ZAURATEGRAST

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H25BrN4O3
Molecular Weight	521.406
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)[C@H](CC1=CC=C(NC2=C3C=NC=CC3=CC=N2)C=C1)NC4=C(Br)C(=O)C45CCCCC5

InChI

InChIKey=KYHVWHYLKOHLKA-FQEVSTJZSA-N

InChI=1S/C26H25BrN4O3/c27-21-22(26(23(21)32)10-2-1-3-11-26)31-20(25(33)34)14-16-4-6-18(7-5-16)30-24-19-15-28-12-8-17(19)9-13-29-24/h4-9,12-13,15,20,31H,1-3,10-11,14H2,(H,29,30)(H,33,34)/t20-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C26H25BrN4O3
Molecular Weight	521.406
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800018251
Curator's Comment: Description was created based on several sources, including http://www.ingentaconnect.com/content/ben/cir/2012/00000008/00000002/art00004?crawler=true | https://www.ncbi.nlm.nih.gov/pubmed/24179032

Zaurategrast (CDP323) is an ethyl ester prodrug of CT7758, a potent carboxylic acid antagonist of integrin alpha4-beta1 (α4β1) or very late antigen 4 (VLA4). CDP323 was under development with UCB and Biogen Idec for the treatment of multiple sclerosis. Its development was discontinued in 2009 based on inadequate interim efficacy data in a phase II clinical trial.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Integrin alpha-4/beta-1 6 Target ID: CHEMBL1907599 Sources: http://www.ingentaconnect.com/content/ben/cir/2012/00000008/00000002/art00004?crawler=true	Antagonist 2778
Acyl coenzyme A:cholesterol acyltransferase 15 Target ID: CHEMBL2265 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24179032	Substrate 661

Conditions

Condition	Modality	Targets	Highest Phase	Product
Multiple sclerosis 104 Sources: http://adisinsight.springer.com/drugs/800018251 http://www.ucb.com/our-science/Our-clinical-studies/CDP323	Primary		Phase II 1132	Unknown Approved Use Unknown

AUC

Value	Dose	Co-administered	Analyte	Population
0.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26153275	500 mg/kg single, oral dose: 500 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		ZAURATEGRAST plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1000 mg 2 times / day multiple, oral Highest studied dose Dose: 1000 mg, 2 times / day Route: oral Route: multiple Dose: 1000 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23472197 Page: p.7, 8	unhealthy, ADULT n = 14 Health Status: unhealthy Condition: multiple sclerosis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/23472197 Page: p.7, 8	Sources: https://pubmed.ncbi.nlm.nih.gov/23472197 Page: p.7, 8

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537 CYPs 33

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363678181	inconclusive [IC50 15.0916 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363678181	inconclusive [IC50 23.9185 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363678181	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678181	no
CYPs 33	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24179032/	yes

PubMed

Title	Date	PubMed
Pharmacodynamic consequences of administration of VLA-4 antagonist CDP323 to multiple sclerosis subjects: a randomized, double-blind phase 1/2 study.	2013	23472197

Patents

Sample Use Guides

In Vivo Use Guide

Multiple sclerosis subjects were randomized to 28-day treatment with Zaurategrast (CDP323) 100 mg twice daily (bid), 500 mg bid, 1000 mg once daily (qd), 1000 mg bid, or placebo. CDP323 at daily doses of 1000 or 2000 mg induced significant increases in total lymphocyte count and suppressed VCAM-1 binding by reducing unbound very late antigen-4 expression on lymphocytes.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:33:37 GMT 2023` Edited by `admin` on `Sat Dec 16 17:33:37 GMT 2023`
Record UNII	06A0IC74I3
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ZAURATEGRAST

Official Name

English

N-(2-BROMO-3-OXOSPIRO(3.5)NON-1-EN-1-YL)-4-(2,7-NAPHTHYRIDIN-1-YLAMINO)-L-PHENYLALANINE

Common Name

English

CT-7758

Code

English

CT7758

Code

English

(2S)-2-((2-BROMO-3-OXOSPIRO(3.5)NON-1-EN-1-YL)AMINO)-3-(4-((2,7-NAPHTHYRIDIN-1-YL)AMINO)PHENYL)PROPANOIC ACID

Systematic Name

English

Zaurategrast [WHO-DD]

Common Name

English

zaurategrast [INN]

Common Name

English

L-PHENYLALANINE, N-(2-BROMO-3-OXOSPIRO(3.5)NON-1-EN-1-YL)-4-(2,7-NAPHTHYRIDIN-1-YLAMINO)-

Common Name

English

(S)-3-(4-((2,7-NAPHTHYRIDIN-1-YL)AMINO)PHENYL)-2-((2-BROMO-3-OXOSPIRO(3.5)NON-1-EN-1-YL)AMINO)PROPANOIC ACID

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29712