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

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

Molecular Formula	C17H12N4O2S
Molecular Weight	336.368
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

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

Targets

Primary Target	Pharmacology	Condition	Potency
Integrin alpha-2 3	Inhibitor 8,504

C_max

Value	Dose	Analyte	Population
1030 ng/mL	50 mg single, oral	E-7820 plasma	Homo sapiens
901 ng/mL	50 mg single, oral	E-7820 plasma	Homo sapiens
1150 ng/mL	50 mg 2 times / day multiple, oral	E-7820 plasma	Homo sapiens
1310 ng/mL	60 mg 2 times / day multiple, oral	E-7820 plasma	Homo sapiens
1486.9 ng/mL	100 mg single, oral	E-7820 plasma	Homo sapiens
2068.3 ng/mL	100 mg 1 times / day steady-state, oral	E-7820 plasma	Homo sapiens
1880 ng/mL	50 mg 2 times / day steady-state, oral	E-7820 plasma	Homo sapiens
2950 ng/mL	60 mg 2 times / day steady-state, oral	E-7820 plasma	Homo sapiens
0.19 μg/mL	10 mg single, oral	E-7820 plasma	Homo sapiens
0.45 μg/mL	20 mg single, oral	E-7820 plasma	Homo sapiens
0.74 μg/mL	40 mg single, oral	E-7820 plasma	Homo sapiens
1.77 μg/mL	70 mg single, oral	E-7820 plasma	Homo sapiens
1.86 μg/mL	200 mg single, oral	E-7820 plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
11200 ng × h/mL	50 mg single, oral	E-7820 plasma	Homo sapiens
11500 ng × h/mL	50 mg single, oral	E-7820 plasma	Homo sapiens
6780 ng × h/mL	50 mg 2 times / day multiple, oral	E-7820 plasma	Homo sapiens
9620 ng × h/mL	60 mg 2 times / day multiple, oral	E-7820 plasma	Homo sapiens
14760.3 ng × h/mL	100 mg single, oral	E-7820 plasma	Homo sapiens
20331.2 ng × h/mL	100 mg 1 times / day steady-state, oral	E-7820 plasma	Homo sapiens
14500 ng × h/mL	50 mg 2 times / day steady-state, oral	E-7820 plasma	Homo sapiens
26500 ng × h/mL	60 mg 2 times / day steady-state, oral	E-7820 plasma	Homo sapiens
1.2 μg × h/mL	10 mg single, oral	E-7820 plasma	Homo sapiens
2.8 μg × h/mL	20 mg single, oral	E-7820 plasma	Homo sapiens
5.3 μg × h/mL	40 mg single, oral	E-7820 plasma	Homo sapiens
17.7 μg × h/mL	70 mg single, oral	E-7820 plasma	Homo sapiens
21.6 μg × h/mL	200 mg single, oral	E-7820 plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
10.2 h	50 mg single, oral	E-7820 plasma	Homo sapiens
11.7 h	50 mg single, oral	E-7820 plasma	Homo sapiens
6.58 h	100 mg single, oral	E-7820 plasma	Homo sapiens
5.6 h	10 mg single, oral	E-7820 plasma	Homo sapiens
6.37 h	20 mg single, oral	E-7820 plasma	Homo sapiens
7.054 h	40 mg single, oral	E-7820 plasma	Homo sapiens
6.3 h	70 mg single, oral	E-7820 plasma	Homo sapiens
8.6 h	200 mg single, oral	E-7820 plasma	Homo sapiens

PubMed

PubMed

Show entries

Title	Date	PubMed
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 Feb 15	14977846
Integrins: molecular targets in cancer therapy.	2006 Mar	16507218
Application of population pharmacokinetic modeling in early clinical development of the anticancer agent E7820.	2009 Apr	18712503
Collagen facilitates the colorectal cancer stemness and metastasis through an integrin/PI3K/AKT/Snail signaling pathway.	2019 Jun	30913493

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Sample Use Guides

In Vivo Use Guide

The recommended is 100 mg/day

Route of Administration: Oral

Substance Class	Chemical
Record UNII	TVH5K7949N
Record Status	`Validated (UNII)`
Record Version

Show entries

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

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Classification Tree

Code System

Code

Angiogenesis Inhibitor

NCI_THESAURUS

C2144

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Code System

Code

Type

Description

FDA UNII

TVH5K7949N

PRIMARY

PUBCHEM

196970

PRIMARY

CAS

289483-69-8

PRIMARY

SMS_ID

100000175114

PRIMARY

EPA CompTox

DTXSID20183142

PRIMARY

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Related Record

Type

Details


					TVH5K7949N

E-7820

ACTIVE MOIETY

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SMILES

InChI

Approval Year

Targets

Cmax

AUC

T1/2

PubMed

Sample Use Guides

C_max

T_1/2