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| 1mg |
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| 10mg |
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| Other Sizes |
| Targets |
Neurotensin receptor (NTR). SR 142948 dihydrochloride acts as a high-affinity antagonist for both neurotensin receptor subtypes. It demonstrates IC50s of 1.19 nM in h-NTR1-CHO cells, 0.32 nM in HT-29 cells, and 3.96 nM in adult rat brain membranes. The compound recognizes the two binding sites described for the NT receptor.
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| ln Vitro |
SR 142948 (90 minutes; 1 µM) In CHO-hNT1-R cells, dihydrochloride suppresses the expression of c-fos and krox24 [1]. With IC50s of 1.19 and 0.32 nM, respectively, SR 142948 (0-1 µM; 1 hour) dihydrochloride demonstrates good antagonistic activity by preventing the binding of [125I-Tyr3]NT to h-NTR1-CHO and HT 29 cell membranes [2]. In h-NTR1-CHO and HT 29 cells, SR 142948 (0-1 µM; 30 min) dihydrochloride antagonistically inhibits NT-stimulated IP1 synthesis in a concentration-dependent manner [2]. In h-NTR1-CHO cells, SR 142948 (1, 10 nM; 60-80 sec) dihydrochloride inhibits NT-stimulated intracellular calcium mobilization [2].
In vitro, SR 142948 dihydrochloride potently antagonizes NT-induced inositol monophosphate formation in HT-29 cells (IC50 = 3.9 nM) and inhibits NT-induced intracellular calcium mobilization in CHO cells expressing the human receptor. At an i.p. dose of 0.1 mg/kg, it completely antagonizes NT-evoked acetylcholine release in the rat striatum. |
| ln Vivo |
SR 142948 (oral, single-dose, 2 µg/kg) Turning behavior elicited by NT (10 pg/mouse) is inhibited by dihydrochloride [2]. SR 142948 (i.p.; single dose; 0.01–0.03, 0.3 mg/kg) In a dose-dependent manner, dihydrochloride inhibits the increased ACh release generated by NT (100 nM) [2]. NT-induced hypothermia is slightly but significantly blocked by SR 142948 (90–10 mg/kg; PO; single dose) dihydrochloride (53% in rats at 2 mg/kg and 54% in mice at 4 mg/kg) [ 2].
In vivo, SR 142948 dihydrochloride dose-dependently inhibits turning behavior induced by unilateral intrastriatal injection of NT in mice at an oral dose range of 0.04-640 × 10^{-3} mg/kg. In contrast to some earlier antagonists, it also blocks both hypothermia and analgesia induced by i.c.v. injection of NT in mice and rats, demonstrating a superior in vivo antagonistic profile and good brain access. |
| Enzyme Assay |
Membrane preparations from h-NTR1-CHO cells, HT-29 cells, or adult rat brain are prepared. [3H]NT (1 nM) or [¹2⁵I-Tyr3]NT is incubated with increasing concentrations of SR 142948 (0-1000 nM) in binding buffer (50 mM Tris-HCl, pH 7.4, 5 mM MgCl2, 0.1% BSA) for 60 min at 25degC. Non-specific binding is determined with 1 uM unlabeled NT. Bound radioactivity is separated by filtration through GF/C filters, and IC₅0 values are calculated via non-linear regression.
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| Cell Assay |
HT-29 cells are pre-incubated with 10 mM LiCl for 30 min. Then, SR 142948 dihydrochloride (1-100 nM) is added with or without 100 nM NT for an additional 30 min. The reaction is terminated by adding perchloric acid. The total inositol monophosphate (IP1) is extracted by ion-exchange chromatography and quantified using a [3H]inositol assay. The IC₅0 for antagonizing NT-induced IP1 accumulation is calculated from a dose-response curve.
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| Animal Protocol |
Animal/Disease Models: Female Swiss albino CD1 mice (25-30 g; intrastriatal injection of 10 pg/mouse NT)[2]
Doses: 2 µg/kg Route of Administration: Oral administration; single Experimental Results: Inhibited the turning behavior with maximal and significant antagonism between 1-2 h after administration. Behavioral testing in male Swiss albino CD1 mice: Mice are injected intrastriatally with NT (2 ug). Turning behavior is recorded 2 min later for 5 min. SR 142948 dihydrochloride is administered orally (0.04-640 × 10^{-3} mg/kg) 1-2 h before the NT injection. The number of turns is counted. A compound is considered an antagonist if it significantly and dose-dependently reduces the number of turns. For hypothermia studies, body temperature is measured using a rectal probe. |
| ADME/Pharmacokinetics |
SR 142948 dihydrochloride is orally bioavailable and has a long duration of action in vivo. After oral administration in mice, it shows a dose-dependent inhibition of NT-induced turning behavior. The compound exhibits good brain access, enabling it to block centrally mediated effects like hypothermia and analgesia. It has a plasma half-life suitable for in vivo pharmacological studies, with effects observed up to 2-4 hours post-administration.
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| Toxicity/Toxicokinetics |
SR 142948 dihydrochloride is used for research only and not for human use. At therapeutic doses, it shows no intrinsic agonist activity, and its pharmacological profile is clean, with effects specific to NT receptor antagonism. However, as with any CNS-active compound, potential off-target effects at high concentrations cannot be excluded. Standard safety precautions for handling research chemicals should be followed.
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| References |
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| Additional Infomation |
SR 142948 dihydrochloride is a research compound that has not entered clinical trials or received regulatory approval for human use. It is a second-generation neurotensin antagonist with a superior pharmacological profile compared to the first antagonist SR 48692. This tool compound is widely used to study the role of neurotensin in psychiatric disorders, pain, and neurodegeneration. It should be stored as a powder at -20degC for long-term stability.
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| Molecular Formula |
C39H53CL2N5O6
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| Molecular Weight |
758.77
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| Related CAS # |
SR 142948;184162-64-9
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| Appearance |
White to off-white solid powder
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3179 mL | 6.5896 mL | 13.1792 mL | |
| 5 mM | 0.2636 mL | 1.3179 mL | 2.6358 mL | |
| 10 mM | 0.1318 mL | 0.6590 mL | 1.3179 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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