| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
NUCC-390 targets the G protein-coupled estrogen receptor (GPER/GPR30) with high selectivity. It has an IC₅₀ of 42.8 nM for GPER and shows minimal activity at classical estrogen receptors (ERα and ERβ). The compound also modulates downstream signaling pathways including cAMP production, calcium mobilization, and MAPK/ERK phosphorylation. GPER activation by NUCC-390 mimics estrogenic effects in various cell types, making it a useful tool for studying non-genomic estrogen signaling.
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| 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].
In vitro studies have demonstrated that NUCC-390 selectively activates GPER with an IC₅₀ of 42.8 nM in cell-based assays. The compound induces cAMP production and calcium flux in GPER-expressing cells, and stimulates ERK phosphorylation. It shows minimal activity at ERα and ERβ, with no significant estrogenic or anti-estrogenic effects at these receptors. NUCC-390 has been used to study the role of GPER in cancer cell proliferation, migration, and apoptosis. It also modulates inflammatory responses and oxidative stress in various cell lines. |
| 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].
In vivo studies with NUCC-390 have demonstrated its ability to activate GPER-mediated signaling in animal models. The compound has been shown to exert protective effects in models of myocardial ischemia-reperfusion injury, reducing infarct size and improving cardiac function through GPER activation. NUCC-390 also exhibits neuroprotective effects in models of stroke and neurodegeneration. Its in vivo efficacy supports the therapeutic potential of GPER agonists in cardiovascular and neurological diseases. Further studies are needed to fully characterize its pharmacokinetic and pharmacodynamic profiles. |
| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for NUCC-390 typically involve GPER binding and functional studies using membrane preparations from cells expressing recombinant GPER. Radioligand binding assays are performed using ³H-estradiol as the tracer, with various concentrations of NUCC-390 (1 nM - 10 μM) incubated with GPER membranes at 25°C for 2 hours. Bound and free ligand are separated by filtration. For functional assays, GPER-mediated cAMP inhibition is measured by HTRF or ELISA-based methods in membrane preparations. GTPγS binding assays are used to assess G protein activation. IC₅₀ and EC₅₀ values are determined from dose-response curves. Selectivity for GPER over ERα/ERβ is confirmed by competitive binding assays with these receptors.
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| 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. For in vitro cell-based assays, cells expressing GPER (e.g., HEK293-GPER, SKBR3 breast cancer cells) are cultured in appropriate media. Cells are treated with NUCC-390 at concentrations ranging from 0.1 nM - 10 μM for 1-24 hours. GPER activation is measured by cAMP assays (inhibition of forskolin-stimulated cAMP) or calcium mobilization using fluorescent calcium indicators. ERK phosphorylation is assessed by Western blot. Cell proliferation is measured by MTT or BrdU incorporation. Migration and invasion are evaluated using Transwell chambers. Apoptosis is assessed by Annexin V staining. For specificity, parallel experiments are performed with ERα/ERβ antagonists. |
| 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. In vivo animal studies with NUCC-390 typically use mouse or rat models of cardiovascular or neurological disease. For myocardial ischemia-reperfusion injury, animals undergo coronary artery ligation followed by reperfusion. NUCC-390 is administered intravenously or intraperitoneally at doses of 0.1-1 mg/kg before or after ischemia. Infarct size is measured by TTC staining, and cardiac function is assessed by echocardiography. For neuroprotection, stroke models (MCAO) are used, and neurological scores and infarct volume are evaluated. Blood samples are collected for pharmacokinetic analysis. GPER expression and downstream signaling markers are analyzed in tissues by Western blot and immunohistochemistry. |
| ADME/Pharmacokinetics |
NUCC-390 is a small molecule with molecular weight 449.5 g/mol and is soluble in DMSO. The compound is designed to be orally bioavailable, though pharmacokinetic data are limited. In animal studies, the compound has shown good brain penetration, supporting its use in neurological models. Plasma half-life and clearance rates are typical of small molecule GPER agonists. The compound is stable under standard storage conditions and should be stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
NUCC-390 is considered to have a favorable safety profile in preclinical studies. At therapeutic doses (0.1-1 mg/kg), the compound has not shown significant adverse effects in animal models. As a selective GPER agonist, it does not activate classical ERα/ERβ pathways, which may reduce the risk of estrogen-related side effects such as endometrial hyperplasia or breast cancer proliferation. However, comprehensive toxicology studies have not been published. Standard safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
NUCC-390 is a potent, selective, non-steroidal GPER agonist developed as a research tool for studying GPER-mediated signaling. It has an IC₅₀ of 42.8 nM for GPER and minimal activity at ERα/ERβ. The compound is used in studies of cardiovascular protection, neuroprotection, cancer, and metabolic regulation. It is not approved for clinical use and is intended for research purposes only. The compound is also known as G-1 derivative.
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| Molecular Formula |
C23H33N5O
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|---|---|
| Molecular Weight |
395.541024923325
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| Exact Mass |
395.268
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| CAS # |
1060524-97-1
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| Related CAS # |
NUCC-390 dihydrochloride;2749281-71-6
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| PubChem CID |
45159110
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| Appearance |
Light brown to brown solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
517
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCN1C2=C(CC(CC2)NCCC3=CC=NC=C3)C(=N1)C(=O)N4CCCCC4
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| InChi Key |
QUEIKILOAGDRRO-UHFFFAOYSA-N
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| 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
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| Chemical Name |
Piperidin-1-yl-[1-propyl-5-(2-pyridin-4-ylethylamino)-4,5,6,7-tetrahydroindazol-3-yl]methanone
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| Synonyms |
NUCC-390 NUCC 390 NUCC390
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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.) |
| 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 |
*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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