TAK-779 CATION

Details

Stereochemistry	ACHIRAL
Molecular Formula	C33H39N2O2
Molecular Weight	495.675
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=C(C=C1)C2=CC=C3CCCC(=CC3=C2)C(=O)NC4=CC=C(C[N+](C)(C)C5CCOCC5)C=C4

InChI

InChIKey=XNHZXMPLVSJQFK-UHFFFAOYSA-O

InChI=1S/C33H38N2O2/c1-24-7-11-27(12-8-24)28-14-13-26-5-4-6-29(22-30(26)21-28)33(36)34-31-15-9-25(10-16-31)23-35(2,3)32-17-19-37-20-18-32/h7-16,21-22,32H,4-6,17-20,23H2,1-3H3/p+1

HIDE SMILES / InChI

Molecular Formula	C33H39N2O2
Molecular Weight	495.675
Charge	1
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12142563 | https://www.ncbi.nlm.nih.gov/pubmed/11575704

TAK-779 is a selective antagonist of CCR5 receptor, which was initially developed by Takeda for the treatment of HIV infection. However, the development was terminated due to poor oral bioavailability. Also, TAK-779 demonstrated the ability to protect the brain against focal cerebral ischemia in mice.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
C-C chemokine receptor type 5 19 Target ID: P51681\|\|\|O14700\|\|\|O14708 Gene ID: 1234.0 Gene Symbol: CCR5 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/10318947	Antagonist 2778	1.1 nM [Ki]
C-C chemokine receptor type 5 19 Target ID: CHEMBL274 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10318947	Inhibitor 8297	1.4 nM [IC50]
C-C chemokine receptor type 2 17 Target ID: CHEMBL4015 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10318947	Inhibitor 8297	27.0 nM [IC50]
Human immunodeficiency virus 1 33 Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10318947	Inhibitor 8297	1.2 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV infection 21 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11575704	Primary		Preclinical	Unknown Approved Use Unknown
Focal cerebral ischemia 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12142563	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity.	1999 May 11	10318947
CXCR3 antagonist VUF10085 binds to an intrahelical site distinct from that of the broad spectrum antagonist TAK-779.	2015 Apr	25425280

Sample Use Guides

In Vivo Use Guide

In a mouse model of ischemic brain injury, TAK-779 (25 or 250 ng in 5 uL) was administered by intracerebroventricular injection (1.0 mm lateral, 0.5 mm posterior, 3.0 mm ventral to bregma) at 10 minutes before MCA occlusion, or by intravenous injection (5 ug/100 uL per 20 g body weight).

Route of Administration: Other

In Vitro Use Guide

The effect of TAK-779 on virus replication in PBMC was assayed after incubation of cells for 30 min with a range of concentrations of the inhibitor (0.01 to 100 uM) prior to infection with the UK1-br and MACS2-br primary isolates. IC50 values were 70 and 4 uM, respectively.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:13:55 GMT 2023` Edited by `admin` on `Sat Dec 16 11:13:55 GMT 2023`
Record UNII	RN3X97C29H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TAK-779 CATION

Common Name

English

2H-PYRAN-4-AMINIUM, N-((4-(((6,7-DIHYDRO-2-(4-METHYLPHENYL)-5H-BENZOCYCLOHEPTEN-8-YL)CARBONYL)AMINO)PHENYL)METHYL)TETRAHYDRO-N,N-DIMETHYL-

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID20180974

Created by admin on Sat Dec 16 11:13:55 GMT 2023 , Edited by admin on Sat Dec 16 11:13:55 GMT 2023

PRIMARY

PUBCHEM

183790

Created by admin on Sat Dec 16 11:13:55 GMT 2023 , Edited by admin on Sat Dec 16 11:13:55 GMT 2023

PRIMARY

FDA UNII

RN3X97C29H

Created by admin on Sat Dec 16 11:13:55 GMT 2023 , Edited by admin on Sat Dec 16 11:13:55 GMT 2023

PRIMARY

CAS

263765-56-6

Created by admin on Sat Dec 16 11:13:55 GMT 2023 , Edited by admin on Sat Dec 16 11:13:55 GMT 2023

PRIMARY

Related Record Type Details


					F5Q48O042G

C-C CHEMOKINE RECEPTOR TYPE 5

TARGET -> INHIBITOR

Comments:

TAK-779 as an extremely potent antagonist of CCR5, which completely inhibited the binding of [125I]-RANTES to CHO/CCR5 cells at a concentration of 100 nM (Fig. (Fig.22C). Its 50% inhibitory concentration (IC50) for the binding was 1.4 nM.

Interaction Type:

BINDING

Qualification:

IC50

Amount:


					BQW1Y9KIIP

TAK-779

SALT/SOLVATE -> PARENT


					F5Q48O042G

C-C CHEMOKINE RECEPTOR TYPE 5

TARGET -> INHIBITOR

Comments:

TAK-779 completely inhibited R5 HIV-1 (Ba-L strain) replication in MAGI-CCR5 cells at a concentration of 32 nM. Its 50% and 90% effective concentrations (EC50 and EC90) were 1.2 and 5.7 nM, respectively. However, TAK-779 did not affect X4 HIV-1 (IIIB strain) replication at concentrations up to 20 μM.

Interaction Type:

BINDING

Qualification:

EC50

Amount:

Related Record Type Details


					RN3X97C29H

TAK-779 CATION

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/12142563 | https://www.ncbi.nlm.nih.gov/pubmed/11575704

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

PubMed

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12142563 | https://www.ncbi.nlm.nih.gov/pubmed/11575704