| Size | Price | Stock | Qty |
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| 50mg |
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| Other Sizes |
rac-NBI-74330 is a novel and potent CXCR3 antagonist
| Targets |
CXCR3 chemokine receptor antagonist [1]
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|---|---|
| ln Vitro |
In primary microglial and astroglial cell cultures prepared from neonatal rats, pretreatment with rac-NBI-74330 (100 nM) for 30 minutes prior to LPS (100 ng/ml) stimulation for 24 hours significantly diminished the LPS-induced upregulation of CXCL10 and CXCL11 protein levels in both cell types, as determined by Western blot analysis. [1]
Western blot analysis of primary glial cultures showed that rac-NBI-74330 treatment reduced the level of CXCL10 in LPS-activated microglia. [1] |
| ln Vivo |
In a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve, repeated intrathecal (i.t.) administration of rac-NBI-74330 (10 µg/5 µl; administered 16h and 1h before CCI, then once daily for 7 days) significantly attenuated the development of tactile and thermal hypersensitivity on day 7 post-CCI, as measured by the von Frey and cold plate tests, respectively. [1]
Repeated intrathecal administration of rac-NBI-74330 (same regimen) in CCI rats significantly diminished microglial cell activation (reduced spinal IBA1 protein level) and increased astroglial cell activation (increased spinal GFAP protein level) on day 7 post-CCI. [1] Repeated intrathecal administration of rac-NBI-74330 (same regimen) in CCI rats downregulated the protein levels of its endogenous ligands CXCL4, CXCL9, and CXCL10 in the spinal cord, and decreased CXCL9 protein level in the dorsal root ganglia (DRG) on day 7 post-CCI. Concurrently, it increased the protein levels of CXCR3 and CXCL11 in the spinal cord, and CXCR3 and CXCL4 in the DRG. [1] Both single and repeated intrathecal administration of rac-NBI-74330 (10 µg/5 µl) enhanced the analgesic effectiveness of a single intrathecal dose of morphine (2.5 µg/5 µl) in CCI rats on day 7 post-CCI, but did not enhance the effectiveness of buprenorphine. [1] Repeated intrathecal administration of rac-NBI-74330 (same regimen) in CCI rats significantly increased the protein level of the mu-opioid receptor (MOR) in the spinal cord compared to naive rats on day 7 post-CCI. [1] Single intrathecal administration of rac-NBI-74330 (10 µg/5 µl) to naive mice did not influence baseline nociceptive transmission. [1] |
| Cell Assay |
Primary microglial and astroglial cell cultures were prepared from the cerebral cortex of 1-day-old Wistar rats. Cells were seeded in culture medium in 6-well plates at a density of 1.2x10^6 cells per well for protein analysis. Primary cultures were treated with rac-NBI-74330 at a concentration of 100 nM, 30 minutes before stimulation with LPS (lipopolysaccharide) at 100 ng/ml. The cells were then incubated with LPS for 24 hours. After treatment, cell lysates were collected for Western blot analysis to measure protein levels of chemokines such as CXCL10 and CXCL11. [1]
Immunostaining for IBA1 (microglial marker) and GFAP (astrocyte marker) was used to identify and ensure the purity of the microglial and astroglial populations in the cultures. [1] |
| Animal Protocol |
For neuropathic pain studies in rats, rac-NBI-74330 was dissolved in 100% DMSO. It was administered intrathecally (i.t.) in a volume of 5 µl at a dose of 10 µg/5 µl. The dosing regimen involved a preemptive injection 16 hours and 1 hour before performing the chronic constriction injury (CCI) of the sciatic nerve. Following CCI, rac-NBI-74330 was administered once daily via the intrathecal catheter for 7 consecutive days. Control animals received the vehicle (100% DMSO) according to the same schedule. Behavioural tests (von Frey and cold plate) were performed 120-125 minutes after the last drug administration on day 7 post-CCI. [1]
To assess the effect on opioid effectiveness, on the 7th day post-CCI, rats chronically treated with vehicle or rac-NBI-74330 received a single intrathecal dose of morphine or buprenorphine (2.5 µg/5 µl) 60 minutes after the last rac-NBI-74330 or vehicle injection. Behavioural tests were then repeated. [1] For studies in naive mice, a single intrathecal injection of rac-NBI-74330 (10 µg/5 µl, dissolved in 100% DMSO) was administered, and behavioural tests were conducted afterwards. [1] |
| References | |
| Additional Infomation |
rac-NBI-74330 is a potent and selective CXCR3 antagonist. This study is the first to demonstrate that the CXCR3 receptor antagonist rac-NBI-74330 can alleviate neuropathic pain and enhance the analgesic effect of morphine in rats. [1] Its mechanism of action may involve rac-NBI-74330 inhibiting the activation of microglia in the spinal cord and the release of pro-pain chemokines (CXCL4, CXCL9, CXCL10), while enhancing astrocyte activation. The enhanced analgesic effect of morphine is also associated with the upregulation of spinal cord μ-opioid receptor (MOR) levels. [1] This study hypothesizes that the CXCR3 signaling pathway plays an important role in neuropathic pain, and blocking this pathway is expected to be an effective target for treating neuropathic pain and improving the efficacy of opioids. [1]
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| Molecular Formula |
C32H27F4N5O3
|
|---|---|
| Molecular Weight |
605.59;
|
| Exact Mass |
605.205
|
| CAS # |
473722-68-8
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| Related CAS # |
473722-68-8 (racemate);855527-92-3 (R-isomer);
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| PubChem CID |
10167713
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
752.5±70.0 °C at 760 mmHg
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| Flash Point |
408.9±35.7 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.605
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| LogP |
3.46
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| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
9
|
| Heavy Atom Count |
44
|
| Complexity |
1020
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
FC1C=CC(=CC=1C(F)(F)F)CC(N(CC1C=NC=CC=1)C(C)C1=NC2C(=CC=CN=2)C(N1C1C=CC(=CC=1)OCC)=O)=O
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| InChi Key |
XMRGQUDUVGRCBS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H27F4N5O3/c1-3-44-24-11-9-23(10-12-24)41-30(39-29-25(31(41)43)7-5-15-38-29)20(2)40(19-22-6-4-14-37-18-22)28(42)17-21-8-13-27(33)26(16-21)32(34,35)36/h4-16,18,20H,3,17,19H2,1-2H3
|
| Chemical Name |
N-[1-[3-(4-ethoxyphenyl)-4-oxopyrido[2,3-d]pyrimidin-2-yl]ethyl]-2-[4-fluoro-3-(trifluoromethyl)phenyl]-N-(pyridin-3-ylmethyl)acetamide
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| Synonyms |
rac-NBI-74330 racNBI74330 rac NBI 74330
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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.) |
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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