ACIVICIN

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C5H7ClN2O3
Molecular Weight	178.574
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(CC(Cl)=NO1)[C@H](N)C(O)=O

InChI

InChIKey=QAWIHIJWNYOLBE-OKKQSCSOSA-N

InChI=1S/C5H7ClN2O3/c6-3-1-2(11-8-3)4(7)5(9)10/h2,4H,1,7H2,(H,9,10)/t2-,4-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C5H7ClN2O3
Molecular Weight	178.574
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9829740
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24411479 | https://www.ncbi.nlm.nih.gov/pubmed/8192104 | https://www.ncbi.nlm.nih.gov/pubmed/29032155 | https://www.ncbi.nlm.nih.gov/pubmed/2173394 | https://www.ncbi.nlm.nih.gov/pubmed/3530455 |

Acivicin is a modified amino acid and structural analog of glutamine, that irreversibly inhibits glutamine-dependent amidotransferases involved in nucleotide and amino acid biosynthesis. Acivicin is a potent antitumor agent that induces apoptosis in human lymphoblastoid cells. Phase I dose-escalating studies conducted in cancer patients administered acivicin showed reversible, dose-limiting CNS toxicity, characterized by lethargy, confusion and decreased mental status.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Gamma-glutamyltranspeptidase 1 2 Target ID: CHEMBL5696 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24411479	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Solid tumors 145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9829740	Primary	Phase I 428	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8192104	Primary	Phase II 1132	Unknown Approved Use Unknown
Hepatocellular carcinoma 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2173394	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2793383	Primary	Phase II 1132	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3530455	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Mechanism of S-(1,2-dichlorovinyl)glutathione-induced nephrotoxicity.	1986 Jan 15	2867768
Sequential oxidation and glutathione addition to 1,4-benzoquinone: correlation of toxicity with increased glutathione substitution.	1988 Dec	3200250
Inhibition of gamma-glutamyl transpeptidase potentiates the nephrotoxicity of glutathione-conjugated chlorohydroquinones.	1991 Aug	1678558
In vivo nephrotoxic action of an isomeric mixture of S-(1-phenyl-2-hydroxyethyl)glutathione and S-(2-phenyl-2-hydroxyethyl)glutathione in Fischer-344 rats.	1991 Mar 25	1673268
Endogenously formed leukotriene C4 activates LTC4 receptors in guinea pig tracheal strips.	1991 Mar 26	1651863
Nephrotoxicity of 4-amino-3-S-glutathionylphenol and its modulation by metabolism or transport inhibitors.	1994	7909430
Leukotrienes and alpha-naphthylisothiocyanate-induced liver injury.	1995 Jun 26	7624871
Role of the renal cysteine conjugate beta-lyase pathway in inhaled compound A nephrotoxicity in rats.	1998 Jun	9637657
Acivicin induces apoptosis independently of gamma-glutamyltranspeptidase activity.	2001 Aug 3	11478776
Concentration-dependent effects of endogenous S-nitrosoglutathione on gene regulation by specificity proteins Sp3 and Sp1.	2004 May 15	14766015
Contribution of acetaminophen-cysteine to acetaminophen nephrotoxicity II. Possible involvement of the gamma-glutamyl cycle.	2005 Jan 15	15629191
Role of gamma-glutamyl transpeptidase in redox regulation of K+ channel remodeling in postmyocardial infarction rat hearts.	2009 Aug	19419996
An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discovery.	2013 Mar	22996645

Patents

Sample Use Guides

In Vivo Use Guide

Patients were treated with acivicin on a 72-h continuous infusion schedule at doses ranging from 25 to 60 mg/m2/day every 3 weeks.

Route of Administration: Intravenous

In Vitro Use Guide

Colorimetric assay using MTT labeling reagent was separately performed with MCF-7 and OAW-42 cells to determine cell proliferation in presence of glutaminase and acivicin in vitro. Actively growing cells were seeded in three 96-well microtiter plates at a density of 1x10^4 cells/well. Triplicate wells were treated with the following: (1) culture medium only (control), (2) Acivicin 5mkM, (3) Acivicin 10mkM, (4) Acivicin 15mkM. Incubation times for the three plates was 24. 48 and 72 hr respectively after which cell proliferation assay (MTT assay) was performed using Cell Proliferation Kit I. Boehringer Mannheim, Germany (MTT, 1465007) according to manufacftirer’s instructions.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:15:52 GMT 2023` Edited by `admin` on `Fri Dec 15 15:15:52 GMT 2023`
Record UNII	O0X60K76I6
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ACIVICIN

Official Name

English

U-42126

Code

English

Acivicin [WHO-DD]

Common Name

English

AT-125

Code

English

U 42126

Code

English

NSC-163501

Code

English

ACIVICIN [USAN]

Common Name

English

U 42,126

Code

English

5-ISOXAZOLEACETIC ACID, .ALPHA.-AMINO-3-CHLORO-4,5-DIHYDRO-, (S-(R*,R*))-

Systematic Name

English

acivicin [INN]

Common Name

English

(αS,5S)-α-Amino-3-chloro-2-isoxazoline-5-acetic acid

Systematic Name

English

AT 125

Code

English

ACIVICIN [MART.]

Common Name

English

U-42,126

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C2158