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| Targets |
NIBR-0213 targets S1P1 (sphingosine 1-phosphate receptor 1), a G protein-coupled receptor involved in lymphocyte trafficking and immune regulation. It acts as a competitive antagonist, blocking S1P binding to S1P1. By antagonizing S1P1, NIBR-0213 prevents lymphocyte egress from lymph nodes, reducing immune cell infiltration into target tissues. This mechanism underlies its efficacy in autoimmune disease models. The compound shows high selectivity for S1P1 over other S1P receptors.
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| ln Vitro |
In Ca2+ mobilization tests, NIBR-0213 is inert (IC50 >10 μM) on S1P2, S1P3, and S1P4, but exhibits inhibitory effect on hS1P1 (IC50 of 2.5 nM)[1]. In GTPγ35S tests, NIBR-0213 exhibits strong and similar activity against human and rat S1P1 (IC50 of 2.0 nM and 2.3 nM, respectively), but on mouse S1P1, it has an IC50 of 8.5 nM[1]. In the GTPγ35S test, NIBR-0213 exhibits a selectivity of approximately 3,000 times against human S1P5[1]. The Kd of NIBR-0213, a competitive antagonist of S1P1, is 0.37±0.031 nM [1].
In vitro, NIBR-0213 shows potent antagonist activity at human and rat S1P1 in GTPγ³⁵S assays with IC₅₀ values of 2.0 nM and 2.3 nM, respectively. It blocks S1P1-selective ligand AUY954-induced Ca²⁺ mobilization with IC₅₀ = 2.5 nM in human S1P1-transfected HeLa cells. The compound demonstrates >10 μM IC₅₀ against human S1P5, indicating excellent selectivity. NIBR-0213 is a competitive antagonist that effectively blocks S1P1-mediated signaling. |
| ln Vivo |
When rats are given NIBR-0213 orally at a dose of 30 mg/kg, the peripheral blood lymphocyte (PBL) counts are reduced by 75%–85% after 14 hours, and this effect lasts for 24 hours after treatment[1]. When administered therapeutically, NIBR-0213 (30 mg/kg and 60 mg/kg) is effective in a mouse model of experimental autoimmune encephalomyelitis (EAE)[1]. NIBR-0213 exhibits strong oral bioavailability (69%) and moderate clearance (26 mL/min/kg) in its PK characteristics, which result in substantial exposure following oral dosage[1].
In vivo, NIBR-0213 is effective in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. The compound increases in a dose-dependent manner the leakage of plasma proteins into lung parenchyma. Its oral bioavailability enables convenient administration. NIBR-0213 is a valuable tool for studying S1P1 function in autoimmune diseases. Detailed efficacy data and dosing regimens are available in the primary literature. |
| Enzyme Assay |
In vitro receptor binding and functional assays for NIBR-0213 typically use membrane preparations from cells expressing human or rat S1P1 receptors. GTPγ³⁵S binding assays measure receptor activation: membranes are incubated with GDP, [³⁵S]GTPγS, and varying concentrations of NIBR-0213 in assay buffer (20 mM HEPES, pH 7.4, 100 mM NaCl, 5 mM MgCl₂, 0.1% BSA) at 30°C for 60 minutes. Bound radioactivity is collected by filtration and measured by scintillation counting. For Ca²⁺ mobilization assays, cells loaded with calcium-sensitive dye are treated with agonist AUY954 and antagonist NIBR-0213. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
For cell-based assays, HeLa cells stably transfected with human S1P1 are cultured in DMEM with 10% FBS and selection antibiotics. Cells are seeded in 96-well plates and loaded with calcium-sensitive dye (e.g., Fluo-4) for 30-60 minutes. Cells are treated with NIBR-0213 at various concentrations (0.001-10 μM) for 5-15 minutes, followed by agonist AUY954 addition. Calcium flux is measured using a fluorescence plate reader. IC₅₀ values for antagonist activity are calculated. Cell viability is assessed by standard assays. All treatments include vehicle controls and are performed in triplicate.
