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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Targets |
K-7174-2HCl targets the proteasome and GATA transcription factors. It is a proteasome inhibitor that induces apoptosis. It also inhibits GATA-mediated gene expression, which contributes to its effects on cell adhesion and inflammation. By inhibiting VCAM-1 expression, K-7174-2HCl modulates leukocyte adhesion and inflammatory responses.
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| ln Vitro |
VCAM-1 and its ligands' ability to adhere is inhibited by K-7174 diHClide (10 μM; 1 h) [1]. With an IC50 value of 14 μM, K-7174 diHClide (1-30 μM; 1 h) dose-dependently suppresses VCAM-1 expression [1]. With an IC50 value of 9 μM, K-7174 diHClide (1-30 μM; 1 h) dose-dependently suppresses TNFα activation of VCAM-1 mRNA[1]. In Hep3B cells, K-7174 diHClide (10–20 μM; 24 hours) dose-dependently restores Epo synthesis [2]. K-7174 diHClide decreases GATA binding activity at 2.5–30 μM for 24 hours [2]. K-7174 diHClide (0-25 μM; 72 h) causes apoptosis and suppresses the proliferation of MM cells [3].
In vitro, K-7174-2HCl inhibits cell adhesion and the expression of VCAM-1 induced by IL-1β or TNF-α. As a proteasome inhibitor, it induces apoptosis in various cell types. The compound's ability to inhibit both the proteasome and GATA transcription factors contributes to its pleiotropic effects. Specific in vitro data, including IC50 values, are not extensively provided. |
| ln Vivo |
K-7174 diHClide (30 mg/kg; intraperitoneally once daily for 9 days) reverses hemoglobin concentration and reticulocyte count reductions caused by TNF-α or IL-1β [2]. In vivo tumor growth is inhibited by K-7174 dihydrochloride (75 mg/kg; intraperitoneally administered once daily for 14 days) [3]. K-7174 dihydrochloride is more effective than intraperitoneal injection at inhibiting tumor growth in vivo when taken orally once daily for 14 days at a dose of 50 mg/kg [3].
In vivo, K-7174-2HCl is orally active. It inhibits neuronal degeneration and has antitumor activity. The compound has been studied for its potential in neuropsychiatric systemic lupus erythematosus and cognitive dysfunction. Its ability to inhibit VCAM-1 expression and cell adhesion suggests potential for treating inflammatory and autoimmune diseases. |
| Enzyme Assay |
In vitro enzyme assays for K-7174-2HCl involve measuring proteasome activity and GATA transcription factor binding. Proteasome activity is measured using fluorogenic substrates that are cleaved by the proteasome. GATA binding is assessed using electrophoretic mobility shift assays (EMSA) or chromatin immunoprecipitation (ChIP) assays. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
Cell Viability Assay[3]
Cell Types: KMS12-BM, U266 and RPMI8226 Cell line Tested Concentrations: 0-25 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of MM cell growth. Apoptosis analysis [3] Cell Types: KMS12-BM, U266 and RPMI8226 Cell line Tested Concentrations: 10 μM Incubation Duration: 48 h Experimental Results: As the percentage of annexin-V positive cells increased, the apoptosis of MM cells increased Dramatically. For in vitro cell-based assays, endothelial cells or other cell types are cultured and stimulated with IL-1β or TNF-α in the presence of K-7174-2HCl at various concentrations. VCAM-1 expression is measured by ELISA, flow cytometry, or Western blot. Cell adhesion is assessed using adhesion assays. Apoptosis is measured by Annexin V/PI staining or caspase activity assays. Cell viability is assessed using MTT or similar assays. |
| Animal Protocol |
Animal/Disease Models: ICR mice injected with IL-β or TNF-α [2]
Doses: 30 mg/kg Route of Administration: intraperitoneal (ip) injection; 30 mg/kg, one time/day for 9 days Experimental Results: Erythropoietin (Epo ) yield, reticulocyte count, and hemoglobin (Hb) concentration increased. Animal/Disease Models: NOD/SCID mouse xenograft [3] Doses: 75 mg/kg Route of Administration: intraperitoneal (ip) injection; one time/day for 14 days. Experimental Results: Tumor volume was Dramatically diminished, but body weight was Dramatically diminished after 10 days. Animal/Disease Models: NOD/SCID (severe combined immunodeficient) mouse with murine xenografts [3] Doses: 50 mg/kg Route of Administration: po (oral gavage); one time/day for 14 days Experimental Results: Demonstrated anti-myeloma activity. Oral administration is more effective than intraperitoneal (ip) injection. In vivo animal studies for K-7174-2HCl would typically use mouse models of inflammation, autoimmune disease, or cancer. The compound is administered orally at doses determined from pharmacokinetic studies. Inflammatory markers (e.g., VCAM-1, cytokines) are measured in plasma or tissues. Tumor growth is monitored in xenograft models. Neurological function is assessed in models of cognitive dysfunction or neurodegeneration. |
| ADME/Pharmacokinetics |
K-7174-2HCl has a molecular formula of C33H50Cl2N2O6 and a molecular weight of 641.67. It is an orally active small molecule. It should be stored as a powder at -20°C for up to 3 years or in solution at -20°C for up to 6 months. Detailed pharmacokinetic parameters are not extensively characterized.
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| Toxicity/Toxicokinetics |
Specific toxicity data for K-7174-2HCl are not extensively provided in the available literature. As a proteasome inhibitor, it would be expected to have a safety profile related to proteasome inhibition. The compound is for research use only and is not for human or clinical use. Standard toxicology assessments would be required for therapeutic development.
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| References |
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| Additional Infomation |
K-7174-2HCl is an orally active proteasome and GATA inhibitor. It inhibits cell adhesion and the expression of VCAM-1 induced by IL-1β or TNF-α. It inhibits neuronal degeneration, induces apoptosis, and has antitumor activity. The compound has been studied for its potential in neuropsychiatric systemic lupus erythematosus and cognitive dysfunction. No approved therapeutic status is reported.
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| Molecular Formula |
C33H50CL2N2O6
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| Molecular Weight |
641.6659
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| Exact Mass |
568.351
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| CAS # |
191089-60-8
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| Related CAS # |
K-7174;191089-59-5
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| PubChem CID |
9874191
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| Appearance |
White to yellow solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
689.9±55.0 °C at 760 mmHg
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| Flash Point |
171.2±28.7 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.552
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| LogP |
5.61
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
41
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| Complexity |
663
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC(=CC(=C1OC)OC)/C=C/CCCN2CCN(CCC2)CCC/C=C/C3=CC(=C(C(=C3)OC)OC)OC
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| InChi Key |
JXXCDAKRSXICGM-AOEKMSOUSA-N
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| InChi Code |
InChI=1S/C33H48N2O6/c1-36-28-22-26(23-29(37-2)32(28)40-5)14-9-7-11-16-34-18-13-19-35(21-20-34)17-12-8-10-15-27-24-30(38-3)33(41-6)31(25-27)39-4/h9-10,14-15,22-25H,7-8,11-13,16-21H2,1-6H3/b14-9+,15-10+
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| Chemical Name |
1,4-bis[(E)-5-(3,4,5-trimethoxyphenyl)pent-4-enyl]-1,4-diazepane
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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) |
H2O : ~15 mg/mL (~23.38 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (15.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5584 mL | 7.7922 mL | 15.5843 mL | |
| 5 mM | 0.3117 mL | 1.5584 mL | 3.1169 mL | |
| 10 mM | 0.1558 mL | 0.7792 mL | 1.5584 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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