Home>>Signaling Pathways>> GPCR/G protein>> Cannabinoid Receptor>>(±)-SLV 319

(±)-SLV 319 (Synonyms: (±)-SLV319; (±)-BMS-646256)

Catalog No.GC10907

(±)-SLV 319 ((±)-SLV319) is the racemate of SLV319.

Products are for research use only. Not for human use. We do not sell to patients.

(±)-SLV 319 Chemical Structure

Cas No.: 362519-49-1

Size Price Stock Qty
(±)-SLV 319 5mg
$69.00
Ship Within 7 Days
10mg
$132.00
Ship Within 7 Days
50mg
$492.00
Ship Within 7 Days

Tel:(909) 407-4943 Email: sales@glpbio.com

Customer Reviews

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Animal experiment:

Rats: SLV319, rimonabant and rosiglitazone are suspended in a 10% dimethylacetamide, 10% cremophor, 10% ethanol and 70% water vehicle. Drugs are administered by oral gavage in a volume of 2 mL/kg body weight at 09:00 hours every day. Treatment groups are as follows: (i) Vehicle: ad libitum access to food (vehicle), (ii) Vehicle: restricted access to food (20% less than average food intake of ad libitum vehicle-treated group for the first 3 days of the study, then 10% less than the average food intake of the ad libitum vehicle-treated group for the remainder of the study) (restricted), (iii) Rosiglitazone (4 mg/kg), (iv) Rimonabant (3 mg/kg) (RIM 3 mg/kg), (v) Rimonabant (10 mg/kg) (RIM 10 mg/kg), (vi) (±)-Ibipinabant ((±)-SLV319) (3 mg/kg) (IBI 3 mg/kg) and (vii) Ibipinabant (10 mg/kg) (IBI 10 mg/kg). Rosiglitazone is used as a positive control for its ability to delay β-cell decline, and rimonabant is used as a positive control for CB1 antagonism[3].

References:

[1]. Chorvat RJ, et al. JD-5006 and JD-5037: peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities. Bioorg Med Chem Lett. 2012 Oct 1;22(19):6173-80.
[2]. Lange JH, et al. Synthesis, biological properties, and molecular modeling investigations of novel 3,4-diarylpyrazolines as potent and selective CB(1) cannabinoid receptor antagonists. J Med Chem. 2004 Jan 29;47(3):627-43.
[3]. Rohrbach K, et al. Ibipinabant attenuates β-cell loss in male Zucker diabetic fatty rats independently of its effects on body weight. Diabetes Obes Metab. 2012 Jun;14(6):555-64.

Background

SLV 319 is described here instead of (±)-SLV 319. SLV 319, also called ibipinabant, is a CB1 antagonist with an IC50 value of 22 nM [1, 2].

There are 2 types of cannabinoid receptors (CB1 and CB2). Their endogenous ligands are primarily anandamide and 2-AG. Cannabinoid receptors and their endogenous ligands together are prominent in the control of food intake and energy metabolism. Stimulation of this endocannabinoid system triggers metabolic processes and leads to lipogenesis, weight gain, insulin resistance, dyslipidemias and impaired glucose homeostasis [2].

C2C12 murine myoblasts were model cells. Exposure to increasing concentrations of ibipinabant at the highest concentration tested (100 μM) for 24 hours significantly decreased cell viability to 73 ± 5%. After 48 hours of exposure to the drug at this concentration only 33 ± 4% of cells remained viable. Cellular reactive oxygen species (ROS) generation is an index of mitochondrial function. A more than 2-fold increase in cellular ROS generation could already be observed after 8 hours exposure to ibipinabant at a concentration of 100 μM compared to the vehicle treated C2C12 myoblasts [3].

CB1 receptor occupancy was related to potencies to increase dopamine (DA) and norepinephrine (NE) releases. In the medial prefrontal cortex (mPFC), SLV 319 caused a significant increase in the extracellular DA level at 10 mg/kg. The time course of the effects of SLV 319 and SR141716A at the 10-mg/kg dose appeared to be similar with peak effects at 30 and 180 min. But SLV 319 showed a more pronounced biphasic effect on DA release. SLV319 administration caused significant increases in extracellular concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), metabolites of DA and NE, after the 10-mg/kg dose in rat [4].

References:
[1].  Srivastava BK, Soni R, Joharapurkar A, et al. Bioisosteric replacement of dihydropyrazole of 4S-(-)-3-(4-chlorophenyl)-N-methyl-N’-[(4-chlorophenyl)-
sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-caboxamidine (SLV-319) a potent CB1 receptor antagonist by imidazole and oxazole.  Bioorganic & medicinal chemistry letters, 2008, 18(3): 963-968.
[2].  Chorvat RJ, Berbaum J, Seriacki K, et al. JD-5006 and JD-5037: peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities. Bioorganic & medicinal chemistry letters, 2012, 22(19): 6173-6180.
[3].  Schirris TJJ, Ritschel T, Renkema GH, et al. Mitochondrial ADP/ATP exchange inhibition: a novel off-target mechanism underlying ibipinabant-induced myotoxicity. Scientific reports, 2015, 5.
[4].  Need AB, Davis RJ, Alexander-Chacko JT, et al. The relationship of in vivo central CB1 receptor occupancy to changes in cortical monoamine release and feeding elicited by CB1 receptor antagonists in rats. Psychopharmacology, 2006, 184(1): 26-35.

Chemical Properties

Cas No. 362519-49-1 SDF
Synonyms (±)-SLV319; (±)-BMS-646256
Chemical Name (S,E)-3-(4-chlorophenyl)-N-((4-chlorophenyl)sulfonyl)-N'-methyl-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboximidamide
Canonical SMILES ClC1=CC=C(C=C1)C2=NN(/C(NS(=O)(C(C=C3)=CC=C3Cl)=O)=N\C)C[C@@H]2C4=CC=CC=C4
Formula C23H20Cl2N4O2S M.Wt 487.4
Solubility DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml,Ethanol:PBS (pH 7.2) (1:2): 0.25 mg/ml Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.0517 mL 10.2585 mL 20.517 mL
5 mM 0.4103 mL 2.0517 mL 4.1034 mL
10 mM 0.2052 mL 1.0259 mL 2.0517 mL
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reviews

Review for (±)-SLV 319

Average Rating: 5 ★★★★★ (Based on Reviews and 20 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for (±)-SLV 319

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.