PD: NUCC-390 is a novel, potent, and specific small-molecule CXCR4 receptor agonist. NUCC-390 induces internalization of CXCR4 receptors and acts in an opposite way of AMD3100 . NUCC-390 promotes nerve recovery of function after neurodegeneration in vivo.
Physicochemical Properties
| Molecular Formula | C23H33N5O |
| Molecular Weight | 395.541024923325 |
| Exact Mass | 395.268 |
| CAS # | 1060524-97-1 |
| Related CAS # | NUCC-390 dihydrochloride;2749281-71-6 |
| PubChem CID | 45159110 |
| Appearance | Light brown to brown solid powder |
| LogP | 2.9 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 29 |
| Complexity | 517 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | QUEIKILOAGDRRO-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C23H33N5O/c1-2-14-28-21-7-6-19(25-13-10-18-8-11-24-12-9-18)17-20(21)22(26-28)23(29)27-15-4-3-5-16-27/h8-9,11-12,19,25H,2-7,10,13-17H2,1H3 |
| Chemical Name | Piperidin-1-yl-[1-propyl-5-(2-pyridin-4-ylethylamino)-4,5,6,7-tetrahydroindazol-3-yl]methanone |
| Synonyms | NUCC-390 NUCC 390 NUCC390 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | NUCC-390 (10 μM) causes a significant (Ca)i response, which can be inhibited by AMD3100, a powerful and selective CXCR4 antagonist (1). NUCC-390 (10 μM; 30 min pretreatment) elevates pERK levels, stimulating signaling downstream of the CXCR4 receptor [1]. NUCC-390 (10 μM; 2 hr) promotes CXCR4 receptor internalization. Untreated cells exhibit diffuse expression of CXCR4-YFP throughout the cytoplasm, while HEK cells exhibit unambiguous expression at the cell membrane [1]. NUCC-390 (0-1.25 μM; 24 hours) stimulates axonal development in cultured cerebellar granule neurons (CGN) via CXCR4 [2]. |
| ln Vivo | Following acute nerve terminal injury with α-LTx in CD-1 mice, NUCC-390 (hindlimb injection; 3.2 mg/kg; twice daily; 3 days) aids in the functional and anatomical recovery of the neuromuscular junction (NMJ) [2]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: C8161 Cell Tested Concentrations: 10 μM Incubation Duration: 30 minutes pretreatment Experimental Results: Increased pERK levels. Cell proliferation assay[2] Cell Types: Cerebellar granule neurons (CGN) Tested Concentrations: 0 μM; 0.0625μM; 0.25μM; 1.25 μM Incubation Duration: 24 hrs (hours) Experimental Results: Stimulation of axonal growth by CXCR4. |
| Animal Protocol |
Animal/Disease Models: Six to eightweeks old CD1 mice [2] Doses: 3.2 mg/kg Route of Administration: hindlimb injection; twice (two times) daily; 3 days Experimental Results: Promote functional and anatomical recovery of NMJ. |
| References |
[1]. Discovery and characterization of novel small-molecule CXCR4 receptor agonists and antagonists.Sci Rep. 2016 Jul 26;6:30155. [2]. An Agonist of the CXCR4 Receptor Strongly Promotes Regeneration of Degenerated Motor Axon Terminals.Cells. 2019 Sep 30;8(10). pii: E1183. |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5282 mL | 12.6409 mL | 25.2819 mL | |
| 5 mM | 0.5056 mL | 2.5282 mL | 5.0564 mL | |
| 10 mM | 0.2528 mL | 1.2641 mL | 2.5282 mL |