Page last updated: 2024-10-15

bay 73-6691

Description

BAY 73-6691: potent and selective inhibitor of phosphodiesterase 9; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID135541419
SCHEMBL ID534220
MeSH IDM0493992

Synonyms (22)

Synonym
bay 73-6691, >=98% (hplc), powder
NCGC00165747-01
1-(2-chlorophenyl)-6-[(2r)-3,3,3-trifluoro-2-methylpropyl]-1,7-dihydro-4h-pyrazolo[3,4-d]pyrimidin-4-one
794568-92-6
bay 73-6691
1-(2-chlorophenyl)-6-[(2r)-3,3,3-trifluoro-2-methylpropyl]-1,5-dihydro-4h-pyrazolo[3,4-d]pyrimidine-4-one
(r)-bay-73-6691
80ztv3intw ,
4h-pyrazolo(3,4-d)pyrimidin-4-one, 1-(2-chlorophenyl)-1,5-dihydro-6-((2r)-3,3,3-trifluoro-2-methylpropyl)-
unii-80ztv3intw
bay-73-6691
SCHEMBL534220
wdjdffufzopsja-mrvpvssysa-n
BCP20762
CS-0025654
HY-104028
MS-25592
1-(2-chlorophenyl)-6-[(2r)-3,3,3-trifluoro-2-methylpropyl]-5h-pyrazolo[3,4-d]pyrimidin-4-one
ffpxpxoafqcnbs-mrvpvssysa-n
1-(2-chlorophenyl)-1,5-dihydro-6-((2r)-3,3,3-trifluoro-2-methylpropyl)-4h-pyrazolo(3,4-d)pyrimidin-4-one
DTXSID501028165
AKOS040732551

Bioavailability

ExcerptReference
" The results of this study are original and demonstrate that inhibition of phosphodiesterase-9 in neutrophils from SCA patients with BAY 73-6691 was able to increase the NO bioavailability and attenuate oxidative stress and inflammation in neutrophils from patients not treated with HU."( The Effect of a Selective Inhibitor of Phosphodiesterase-9 on Oxidative Stress, Inflammation and Cytotoxicity in Neutrophils from Patients with Sickle Cell Anaemia.
Barbosa, MC; de Araújo Lopes, A; de Jesus dos Santos, TE; dos Santos, TN; Elias, DB; Gonçalves Lemes, RP; Leal, LK; Pedrosa, AM; Sasahara, GL, 2016
)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (4)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
vitamin D3 receptor isoform VDRAHomo sapiens (human)Potency89.12510.354828.065989.1251AID504847
thyroid hormone receptor beta isoform aHomo sapiens (human)Potency125.89200.010039.53711,122.0200AID1479
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)IC50 (µMol)0.04220.00801.16175.6000AID1175918; AID1175919; AID1625391
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)IC50 (µMol)0.05000.00002.14179.2000AID1587244
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (15)

Processvia Protein(s)Taxonomy
signal transductionHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
positive regulation of cardiac muscle hypertrophyHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
cGMP metabolic processHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
cGMP catabolic processHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
positive regulation of long-term synaptic potentiationHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
negative regulation of neural precursor cell proliferationHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
cAMP-mediated signalingHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
response to amphetamineCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
locomotory behaviorCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
visual learningCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
monocyte differentiationCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
cellular response to macrophage colony-stimulating factor stimulusCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
dopamine catabolic processCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
serotonin metabolic processCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
cellular response to granulocyte macrophage colony-stimulating factor stimulusCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
cAMP-mediated signalingCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (8)

Processvia Protein(s)Taxonomy
3',5'-cyclic-nucleotide phosphodiesterase activityHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
protein bindingHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
metal ion bindingHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
3',5'-cyclic-GMP phosphodiesterase activityHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
3',5'-cyclic-AMP phosphodiesterase activityHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
3',5'-cyclic-AMP phosphodiesterase activityCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
calmodulin-activated dual specificity 3',5'-cyclic-GMP, 3',5'-cyclic-AMP phosphodiesterase activityCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
protein bindingCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
calmodulin bindingCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
metal ion bindingCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
3',5'-cyclic-GMP phosphodiesterase activityCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
calmodulin-activated 3',5'-cyclic-GMP phosphodiesterase activityCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (10)

Processvia Protein(s)Taxonomy
nucleoplasmHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
endoplasmic reticulumHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
Golgi apparatusHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
cytosolHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
plasma membraneHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
ruffle membraneHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
sarcolemmaHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
perikaryonHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
perinuclear region of cytoplasmHigh affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9AHomo sapiens (human)
cytosolCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
neuronal cell bodyCalcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1BHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (8)

Assay IDTitleYearJournalArticle
AID1596284Inhibition of recombinant N-terminal GST-tagged full length human PDE9A2 expressed in Sf9 cells using F AM-cGMP as substrate at 0.1xIC50 incubated for 60 mins by fluorescence plate reader analysis2019European journal of medicinal chemistry, Jul-15, Volume: 174InCl
AID1587244Inhibition of PDE1B catalytic domain (10 to 487 residues) (unknown origin) using 3H-cGMP as substrate after 15 mins by liquid scintillation counting method2019Journal of medicinal chemistry, 04-25, Volume: 62, Issue:8
Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia.
AID1596328Inhibition of recombinant N-terminal GST-tagged full length human PDE9A2 expressed in Sf9 cells using F AM-cGMP as substrate at 10xIC50 incubated for 60 mins by fluorescence plate reader analysis2019European journal of medicinal chemistry, Jul-15, Volume: 174InCl
AID1625391Inhibition of recombinant human PDE9A2 catalytic domain (181 to 506 residues) expressed in Escherichia coli BL21-CodonPlus cells using [3H]cGMP or [3H]cAMP as substrate incubated for 15 mins by liquid scintillation counting method2016Journal of medicinal chemistry, Aug-11, Volume: 59, Issue:15
PDEStrIAn: A Phosphodiesterase Structure and Ligand Interaction Annotated Database As a Tool for Structure-Based Drug Design.
AID464254Inhibition of PDE92010Journal of medicinal chemistry, Feb-25, Volume: 53, Issue:4
Insight into binding of phosphodiesterase-9A selective inhibitors by crystal structures and mutagenesis.
AID1175919Inhibition of human PDE9A2 using [3H]cGMP as substrate by scintillation proximity assay2014Journal of natural products, Dec-26, Volume: 77, Issue:12
(±)-Torreyunlignans A-D, rare 8-9' linked neolignan enantiomers as phosphodiesterase-9A inhibitors from Torreya yunnanensis.
AID1596306Inhibition of recombinant N-terminal GST-tagged full length human PDE9A2 expressed in Sf9 cells using F AM-cGMP as substrate at 1xIC50 incubated for 60 mins by fluorescence plate reader analysis2019European journal of medicinal chemistry, Jul-15, Volume: 174InCl
AID1175918Inhibition of recombinant PDE9A2 catalytic domain (unknown origin) expressed in Escherichia coli BL21 using [3H]cGMP as substrate after 15 mins by liquid scintillation counting analysis2014Journal of natural products, Dec-26, Volume: 77, Issue:12
(±)-Torreyunlignans A-D, rare 8-9' linked neolignan enantiomers as phosphodiesterase-9A inhibitors from Torreya yunnanensis.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (19)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's2 (10.53)29.6817
2010's16 (84.21)24.3611
2020's1 (5.26)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other20 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]