| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
DHPS[1]; The primary target of GC7 is deoxyhypusine synthase (DHPS/DHS), as well as related enzymes in spermidine synthesis and metabolic pathways. DHPS catalyzes the first step of the conversion of a specific lysine residue (Lys50 in human eIF5A) to the intermediate deoxyhypusine modification, which is the rate-limiting step for eIF5A activation. eIF5A is the only known substrate protein of DHPS in eukaryotic cells, and its hypusination promotes the translation of a subset of mRNAs involved in cytokine responses, cell proliferation, differentiation and stress responses. GC7 competitively inhibits the binding of spermidine to DHPS by specifically interacting with the active site of DHPS, with a Ki value of 9.7 nM. Additionally, GC7 indirectly regulates cell cycle progression through the p21/Cdk4/Rb signaling pathway.
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| ln Vitro |
The treatment of MYCN2 (±Dox) and BE(2)-C cells with GC7 for 72 h at various concentrations (0.1 to 100 μM) significantly reduces the number of viable cells in a dose-dependent manner. In MYCN2 cells, 5 μM of GC7 inhibits cell viability by ~40 and ~60 %, respectively, compare to untreated control cells. BE(2)-C cells require 25 μM of GC7 to reduce cell viability by ~50 %. Exposure to 10 and 100 μM GC7 for 72 h clearly decreases the levels of total retinoblastoma (Rb) and phosphorylated Rb as well as of Cdk4 protein, and increases the levels of p21 protein[1]. Between 0 and 20 μM, GC7 induces little cytotoxicity in HCC cells, while higher concentrations of GC7 (50 to 100 μM) significantly inhibits the viability of all five HCC cell lines tested. Newly synthesized 3H-labeled hypusine of eIF5A1/eIF5A2 is rarely detected after 20 μM GC7 treatment, compare to untreated control. The activity of [3H]-spermidine incorporated into HCC cells is significantly decreased by 20 μM GC7 or higher concentration[2].
GC7 exhibits significant antiproliferative activity against various cell lines in vitro. After 72 hours of treatment in MYCN2 and BE(2)-C neuroblastoma cells, GC7 significantly reduces viable cell numbers in a dose-dependent manner within the concentration range of 0.1 to 100 μM. In MYCN2 cells, 5 μM GC7 reduces cell viability by approximately 40%-60%; whereas the drug-resistant, MYCN-amplified BE(2)-C cell line requires 25 μM to reduce cell viability by approximately 50%. In hepatocellular carcinoma (HCC) cells, between 0 and 20 μM, GC7 induces little cytotoxicity, while higher concentrations (50 to 100 μM) significantly inhibit the viability of all five tested HCC cell lines. Western blot analysis shows that treatment with ≥5 μM GC7 for 72 hours reduces total retinoblastoma protein (Rb), phosphorylated Rb and cyclin-dependent kinase 4 (Cdk4), while increasing the expression of the cell cycle inhibitor p21. The mechanism acts primarily through the p21/Cdk4/Rb signaling axis to induce cell cycle arrest. Additionally, in CHO cells, 1 μM GC7 inhibits hypusine production. |
| ln Vivo |
GC7 demonstrates therapeutic potential in various animal models. In obese diabetic C57BLKS/J-db/db mice, a 2-week treatment with GC7 improved glucose tolerance, increased insulin release, and enhanced β cell mass. In a humanized T1D mouse model, inhibition of eIF5A hypusination by GC7 altered the pancreatic microenvironment by reducing Th1/Th17 response, increasing Treg numbers, decreasing serum IL-17 and IL-21 cytokine levels, reducing anti-GAD65 antibodies, and ablating ER stress to improve β-cell function. In rats, intraperitoneal injection of GC7 substantially reduced renal levels of hypusinated eIF5A and protected against ischemia-reperfusion-induced renal injury. In a Melan-a Tm5 murine melanoma model, administration at a dose of 0.9 mg/kg reduced tumor growth. In a stroke model, a single GC7 pre- or post-treatment significantly reduced infarct volume and improved mouse performance in rotarod and Morris water-maze tests. However, the therapeutic application of GC7 is limited by low selectivity and restricted bioavailability.
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| Enzyme Assay |
The in vitro enzymatic inhibition assay for GC7 is typically performed as follows: Recombinant DHPS enzyme is incubated in a buffer system containing 50 mM HEPES (pH 7.5), 1 mM DTT. Increasing concentrations of GC7 (0.1 nM–100 μM) are added along with spermidine and eIF5A substrate peptides. The reaction is carried out at 37°C for 30-60 minutes. NAD⁺ is added as a cofactor to initiate the reaction. The production of the reaction product deoxyhypusine is quantified by HPLC or radiolabeling detection (³H-spermidine or ¹⁴C-spermidine incorporation assay) to calculate inhibitory activity. The IC₅₀ values of GC7 against mammalian DHPS range from 17-50 nM, with a Ki value of 9.7 nM.
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| Cell Assay |
In vitro cell-based assays typically use neuroblastoma cell lines (such as MYCN2, BE(2)-C, SH-SY5Y) or other relevant tumor cell lines. Cells are cultured in DMEM or RPMI-1640 medium containing 10% fetal bovine serum and 1% penicillin/streptomycin in a 5% CO₂ incubator at 37°C. GC7 powder is first dissolved in sterile water to prepare a stock solution (typically 10-50 mM), then diluted with culture medium to working concentrations (0.1–100 μM). Cells are seeded in 96-well plates (approximately 5 × 10³ cells per well) and cultured overnight before being treated with various concentrations of GC7 for 72 hours. Cell viability is measured using MTS or CCK-8 reagents: MTS reagent is added to each well, incubated at 37°C for 1-4 hours, and absorbance is read at 490 nm or 450 nm. Flow cytometry is used to analyze cell cycle progression and apoptosis. Western blot is performed to detect signaling pathway proteins (such as p21, Rb, p-Rb, Cdk4). Additionally, ³H-spermidine incorporation can be measured to evaluate eIF5A hypusination inhibition.
