range) prior to or concurrently with SSTR5 agonist stimulation. Readouts include measurement of intracellular cAMP levels (decreased by SSTR5 activation), calcium mobilization, or downstream signaling pathway activation. Antagonist potency (IC50) is determined from dose-response curves. Selectivity is assessed using cells expressing SSTR1-4.
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| Animal Protocol |
Animal/Disease Models: C57BL/6J mice fed with high-fat diet [1]
Doses: 100 mg/kg Doses: po (oral gavage); single dose; monitoring over 2 hrs (hrs (hours)) Experimental Results: demonstrated maximum efficacy better than 10 mg/kg glibenclamide and equivalent to 30 mg/kg alogliptin . Increases insulin secretion in a glucose-dependent manner and exhibits hypoglycemic effects, indicating its antidiabetic efficacy in vivo. In vivo animal studies for SSTR5 antagonist 1 typically involve oral administration in rodent models. Pharmacodynamic studies assess SSTR5 antagonism by measuring changes in hormone levels (e.g., growth hormone, insulin) or other biomarkers regulated by SSTR5 signaling. Efficacy studies in appropriate disease models may be performed. The compound's oral bioavailability supports convenient dosing regimens. Dose-ranging studies determine optimal dosing. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of SSTR5 antagonist 1 are characterized by its oral bioavailability. The compound is designed for oral administration with appropriate absorption and exposure profiles. Molecular weight of 511.59 suggests drug-like properties. PK parameters including half-life, Cmax, Tmax, and AUC are determined via LC-MS/MS analysis of plasma samples following oral and intravenous administration. The compound is soluble in DMSO (90 mg/mL).
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| Toxicity/Toxicokinetics |
Toxicological data for SSTR5 antagonist 1 indicates that the compound has a favorable safety profile. At 30 microM, it reduced hERG activity by only 5.6%, suggesting low cardiac liability. As a research compound, standard safety precautions should be observed during handling including appropriate PPE and work in a fume hood. Comprehensive toxicology studies would be required for clinical development. The compound is for research use only.
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| References | |
| Additional Infomation |
SSTR5 antagonist 1 (CAS# 1628741-91-2) is a selective, orally available somatostatin receptor subtype 5 antagonist. It is also known as compound 25a. SSTR5 is involved in regulating hormone secretion, including insulin and growth hormone, making this antagonist a potential therapeutic candidate for metabolic disorders and endocrine diseases. The compound shows high selectivity over other SSTR subtypes. It is typically stored at -20degC.
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| Molecular Formula |
C28H34FN3O5
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| Molecular Weight |
511.585071086884
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| Exact Mass |
511.248
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| CAS # |
1628741-91-2
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| PubChem CID |
90423921
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| Appearance |
White to off-white solid powder
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| LogP |
1.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
37
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| Complexity |
790
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C=CC(=CC=1)C1=C(C=C(C=C1OCC)CN1CC2(CC(=NO2)N2CCC(C(=O)O)CC2)C1)OCC
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| InChi Key |
UQRAIIGEZLINAT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H34FN3O5/c1-3-35-23-13-19(14-24(36-4-2)26(23)20-5-7-22(29)8-6-20)16-31-17-28(18-31)15-25(30-37-28)32-11-9-21(10-12-32)27(33)34/h5-8,13-14,21H,3-4,9-12,15-18H2,1-2H3,(H,33,34)
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| Chemical Name |
1-[2-[[3,5-diethoxy-4-(4-fluorophenyl)phenyl]methyl]-5-oxa-2,6-diazaspiro[3.4]oct-6-en-7-yl]piperidine-4-carboxylic acid
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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) |
DMSO : ~90 mg/mL (~175.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.25 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.25 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.25 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9547 mL | 9.7735 mL | 19.5469 mL | |
| 5 mM | 0.3909 mL | 1.9547 mL | 3.9094 mL | |
| 10 mM | 0.1955 mL | 0.9773 mL | 1.9547 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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