GUVACINE (PD004523, QTDZOWFRBNTPQR-UHFFFAOYSA-N)

General

Preferred name

GUVACINE

Synonyms

GUVACINE HYDROCHLORIDE

4-substituted 2,4-dioxobutanoic acids

Guvacine HCl

Guvacine (hydrochloride)

P&D ID

PD004523

CAS

6027-91-4

51884-11-8

498-96-4

Tags

available

natural product

drug candidate

Drug indication

Discovery agent

Drug Status

experimental

Structure

PD004523

GUVACINE

RO5

127.06

HBA

HBD

LOGP

-0.01

Structure formats

SMILES

O=C(O)C1=CCCNC1

InChI

InChI=1S/C6H9NO2/c8-6(9)5-2-1-3-7-4-5/h2,7H,1,3-4H2,(H,8,9)

InChIkey

QTDZOWFRBNTPQR-UHFFFAOYSA-N

MOL

GUVACINE RDKit 2D 9 9 0 0 0 0 0 0 0 0999 V2000 3.7500 -1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7500 1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 4 1 0 M END > <ID> PD004523 > <Name> GUVACINE

Description

(extracted from source data)

DESCRIPTION A pyridine alkaloid found in the Areca nut. (GtoPdb)

DESCRIPTION GABA uptake inhibitor (LOPAC library)

DESCRIPTION Specific GABA uptake inhibitor (Tocriscreen Total)

DESCRIPTION Guvacine hydrochloride is a specific GABA uptake inhibitor (IC50 = 14, 58, 119 and 1870 μM for hGAT-1, rGAT-2, hGAT-3 and hBGT-1, respectively). Guvacine may be beneficial for the treatment of neuropsychiatric disorders. (BOC Sciences Bioactive Compounds)

Protein targets

7.3

BLM RecQ-like DNA helicase BLM

BIOCHEM 281.8x

4.85

SLC6A1 Sodium- and chloride-dependent GABA transporter 1 inhibitor

CELL-BASED 7.1x

4.59

SLC6A11 Sodium- and chloride-dependent GABA transporter 3 inhibitor

4.4

TSHR Thyrotropin receptor

4.18

4.36

SLC6A13 Sodium- and chloride-dependent GABA transporter 2 inhibitor

SLC6A12 Sodium- and chloride-dependent betaine transporter inhibitor

Target pathways

Amino acid transport across the plasma membrane

R-HSA-352230

SLC6A12

Creatine metabolism

R-HSA-71288

SLC6A11

SLC6A12

Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function

R-HSA-9704331

BLM

Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function

R-HSA-9704646

BLM

Defective homologous recombination repair (HRR) due to BRCA1 loss of function

R-HSA-9701192

BLM

G alpha (s) signalling events

R-HSA-418555

TSHR

G2/M DNA damage checkpoint

R-HSA-69473

BLM

HDR through Homologous Recombination (HRR)

R-HSA-5685942

BLM

HDR through Single Strand Annealing (SSA)

R-HSA-5685938

BLM

Homologous DNA Pairing and Strand Exchange

R-HSA-5693579

BLM

Hormone ligand-binding receptors

R-HSA-375281

TSHR

Impaired BRCA2 binding to PALB2

R-HSA-9709603

BLM

Impaired BRCA2 binding to RAD51

R-HSA-9709570

BLM

Meiotic recombination

R-HSA-912446

BLM

Na+/Cl- dependent neurotransmitter transporters

R-HSA-442660

SLC6A13

SLC6A11

SLC6A12

SLC6A1

Presynaptic phase of homologous DNA pairing and strand exchange

R-HSA-5693616

BLM

Processing of DNA double-strand break ends

R-HSA-5693607

BLM

Processive synthesis on the C-strand of the telomere

R-HSA-174414

BLM

Regulation of TP53 Activity through Phosphorylation

R-HSA-6804756

BLM

Resolution of D-loop Structures through Holliday Junction Intermediates

R-HSA-5693568

BLM

Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)

R-HSA-5693554

BLM

Reuptake of GABA

R-HSA-888593

SLC6A13

SLC6A11

SLC6A12

SLC6A1

SUMOylation of DNA damage response and repair proteins

R-HSA-3108214

BLM

References

2019 Screening oxime libraries by means of mass spectrometry (MS) binding assays: Identification of new highly potent inhibitors to optimized inhibitors γ-aminobutyric acid transporter 1.

Kern F, Wanner KT. Bioorg Med Chem

2016 Straightforward and effective synthesis of -aminobutyric acid transporter subtype 2-selective acyl-substituted azaspiro[4.5]decanes.

Ma X, Lubin H et al. Bioorg. Med. Chem. Lett.

2013 Focused pseudostatic hydrazone libraries screened by mass spectrometry binding assay: optimizing affinities toward γ-aminobutyric acid transporter 1.

Sindelar M; Lutz TA et al.

2010 Azetidine derivatives as novel gamma-aminobutyric acid uptake inhibitors: synthesis, biological evaluation, and structure-activity relationship.

Faust MR, Hofner G et al. Eur. J. Med. Chem.

2008 Synthesis and biological evaluation of aminomethylphenol derivatives as inhibitors of the murine GABA transporters mGAT1-mGAT4.

Kragler A, Hofner G et al. Eur. J. Med. Chem.

2004 Novel secoergoline derivatives inhibit both GABA and glutamate uptake in rat brain homogenates: synthesis, in vitro pharmacology, and modeling.

Héja L; Kovács I et al.

1999 Selective inhibitors of glial GABA uptake: synthesis, absolute stereochemistry, and pharmacology of the enantiomers of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole (exo-THPO) and analogues.

Falch E, Perregaard J et al. J. Med. Chem.

1994 Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3.

Dhar TG; Borden LA et al.

1992 Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake.

Pavia MR, Lobbestael SJ et al. J. Med. Chem.

1985 Orally active and potent inhibitors of gamma-aminobutyric acid uptake.

Ali FE, Bondinell WE et al. J. Med. Chem.

PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors and Activators of N370S glucocerebrosidase as a Potential Chaperone Treatment of Gaucher Disease: Purified N370S Glucocerebrosidase. (Class of assay: confirmatory) [Related pubchem assays: 2101 ] AID 2597

AID 602473