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Details

Stereochemistry RACEMIC
Molecular Formula C22H21N3O3S
Molecular Weight 407.485
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ANA-12

SMILES

O=C(NC1=C(C=CC=C1)C(=O)NC2CCCCNC2=O)C3=CC4=CC=CC=C4S3

InChI

InChIKey=TUSCYCAIGRVBMD-UHFFFAOYSA-N
InChI=1S/C22H21N3O3S/c26-20(25-17-10-5-6-12-23-21(17)27)15-8-2-3-9-16(15)24-22(28)19-13-14-7-1-4-11-18(14)29-19/h1-4,7-9,11,13,17H,5-6,10,12H2,(H,23,27)(H,24,28)(H,25,26)

HIDE SMILES / InChI

Molecular Formula C22H21N3O3S
Molecular Weight 407.485
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

ANA-12 is a low-molecular weight antagonist of tropomyosin-related kinase B (TrkB), which is the main receptor of neurotrophin brain-derived neurotrophic factor (BDNF). TrkB and BDNF are both the key mediators in the pathophysiology of several mood disorders, including anxiety and depression. ANA-12 showed direct and selective binding to TrkB and inhibited processes downstream of TrkB without altering TrkA and TrkC functions. It was shown, that mice administered ANA-12 demonstrated reduced anxiety- and depression-related behaviors on a variety of tests predictive of anxiolytic and antidepressant properties in humans.

CNS Activity

Curator's Comment: Known to be CNS penetrant in mouse. Human data not available.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
12.0 µM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice.
2011 May
Physical exercise and environment exploration affect synaptogenesis in adult-generated neurons in the rat dentate gyrus: possible role of BDNF.
2013 Oct 9
BDNF-TrkB signaling in the nucleus accumbens shell of mice has key role in methamphetamine withdrawal symptoms.
2015 Oct 27

Sample Use Guides

F1 hybrids obtained by crossing C57BL/6 and 129SveV mice were used: a volume of 10 μl/g body weight was injected i.p. for saline and ANA-12 (0.5 mg/kg body weight) solutions.
Route of Administration: Intraperitoneal
ANA-12 directly binds and selectively modulates TrkB. Bodipy–ANA-12 (100 μM) was incubated with increasing amounts of TrkBECD-Fc, IgG-Fc, BSA, or nothing. At concentrations up to 10–100 μM, ANA-12 completely abolished the effects of BDNF since no single neurite or branching could be observed even after 3 days of incubation. To assess the selectivity of the compound toward TrkB, there were used 2 other nnr5-PC12 cell lines expressing either TrkA or TrkC for which neurite outgrowth is dependent on NGF and NT-3, respectively. In these cell lines, ANA-12 had no effect on neurite outgrowth. Three days incubation with concentrations as high as 100 μM of ANA-12 did not affect NGF- and NT-3–dependent neurite length and branching, confirming its specificity to TrkB-related signaling.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:59:48 GMT 2023
Edited
by admin
on Sat Dec 16 16:59:48 GMT 2023
Record UNII
54S4JPT8JX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ANA-12
Common Name English
BENZO(B)THIOPHENE-2-CARBOXAMIDE, N-(2-(((HEXAHYDRO-2-OXO-1H-AZEPIN-3-YL)AMINO)CARBONYL)PHENYL)-
Systematic Name English
N-(2-(((HEXAHYDRO-2-OXO-1H-AZEPIN-3-YL)AMINO)CARBONYL)PHENYL)BENZO(B)THIOPHENE-2-CARBOXAMIDE
Systematic Name English
Code System Code Type Description
FDA UNII
54S4JPT8JX
Created by admin on Sat Dec 16 16:59:48 GMT 2023 , Edited by admin on Sat Dec 16 16:59:48 GMT 2023
PRIMARY
EPA CompTox
DTXSID501045818
Created by admin on Sat Dec 16 16:59:48 GMT 2023 , Edited by admin on Sat Dec 16 16:59:48 GMT 2023
PRIMARY
WIKIPEDIA
ANA-12
Created by admin on Sat Dec 16 16:59:48 GMT 2023 , Edited by admin on Sat Dec 16 16:59:48 GMT 2023
PRIMARY
CAS
219766-25-3
Created by admin on Sat Dec 16 16:59:48 GMT 2023 , Edited by admin on Sat Dec 16 16:59:48 GMT 2023
PRIMARY
PUBCHEM
2799722
Created by admin on Sat Dec 16 16:59:48 GMT 2023 , Edited by admin on Sat Dec 16 16:59:48 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
ANTAGONIST