AV-101

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H11ClN2O3
Molecular Weight	242.659
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N[C@@H](CC(=O)C1=CC=C(Cl)C=C1N)C(O)=O

InChI

InChIKey=HQLHZNDJQSRKDT-QMMMGPOBSA-N

InChI=1S/C10H11ClN2O3/c11-5-1-2-6(7(12)3-5)9(14)4-8(13)10(15)16/h1-3,8H,4,12-13H2,(H,15,16)/t8-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C10H11ClN2O3
Molecular Weight	242.659
Charge	0
Count

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

Description
Sources: https://adisinsight.springer.com/drugs/800008781 | https://clinicaltrials.gov/ct2/show/NCT02484456 | https://www.ncbi.nlm.nih.gov/pubmed/29229209

4‐Chlorokynurenine (AV-101) is a neuropharmaceutical drug candidate in development for the treatment of major depressive disorder. Pharmacology studies conducted in rodent models have demonstrated AV-101’s antihyperalgesic activity in models of facilitated pain processing was seen at serum concentrations ranging from 150–300 M. In addition, AV-101 has been shown to be neuroprotective activity against an intrahippocampal injection of quinolinic acid, reductions in seizures, and antidepressive activity. An oral prodrug, AV-101, which, in the brain, is converted into one of the most potent and selective GlyB site antagonists of the NMDAR, has been demonstrated to be active in animal models of neuropathic pain. The two Phase 1 studies were designed to assess the safety and pharmacokinetics of AV-101, over a wide dose range, after daily dosing for 14-days. AV-101 has excellent safety and PK characteristics providing support for advancing AV-101 into Phase 2 studies in neuropathic pain.

CNS Activity

Originator

Approval Year

PubMed

Title	Date	PubMed
Systemic administration of 4-chlorokynurenine prevents quinolinate neurotoxicity in the rat hippocampus.	2000 Mar 3	10708733
Randomized, double-blind, placebo-controlled, dose-escalation study: Investigation of the safety, pharmacokinetics, and antihyperalgesic activity of l-4-chlorokynurenine in healthy volunteers.	2017 Oct	29229209
4-Chloro-L-kynurenine as fluorescent amino acid in natural peptides.	2018 Dec	30178101
Biosynthesis of l-4-Chlorokynurenine, an Antidepressant Prodrug and a Non-Proteinogenic Amino Acid Found in Lipopeptide Antibiotics.	2019 Jun 17	30963655

Patents

Sample Use Guides

In Vivo Use Guide

The Phase 1A study was a single-site, randomized, double-blind, placebo-controlled, single oral ascending dose (30–1800 mg) study involving 36 normal healthy volunteers. The Phase 1B study was a single-site randomized, double-blind, placebo-controlled, study of multiple ascending doses (360, 1080, and 1440 mg/day) of AV-101 involving 50 normal healthy volunteers, to whom AV-101 or placebo were administered orally daily for 14 consecutive days. Two Phase 1, with an aggregate of 86 subjects, demonstrated that up to 14 days of oral AV-101, up to 1440 mg per day, was safe and very well tolerated.

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:01:42 GMT 2023` Edited by `admin` on `Sat Dec 16 08:01:42 GMT 2023`
Record UNII	77XLH9L40B
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AV-101

Common Name

English

(2S)-2-AMINO-4-(2-AMINO-4-CHLOROPHENYL)-4-OXOBUTANOIC ACID

Systematic Name

English

L-4-CHLOROKYNURENINE

Common Name

English

BENZENEBUTANOIC ACID, .ALPHA.,2-DIAMINO-4-CHLORO-.GAMMA.-OXO-, (S)

Systematic Name

English

L-4-CL-KYN

Common Name

English

4-CHLOROKYNURENINE

Common Name

English

4-CL-KYN

Common Name

English

J578.071C

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1509