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| Animal Protocol |
In in vivo experiments, GC7 is typically administered via intraperitoneal injection. Using C57BLKS/J-db/db obese diabetic mice as an example: GC7 is dissolved in sterile saline or PBS and administered at a dose of 1-5 mg/kg/day via intraperitoneal injection for 2 consecutive weeks. Control groups receive an equal volume of vehicle. Body weight and blood glucose levels are monitored weekly during treatment. On day 14, an oral glucose tolerance test (OGTT) or intraperitoneal glucose tolerance test (IPGTT) is performed: after overnight fasting, mice receive a glucose solution (1-2 g/kg body weight), and blood samples are collected at 0, 15, 30, 60, 90, and 120 minutes to measure blood glucose and insulin levels. After euthanasia, pancreatic tissues are isolated for H&E staining and immunohistochemistry analysis to assess changes in β cell mass. For pharmacokinetic evaluation, mice receive a single intraperitoneal injection of GC7 (2 mg/kg), and plasma samples are collected at 0, 0.25, 0.5, 1, 2, 4, 8, and 24 hours; drug concentrations are determined by LC-MS/MS. In the Melan-a Tm5 murine melanoma model, GC7 (0.9 mg/kg) is administered daily via tail vein or intraperitoneal injection for 14-21 days, with tumor volume and body weight measured every 3 days. Additionally, in a renal ischemia-reperfusion injury model, rats receive an intraperitoneal injection of GC7 (8 mg/kg) 30 minutes before surgery, followed by an identical dose after surgery; renal tissues are collected for Western blot analysis of hypusinated eIF5A levels.
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| ADME/Pharmacokinetics |
Previous studies have indicated that the therapeutic application of GC7 is limited by its restricted bioavailability. Due to the polar guanidino group in the molecule, GC7 has low lipophilicity and poor oral bioavailability; intraperitoneal injection is the preferred route of administration in animal experiments (offering superior bioavailability to oral administration). In vitro solubility assays have shown that GC7 has a solubility of ≥12.78 mg/mL in water with ultrasonic assistance, is insoluble in DMSO, and insoluble in ethanol. In in vitro cell experiments, GC7 concentration typically ranges from 0.1-100 μM; in animal models, the commonly used intraperitoneal injection dose ranges from 0.9-5 mg/kg/day. Comprehensive pharmacokinetic parameters (including half-life T₁/₂, clearance Cl, steady-state volume of distribution Vdss, maximum plasma concentration Cmax, time to peak concentration Tmax, and oral bioavailability F%) have not yet been systematically reported. Please refer to the latest literature for specific values.
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| Toxicity/Toxicokinetics |
Toxicological information for GC7 mainly comes from in vitro cytotoxicity assessments and material safety data sheets. In in vitro experiments, between 0-20 μM, GC7 induces little cytotoxicity in HCC cells, while higher concentrations (50-100 μM) significantly inhibit cell viability, indicating concentration-dependent cytotoxicity. Safety data sheets indicate that under fire conditions, the compound may decompose and emit toxic fumes; direct inhalation, eye contact, and skin contact should be avoided. Appropriate exhaust ventilation should be used during handling, and dust and aerosol formation should be avoided. GC7 toxicity classification: irritating to skin, risk of serious damage to eyes, and prolonged exposure may cause serious damage to health. This compound is not intended for human diagnostic or therapeutic use and is limited to basic research use only. It is recommended to operate in a fume hood, wearing protective gloves and goggles, and to store at -20°C in a dry, dark environment. Systematic long-term in vivo toxicology data are currently not available.
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| References |
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| Additional Infomation |
2-(7-Aminoheptyl)guanidine belongs to the guanidine class of compounds, in which the imino hydrogen atom on the guanidine group is replaced by a 7-aminoheptyl group. It is an inhibitor of deoxyxanthine synthase (GO:0034038). It functions as an inhibitor of EC 2.5.1.46 (deoxyxanthine synthase) and as an antitumor drug. It belongs to the guanidine class of compounds and is also a primary amino compound.
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| Molecular Formula |
C8H20N4
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|---|---|
| Molecular Weight |
172.271201133728
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| Exact Mass |
172.169
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| CAS # |
150333-69-0
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| Related CAS # |
150417-90-6
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| PubChem CID |
448393
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.269
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
12
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| Complexity |
118
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| Defined Atom Stereocenter Count |
0
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| SMILES |
NCCCCCCC/N=C(\N)/N
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| InChi Key |
YAOAMZOGXBMLFQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H20N4/c9-6-4-2-1-3-5-7-12-8(10)11/h1-7,9H2,(H4,10,11,12)
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| Chemical Name |
2-(7-aminoheptyl)guanidine
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| Synonyms |
2-(7-aminoheptyl)guanidine; 150333-69-0; N-guanyl-1,7-diaminoheptane; 1,7-Diaminoheptane, N-amidino-; 1-(7-aminoheptyl)guanidine;
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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 | 5.8048 mL | 29.0242 mL | 58.0484 mL | |
| 5 mM | 1.1610 mL | 5.8048 mL | 11.6097 mL | |
| 10 mM | 0.5805 mL | 2.9024 mL | 5.8048 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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