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
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-
DescriptionSources: http://anvylllc.com/#/pipeline
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
Cmax
| Value | Dose | Co-administered | 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 | Co-administered | 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 |
T1/2
| Value | Dose | Co-administered | 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 |
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 |
|
| Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex. | 2017 Mar 27 |
Patents
Sample Use Guides
Treatment of schizophrenia: AVL-3288 10 or 30 mg daily for 5 days
Route of Administration:
Oral
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
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CHEMBL429317
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VA80VAX4WF
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16005981
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917837-54-8
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SUBSTANCE RECORD
