AVL-3288

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H15Cl2N3O2
Molecular Weight	388.247
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=NOC(=C1)C(=C\NC2=CC=C(Cl)C=C2)\C(=O)NC3=CC=C(Cl)C=C3

InChI

InChIKey=VMAKIACTLSBBIY-BOPFTXTBSA-N

InChI=1S/C19H15Cl2N3O2/c1-12-10-18(26-24-12)17(11-22-15-6-2-13(20)3-7-15)19(25)23-16-8-4-14(21)5-9-16/h2-11,22H,1H3,(H,23,25)/b17-11-

HIDE SMILES / InChI

Molecular Formula	C19H15Cl2N3O2
Molecular Weight	388.247
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: http://anvylllc.com/#/pipeline

AVL-3288 is a type I selective positive allosteric modulator of α7 nACHRs. It represents a "first-in-class" drug for the treatment of cognitive deficits in CNS disorders such as schizophrenia and potentially other diseases of cognitive impairment such as Alzheimer’s disease and ADHD. AVL-3288 was successfully tested in representative animal models of cognitive dysfunction in schizophrenia, a disease where α7 nAChR function is impaired. To date, no specific treatments for cognitive deficits in schizophrenia exist and approved therapies do not satisfactorily improve cognition. AVL-3288 is currently in human phase I trials.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neuronal acetylcholine receptor protein alpha-7 subunit 77 Target ID: CHEMBL2492 Sources: http://anvylllc.com/#/pipeline \| https://www.ncbi.nlm.nih.gov/pubmed/22804734	Positive Allosteric Modulator 179		500.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: https://clinicaltrials.gov/ct2/show/NCT02978599 http://adisinsight.springer.com/drugs/800038264 http://anvylllc.com/#/pipeline	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
239 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28196430	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	AVL-3288 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
79.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28196430	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	AVL-3288 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
310.73 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28196430	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	AVL-3288 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
1488 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28196430	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	AVL-3288 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
385 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28196430	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	AVL-3288 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4231 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28196430	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	AVL-3288 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.54 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28196430	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	AVL-3288 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28196430	3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered:	AVL-3288 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2.77 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28196430	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	AVL-3288 blood	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
30 mg single, oral Highest studied dose Dose: 30 mg Route: oral Route: single Dose: 30 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28196430 Page: p.5	healthy, 32 ± 9.9 n = 6 Health Status: healthy Age Group: 32 ± 9.9 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/28196430 Page: p.5	Sources: https://pubmed.ncbi.nlm.nih.gov/28196430 Page: p.5

Sourcing

Vendor/Aggregator	ID	URL
ApexBio Technology	B7511	https://www.apexbt.com/catalogsearch/result/?q=B7511
MolPort	MolPort-047-133-854	https://www.molport.com/shop/molecule-link/MolPort-047-133-854
Norris Pharm	NSZB-A197583
eMolecules	32234277	https://orderbb.emolecules.com/search/#?query=32234277

PubMed

Title	Date	PubMed
First in human trial of a type I positive allosteric modulator of alpha7-nicotinic acetylcholine receptors: Pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288.	2017 Apr	28196430
Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex.	2017 Mar 27	28131622

Patents

Sample Use Guides

In Vivo Use Guide

Treatment of schizophrenia: AVL-3288 10 or 30 mg daily for 5 days

Route of Administration: Oral

In Vitro Use Guide

AVL-3288 (0.1 nM to 10 uM) did not displace the binding of the selective a7 nAChR antagonist 125I-labeled a-bungarotoxin to rat brain tissue as quantified autoradiographically, nor did it directly evoke currents in oocytes expressing human a7 nAChRs. It evoked positive modulation of EC5 currents induced by acetylcholine (ACh), choline, and nicotine, with EC50 (and nH) values for positive modulation of 0.7 +/- 0.2 uM (1.4+/- 0.9), 0.6 +/- 0.1 uM (1.2+/-0.3), and 0.5 +/- 0.1 uM (1.2+/-0.3), respectively. A fixed concentration of AVL-3288 (1 uM) induced a leftward shift in the concentration–response curve for ACh, resulting in an 2.7-fold reduction in the EC50 values for ACh from 136 +/- 0.1 uM (control) to 50 +/- 0.1 uM (in the presence of compound AVL-3288) and a slight increase in nH values from 1.0 +/- 0.2 to 1.2 +/- 0.3, respectively

Substance Class	Chemical Created by `admin` on `Fri Dec 15 23:49:07 GMT 2023` Edited by `admin` on `Fri Dec 15 23:49:07 GMT 2023`
Record UNII	VA80VAX4WF
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

AVL-3288

Common Name

English

XY-4083

Code

English

UCI-4083

Code

English

(Z)-3-(4-CHLOROANILINO)-N-(4-CHLOROPHENYL)-2-(3-METHYLISOXAZOL-5-YL)PROP-2-ENAMIDE

Systematic Name

English

CCMI

Code

English

ANVYLIC-3288

Code

English

Code System Code Type Description

ChEMBL

CHEMBL429317

Created by admin on Fri Dec 15 23:49:07 GMT 2023 , Edited by admin on Fri Dec 15 23:49:07 GMT 2023

PRIMARY

FDA UNII

VA80VAX4WF

Created by admin on Fri Dec 15 23:49:07 GMT 2023 , Edited by admin on Fri Dec 15 23:49:07 GMT 2023

PRIMARY

PUBCHEM

16005981

Created by admin on Fri Dec 15 23:49:07 GMT 2023 , Edited by admin on Fri Dec 15 23:49:07 GMT 2023

PRIMARY

CAS

917837-54-8

Created by admin on Fri Dec 15 23:49:07 GMT 2023 , Edited by admin on Fri Dec 15 23:49:07 GMT 2023

PRIMARY

Details

SMILES

InChI

DescriptionSources: http://anvylllc.com/#/pipeline

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Cmax

AUC

T1/2

Doses

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: http://anvylllc.com/#/pipeline

C_max

T_1/2