Name: E 7820
Brand: BOC Sciences
Rating: 5 (1 reviews)

Purity

≥95%

Solubility

Soluble in DMF, DMSO, Ethanol

Appearance

Beige Solid

ShelfLife

>2 years if stored properly

Storage

Store at -20°C

Shipping

Room temperature in continental US; may vary elsewhere.

IUPACName

3-cyano-N-(3-cyano-4-methyl-1H-indol-7-yl)benzenesulfonamide

Synonyms

ER68203-00; N-(3-Cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzene-sulfonamide; NSC-719239; 3-cyano-N-(3-cyano-4-methyl-1H-indol-7-yl)benzene-1-sulfonamide; Benzenesulfonamide, 3-cyano-N-(3-cyano-4-methyl-1H-indol-7-yl)-

Boiling Point

626.2±65.0°C (Predicted)

Density

1.48±0.1 g/cm3 (Predicted)

Chemical Name

3-Cyano-N-(3-cyano-4-methyl-1H-indol-7-yl)benzenesulfonamide

InChI Key

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

InChI

LWGUASZLXHYWIV-UHFFFAOYSA-N

SMILES

O=S(C1=CC=CC(C#N)=C1)(NC2=CC=C(C)C3=C2NC=C3C#N)=O

Biological Activity

α2 integrin inhibitor. Inhibits angiogenesis in vitro (IC50 = 0.11 - 0.25 μM). Also inhibits growth of human colorectal cancer cell lines. Enhances efficacy of erlotinib in a non-small-cell lung cancer xenograft model. Also acts as a molecular glue to induce proteosomal degradation of mRNA splicing factor RBM39.

Mechanism

E3 Ligase: E7820 recruits the DCAF15 E3 ligase complex, facilitating the selective ubiquitination of its target protein. This interaction stabilizes the ternary complex between DCAF15 and the neosubstrate, enabling efficient degradation.

Target Protein: The primary target of E7820 is RBM39, an RNA-binding protein involved in pre-mRNA splicing and transcriptional regulation. By engaging RBM39, E7820 modulates RNA processing pathways and disrupts cellular transcriptional programs.

Degradation Mechanism: E7820 mediates proteasomal degradation of RBM39 through the ubiquitin–proteasome system. Formation of the DCAF15–RBM39 ternary complex promotes polyubiquitination, leading to recognition and clearance by the 26S proteasome, resulting in effective depletion of RBM39 in cells.

Applications

• Molecular Glue-mediated Protein Degradation: E 7820 serves as a potent molecular glue, facilitating the targeted degradation of specific proteins by promoting the interaction between E3 ubiquitin ligases and their substrates. This mechanism enables researchers to selectively degrade proteins of interest, thereby providing insights into protein function and potential therapeutic targets.

• Targeted Protein Degradation in Cancer Research: Leveraging E 7820 in cancer studies allows for the exploration of novel degradation pathways. By inducing the selective degradation of oncogenic proteins, this ligand aids in elucidating cancer cell vulnerabilities and contributes to the development of innovative therapeutic strategies.

• Molecular Glue in Drug Discovery: E 7820's ability to act as a molecular glue offers a unique approach in drug discovery. Researchers can utilize this product to identify and validate new drug targets by observing the effects of targeted protein degradation on cellular pathways, thus accelerating the drug development process.

• Enhancing Proteomics Studies: Utilizing E 7820 in proteomics facilitates the study of protein interactions and stability. By promoting targeted degradation, this ligand aids in the dissection of complex proteomic networks, allowing scientists to better understand protein dynamics and their implications in various biological processes.

1.Phase I study of E7820, an oral inhibitor of integrin alpha-2 expression with antiangiogenic properties, in patients with advanced malignancies.

Mita M1, Kelly KR, Mita A, Ricart AD, Romero O, Tolcher A, Hook L, Okereke C, Krivelevich I, Rossignol DP, Giles FJ, Rowinsky EK, Takimoto C. Clin Cancer Res. 2011 Jan 1;17(1):193-200. doi: 10.1158/1078-0432.CCR-10-0010.

PURPOSE: This phase I study was conducted to characterize the safety profile, pharmacokinetics, pharmacodynamics, dose-limiting toxicity (DLT), and the maximum-tolerated dose of E7820, a novel oral sulfonamide derivative with antiangiogenic properties, when administered to patients with advanced solid malignancies.

2.Enhanced anti-angiogenic effect of E7820 in combination with erlotinib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small-cell lung cancer xenograft models.

Ito K1, Semba T, Uenaka T, Wakabayashi T, Asada M, Funahashi Y. Cancer Sci. 2014 Aug;105(8):1023-31. doi: 10.1111/cas.12450.

Most non-small-cell lung cancers (NSCLCs) harboring activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (EGFR-TKIs); however, they invariably develop resistance to these drugs. E7820 is an angiogenesis inhibitor that decreases integrin-α2 expression and is currently undergoing clinical trials. We investigated whether E7820 in combination with erlotinib, an EGFR-TKI, could overcome EGFR-TKI-resistance in the NSCLC cell lines A549 (KRAS; G12S), H1975 (EGFR; L858R/T790M), and H1650 (PTEN; loss, EGFR; exon 19 deletion), which are resistant to erlotinib. Immunohistochemical analysis was carried out in xenografted tumors to investigate anti-angiogenesis activity and endothelial cell apoptosis levels by endothelial cell marker CD31 and TUNEL staining, respectively. Treatment with E7820 (50 mg/kg) with erlotinib (60 mg/kg) showed a synergistic antitumor effect in three xenograft models.

3.Application of population pharmacokinetic modeling in early clinical development of the anticancer agent E7820.

Keizer RJ1, Zamacona MK, Jansen M, Critchley D, Wanders J, Beijnen JH, Schellens JH, Huitema AD. Invest New Drugs. 2009 Apr;27(2):140-52. doi: 10.1007/s10637-008-9164-x. Epub 2008 Aug 20.

The aim of this study was to assess the population pharmacokinetics (PopPK) of the novel oral anti-cancer agent E7820. Both a non-linear mixed effects modeling analysis and a non-compartmental analysis (NCA) were performed and results were compared. Data were obtained from a phase I dose escalation study in patients with malignant solid tumors or lymphomas. E7820 was administered daily for 28 days, followed by a washout period of 7 days prior to the start of subsequent cycles. A one compartment model with linear elimination from the central compartment was shown to give adequate fit, while absorption was described using a turnover model. Final population parameter estimates of basic PK parameters obtained with the PopPK method were (RSE): clearance, 6.24 L/h (7.1%), volume of distribution, 66.0 L (8.5%), mean transit time to the absorption compartment, 0.638 h (6.5%). The intake of food prior to dose administration slowed absorption (2.8-fold, RSE 13%) and increased relative bioavailability of E7820 by 36% (RSE 14%), although the effect on C (max) and AUC was not significant.

ConcentrationVolumeMass	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

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