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Purity: ≥98%
E7820 (E-7820) is a novel and potent angiogenesis inhibitor and α2 integrin inhibitor with anticancer activity. It decreases integrin-α2 expression and is currently undergoing clinical trials. It is a small molecule and aromatic sulfonamide derivative with potential antiangiogenic and antitumor activities. E7820 inhibits angiogenesis by suppressing integrin alpha 2, a cell adhesion molecule expressed on endothelial cells. Inhibition of integrin alpha 2 leads to an inhibition of cell-cell interactions, endothelial cell-matrix interactions, vascular endothelial cell proliferation and angiogenesis. The combination of E7820 with erlotinib is an alternative strategy to overcome erlotinib resistance in NSCLC by enhancement of the anti-angiogenic activity of E7820.
| Targets |
E7820 targets integrin alpha2 subunit. [1]
E7820 acts on integrin alpha2 subunit to exert anti-angiogenic effects . [2] |
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| ln Vitro |
E7820 (ER68203-00) suppresses human umbilical vascular endothelial cell (HUVEC) ube production driven by both bFGF and VEGF in a dose-dependent manner, with IC50 values of 0.20 and 0.24 μg/ml, respectively[1]. E7820 prevents HUVEC from proliferating in serum-free medium (SFM) when it is stimulated by VEGF or bFGF. The respective IC50 values are 0.10 and 0.081 μg/ml. When compared to HUVEC, E7820's antiproliferative effect against WiDr and LoVo cells is incredibly weak. [1] The IC50 values were 15 and 29 μg/ml, respectively.
1. E7820 inhibits the proliferation and tube formation of human umbilical vascular endothelial cells (HUVEC) in vitro. In confluent HUVEC cultures, it reduces the expression of integrin alpha2, alpha3, alpha5, and beta1; integrin alpha2 is first suppressed at the mRNA level, followed by a decrease in integrins alpha3, alpha5, and beta1. The suppression of integrin alpha2 expression by E7820 shows dose dependence, but it does not alter the expression level of CD31. Up-regulation of integrin alpha2 by phorbol 12-myristate 13-acetate (PMA) abrogates the inhibitory effect of E7820 on tube formation in type I collagen gel, while the addition of an antibody against integrin alpha2 cancels this PMA-induced effect. [1] 2. When combined with erlotinib, E7820 synergistically enhances apoptosis in HUVECs in vitro through the activation of both intrinsic and extrinsic apoptosis pathways. The combination treatment inhibits cell proliferation in HUVECs and H1650 non-small-cell lung cancer (NSCLC) cells but has no significant inhibitory effect on the proliferation of A549 and H1975 NSCLC cells. [2] |
| ln Vivo |
E7820 (ER68203-00) slows the proliferation of WiDr cells that have been injected with sc. (50-200 mg/kg; po; twice daily for 14 days)[1]. ?A powerful inhibitor of WiDr-induced angiogenesis, E7820 (200–400 mg/kg; po; once daily for 4 days) has been reported[1].
1. Oral administration of E7820 significantly inhibits tumor-induced angiogenesis in the mouse dorsal air sac model. Additionally, it suppresses the tumor growth of human colorectal cancer cell lines (WiDr and LoVo) in a mouse xenograft model. [1] 2. In three erlotinib-resistant NSCLC xenograft models (A549 with KRAS G12S mutation, H1975 with EGFR L858R/T790M mutations, and H1650 with PTEN loss and EGFR exon 19 deletion), combination treatment with E7820 (50 mg/kg) and erlotinib (60 mg/kg) exerts a synergistic antitumor effect. Immunohistochemical analysis shows that the combined treatment significantly reduces microvessel density (assessed by CD31 staining) and increases the apoptosis of tumor-associated endothelial cells (assessed by TUNEL staining) compared to monotherapy. Furthermore, the combination inhibits tumor cell proliferation (assessed by proliferating cell nuclear antigen, PCNA, staining) and enhances tumor cell apoptosis (assessed by TUNEL staining) in xenografted tumors. [2] |
| Cell Assay |
Tumor cells are plated at 1 to 2×105 cells/well on 96-well plates in 0.1 mL of RPMI 1640 containing 10% fetal bovine serum. After 24 h, either E7820 or vehicle is added to duplicate cultures of cells, and at 2 or 3 days after addition of E7820, the ratios of surviving cells are measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. All experiments are done at least in duplicate and repeated twice.
