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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 of AVL-3288

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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

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 TargetPharmacologyConditionPotency
500.0 nM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
239 ng/mL
10 mg single, oral
AVL-3288 blood
Homo sapiens
79.3 ng/mL
3 mg single, oral
AVL-3288 blood
Homo sapiens
310.73 ng/mL
30 mg single, oral
AVL-3288 blood
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
1488 ng × h/mL
10 mg single, oral
AVL-3288 blood
Homo sapiens
385 ng × h/mL
3 mg single, oral
AVL-3288 blood
Homo sapiens
4231 ng × h/mL
30 mg single, oral
AVL-3288 blood
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
1.54 h
10 mg single, oral
AVL-3288 blood
Homo sapiens
3.7 h
3 mg single, oral
AVL-3288 blood
Homo sapiens
2.77 h
30 mg single, oral
AVL-3288 blood
Homo sapiens

Doses

PubMed

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
Record UNII
VA80VAX4WF
Record Status Validated (UNII)
Record Version