E-7820

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H12N4O2S
Molecular Weight	336.368
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=C(NS(=O)(=O)C2=CC=CC(=C2)C#N)C3=C1C(=CN3)C#N

InChI

InChIKey=LWGUASZLXHYWIV-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/30913493 | https://www.ncbi.nlm.nih.gov/pubmed/21208908 | https://www.ncbi.nlm.nih.gov/pubmed/14977846 | https://www.ncbi.nlm.nih.gov/pubmed/12414636

E-7820 is a novel angiogenesis inhibitor. It inhibited in vitro proliferation and tube formation of human umbilical vascular endothelial cell (HUVEC). E-7820 decreased integrin alpha 2, 3, 5, and beta 1 in confluent culture of HUVEC, and integrin alpha 2 was initially suppressed in mRNA level, followed by decrement of integrins alpha 3, 5, and beta 1. Up-regulation of integrin alpha2 by phorbol 12-myristate 13-acetate abrogated the inhibitory effect of E7820 on tube formation within type I collagen gel, whereas addition of antibody against integrin alpha2 canceled the phorbol 12-myristate 13-acetate effect. This finding may provide the basis for a new approach to antiangiogenic therapy through the suppression of integrin alpha2 on endothelium. E-7820 showed a broad-spectrum antitumor effect in mice through inhibition of angiogenesis and indicate that the decrease of integrin alpha2 on platelets might serve as a biological marker for the antitumor efficacy of E-7820. Combining E-7820 and chemotherapeutic agents to block the integrin α2β1/PI3K/AKT/Snail signaling pathway revealed dramatically enhanced tumor suppression and provided an innovative approach for clinical colorectal cancer treatment.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Integrin alpha-2 3 Target ID: CHEMBL4998 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12414636	Inhibitor 8504

C_max

Value	Dose	Analyte	Population
1030 ng/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
901 ng/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1150 ng/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg 2 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1310 ng/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1486.9 ng/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2068.3 ng/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1880 ng/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2950 ng/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	60 mg 2 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
0.19 μg/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.45 μg/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
0.74 μg/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.77 μg/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1.86 μg/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
11200 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
11500 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6780 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg 2 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
9620 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	60 mg 2 times / day multiple, oral dose: 60 mg route of administration: Oral experiment type: MULTIPLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14760.3 ng × h/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
20331.2 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	100 mg 1 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
14500 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
26500 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	60 mg 2 times / day steady-state, oral dose: 60 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.2 μg × h/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
2.8 μg × h/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
5.3 μg × h/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
17.7 μg × h/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
21.6 μg × h/mL EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
10.2 h EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
11.7 h EXPERIMENT https://link.springer.com/article/10.1007/s10637-016-0344-9	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
6.58 h EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
5.6 h EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
6.37 h EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
7.054 h EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	40 mg single, oral dose: 40 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
6.3 h EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	70 mg single, oral dose: 70 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
8.6 h EXPERIMENT https://aacrjournals.org/clincancerres/article/17/1/193/76096/Phase-I-Study-of-E7820-an-Oral-Inhibitor-of	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	E-7820 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

PubMed

Title	Date	PubMed
Collagen facilitates the colorectal cancer stemness and metastasis through an integrin/PI3K/AKT/Snail signaling pathway.	2019-06	30913493
Phase I study of E7820, an oral inhibitor of integrin alpha-2 expression with antiangiogenic properties, in patients with advanced malignancies.	2011-01-01	21208908
Small molecule integrin antagonists in cancer therapy.	2009-10	19929817
Application of population pharmacokinetic modeling in early clinical development of the anticancer agent E7820.	2009-04	18712503
Integrins: molecular targets in cancer therapy.	2006-03	16507218
An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker.	2004-02-15	14977846
Sulfonamide derivative, E7820, is a unique angiogenesis inhibitor suppressing an expression of integrin alpha2 subunit on endothelium.	2002-11-01	12414636

Sample Use Guides

In Vivo Use Guide

The recommended is 100 mg/day

Route of Administration: Oral

Name

Type

Language

E7820

Preferred Name

English

E-7820

Common Name

English

ER-68203-00

Code

English

BENZENESULFONAMIDE, 3-CYANO-N-(3-CYANO-4-METHYL-1H-INDOL-7-YL)-

Systematic Name

English

N-(3-CYANO-4-METHYL-1H-INDOL-7-YL)-3-CYANOBENZENE-SULFONAMIDE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2144