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| Animal Protocol |
Animal/Disease Models: Lewis or Wistar rats (220-250 g, males)[1]
Doses: 30 mg/kg Route of Administration: Orally Experimental Results: decreased the PBL counts by 75%-85% within 14 hr and maintained this effect up to 24 hr posttreatment. Animal/Disease Models: C57BL/6 mice bearing EAE model[1] Doses: 30 mg/kg and 60 mg/kg Route of Administration: 30 mg/kg twice per day (BID) for 3 days and then increased to 60 mg/kg BID until the remainder of the experiment. In total, the treatment lasted 26 days Experimental Results: Resulted in a gradual reduction in disease-scores, with a divergence from vehicle controls that became significant after 5 days. In vivo, NIBR-0213 is typically administered orally to rodents at doses of 1-30 mg/kg. For EAE models, compound is dosed daily starting at disease onset or prophylactically. Clinical scoring is performed daily. Lymph node and spleen cellularity are assessed by flow cytometry. Plasma protein leakage into lung parenchyma is measured by Evans Blue dye (EBD) extravasation at 6 hours post-treatment. Blood is collected for pharmacokinetic analysis. Brain and spinal cord tissues are collected for histopathology. All procedures follow institutional animal care guidelines. |
| ADME/Pharmacokinetics |
NIBR-0213 is an orally bioavailable S1P1 antagonist. The compound shows high potency against human and rat S1P1 (IC₅₀ 2.0 nM and 2.3 nM, respectively). It has excellent selectivity over S1P5 (>10 μM). Detailed pharmacokinetic parameters (bioavailability, half-life, Cmax, AUC) are available from preclinical studies. The compound is metabolized by hepatic enzymes. It is designed for research applications in immunology.
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| Toxicity/Toxicokinetics |
Toxicology data for NIBR-0213 are limited in publicly available sources. The compound increases plasma protein leakage into lung parenchyma in a dose-dependent manner, which may indicate vascular permeability effects. At efficacious doses in EAE models, the compound was generally well-tolerated. Standard safety pharmacology studies would be required for therapeutic development. The compound is for research use only and not intended for human therapeutic applications.
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| References | |
| Additional Infomation |
Sphingosine-1-phosphate receptor type 1 antagonist; structure can be found in the first article.
NIBR-0213 is a research-grade S1P1 antagonist for studying autoimmune diseases. Its primary applications include multiple sclerosis research and immunology. The compound is not approved for clinical use and has not entered clinical trials. It is a valuable tool for elucidating the role of S1P1 in lymphocyte trafficking and immune regulation. The compound is commercially available from various chemical suppliers for research purposes only. |
| Molecular Formula |
C27H29CLN2O3
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|---|---|
| Molecular Weight |
464.99
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| Exact Mass |
464.187
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| CAS # |
1233332-14-3
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| PubChem CID |
59393720
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
6.772
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
662
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=CC(=CC(=C1C(=O)N[C@@H](C)C(=O)O)C)C2=CC(=CC=C2)N[C@H](C)C3=CC(=C(C=C3)Cl)C
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| InChi Key |
KYHUARFFBDLROH-MOPGFXCFSA-N
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| InChi Code |
InChI=1S/C27H29ClN2O3/c1-15-11-20(9-10-24(15)28)18(4)29-23-8-6-7-21(14-23)22-12-16(2)25(17(3)13-22)26(31)30-19(5)27(32)33/h6-14,18-19,29H,1-5H3,(H,30,31)(H,32,33)/t18-,19+/m1/s1
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| Chemical Name |
(2S)-2-[[4-[3-[[(1R)-1-(4-chloro-3-methylphenyl)ethyl]amino]phenyl]-2,6-dimethylbenzoyl]amino]propanoic acid
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| Synonyms |
NIBR0213 NIBR 0213 NIBR-0213
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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 | 2.1506 mL | 10.7529 mL | 21.5058 mL | |
| 5 mM | 0.4301 mL | 2.1506 mL | 4.3012 mL | |
| 10 mM | 0.2151 mL | 1.0753 mL | 2.1506 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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