1. HUVEC functional and integrin expression assays: HUVECs are cultured until confluent. The cells are treated with E7820, and the expression levels of integrin alpha2, alpha3, alpha5, and beta1 are detected (including mRNA level analysis for integrin alpha2). The tube formation ability of HUVECs in type I collagen gel is evaluated. To verify the role of integrin alpha2, HUVECs are pretreated with PMA to up-regulate integrin alpha2, then treated with E7820 to observe changes in tube formation inhibition. Subsequently, an antibody against integrin alpha2 is added to determine if it can reverse the PMA-induced abrogation of E7820’s effect. The expression level of CD31 is also measured to exclude non-specific effects on endothelial cell markers. [1] 2. Cell proliferation and apoptosis assays: HUVECs, A549, H1975, and H1650 cells are cultured in appropriate media. The cells are treated with E7820 alone or in combination with erlotinib for 48 or 96 hours, and cell proliferation is analyzed. Apoptosis is detected using annexin V–propidium iodide (PI) two-color flow cytometry. The loss of mitochondrial membrane potential (MMP) is measured to assess intrinsic apoptosis pathway activation. Western blot analysis is performed to detect the mitochondrial release of cytochrome c. Caspase-3-like activity is quantified to evaluate downstream apoptotic signaling. Additionally, cells are treated with E7820 and erlotinib in the presence or absence of broad-spectrum caspase inhibitor (zVAD-fmk) or specific inhibitors of caspase-3, caspase-9, and caspase-8 to confirm the involvement of both intrinsic and extrinsic apoptosis pathways. [2] |
| Animal Protocol |
Animal/Disease Models: Sixweeks old female nude mice (KSN mice, WiDr-induced angiogenesis model) [1]
Doses: 50, 100, 200 mg/kg Route of Administration: po; twice (two times) daily for 14 days from 2 days after inoculation of the tumor cells Experimental Results: The antitumor effect was dose-dependent at 50, 100, and 200 mg/kg, and the tumor growth rates were 52%, 46%, and 27%, respectively. 1. Mouse dorsal air sac angiogenesis model: Mice are used to establish the dorsal air sac model. E7820 is administered orally (specific frequency not provided), and the degree of tumor-induced angiogenesis is evaluated after the experimental period. [1] 2. Human colorectal cancer xenograft model: Nude mice are implanted with human colorectal cancer cell lines (WiDr or LoVo) to establish xenograft tumors. E7820 is given via oral administration (specific frequency not provided), and tumor growth is monitored and measured to assess the inhibitory effect. [1] 3. Erlotinib-resistant NSCLC xenograft models: Nude mice are implanted with erlotinib-resistant NSCLC cell lines (A549, H1975, or H1650) to form xenograft tumors. Once tumors reach an appropriate size, the mice are divided into groups (n = 5–6 per group) and treated with vehicle, E7820 (50 mg/kg), erlotinib (60 mg/kg), or their combination for 7 days. After treatment, tumors are resected and processed for immunohistochemical analysis (CD31 staining for microvessel density, PCNA staining for cell proliferation) and TUNEL staining for apoptosis detection. The specific drug dissolution formulation is not provided. [2] |
| References |
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| Additional Infomation |
E7820 has been studied for the treatment of colon and rectal cancer.
E7820, an integrin α-2 inhibitor, is a small molecule aromatic sulfonamide derivative with potential anti-angiogenic and antitumor activity. E7820 inhibits angiogenesis by inhibiting the cell adhesion molecule integrin α-2 expressed on endothelial cells. Inhibition of integrin α-2 inhibits cell-cell interactions, endothelial cell-matrix interactions, vascular endothelial cell proliferation and angiogenesis. 1. E7820 is a novel aromatic sulfonamide derivative and a unique angiogenesis inhibitor. [1] 2. E7820 exerts its anti-angiogenic effect by inhibiting the expression of integrin α2 subunits on endothelial cells. It is the first small molecule to be shown to regulate integrins, providing a new strategy for anti-angiogenic therapy. [1] 3. At the time of this study, E7820 was undergoing clinical trials. [2] 4. Combining E7820 with erlotinib is another strategy to overcome erlotinib resistance in non-small cell lung cancer, as it can enhance the anti-angiogenic activity of E7820. [2] |
| Molecular Formula |
C17H12N4O2S
|
|---|---|
| Molecular Weight |
336.367781639099
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| Exact Mass |
336.068
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| CAS # |
289483-69-8
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| PubChem CID |
196970
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| Appearance |
Light yellow to light brown solid powder
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| Density |
1.48g/cm3
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| Boiling Point |
626.2ºC at 760mmHg
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| Flash Point |
332.5ºC
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| Vapour Pressure |
1.34E-15mmHg at 25°C
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| Index of Refraction |
1.719
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| LogP |
4.174
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
|
| Heavy Atom Count |
24
|
| Complexity |
668
|
| Defined Atom Stereocenter Count |
0
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| InChi Key |
LWGUASZLXHYWIV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H12N4O2S/c1-11-5-6-15(17-16(11)13(9-19)10-20-17)21-24(22,23)14-4-2-3-12(7-14)8-18/h2-7,10,20-21H,1H3
|
| Chemical Name |
N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzene-sulfonamide
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| Synonyms |
ER68203-00; E7820; ER 68203-00; E-7820; ER-68203-00; E 7820
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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) |
DMSO : ~100 mg/mL (~297.29 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.43 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9729 mL | 14.8646 mL | 29.7292 mL | |
| 5 mM | 0.5946 mL | 2.9729 mL | 5.9458 mL | |
| 10 mM | 0.2973 mL | 1.4865 mL | 2.9729 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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