Page last updated: 2024-11-13

tak-063

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

1-(2-fluoro-4-(1H-pyrazol-1-yl)phenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one: an inhibitor of phosphodiesterase 10A; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID46848915
CHEMBL ID3989972
SCHEMBL ID518714
MeSH IDM000601779

Synonyms (43)

Synonym
KVHRYLNQDWXAGI-UHFFFAOYSA-N
S8459
3k9 ,
1-[2-fluoro-4-(1h-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1h-pyrazol-5-yl)pyridazin-4(1h)-one
SCHEMBL518714
CS-3551
balipodect
HY-12472
AC-32915
tak 063
1-(2-fluoro-4-(1h-pyrazol-1-yl)phenyl)-5-methoxy-3-(1-phenyl-1h-pyrazol-5-yl)pyridazin-4(1h)-one
1238697-26-1
tak063
TAK-063 ,
3WYM
J-690093
AKOS026750192
EX-A568
balipodect [usan:inn:who-dd]
unii-6650w303h0
balipodect [inn]
1-[2-fluoro-4-(1h-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1h-pyrazol-5-yl)-1,4-dihydropyridazin-4-one
balipodect [who-dd]
6650W303H0 ,
4(1h)-pyridazinone, 1-(2-fluoro-4-(1h-pyrazol-1-yl)phenyl)-5-methoxy-3-(1-phenyl-1h-pyrazol-5-yl)-
balipodect [usan]
1-(2-fluoro-4-(1h-pyrazol-1-yl)phenyl)-5-methoxy- 3-(1-phenyl-1h-pyrazol-5-yl)pyridazin-4(1h)-one
mfcd28385852
NCGC00390654-01
1-(2-fluoro-4-pyrazol-1-ylphenyl)-5-methoxy-3-(2-phenylpyrazol-3-yl)pyridazin-4-one
FT-0700141
DB14774
BS-15045
c23h17fn6o2
CHEMBL3989972
BCP14040
balipodect (usan/inn)
D11245
SB17000
HMS3886P10
CCG-268978
Q27453873
A857435

Research Excerpts

Toxicity

TAK-063 was safe and well tolerated at doses up to 1000 mg. Most adverse events were mild or moderate in severity and did not result in discontinuation.

ExcerptReferenceRelevance
"The most common drug-related adverse events (AEs) were somnolence (33."( A phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-063, a selective PDE10A inhibitor.
Chrones, L; Gevorkyan, H; Macek, TA; Tsai, M; Xie, J, 2016
)
0.66
"TAK-063 was safe and well tolerated at doses up to 1000 mg and demonstrated a pharmacokinetic profile supporting once-daily dosing."( A phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-063, a selective PDE10A inhibitor.
Chrones, L; Gevorkyan, H; Macek, TA; Tsai, M; Xie, J, 2016
)
2.1
"Multiple doses of TAK-063 were safe and well tolerated."( A Randomized Multiple Dose Pharmacokinetic Study of a Novel PDE10A Inhibitor TAK-063 in Subjects with Stable Schizophrenia and Japanese Subjects and Modeling of Exposure Relationships to Adverse Events.
Affinito, J; Gertsik, L; Goldsmith, P; Macek, TA; McCue, M; Roepcke, S; Tsai, M; Xie, J, 2017
)
1.02
" Consistent with previous phase 1 studies, TAK-063 was safe and well tolerated, and most adverse events were mild or moderate in severity and did not result in discontinuation."( A phase 2, randomized, placebo-controlled study of the efficacy and safety of TAK-063 in subjects with an acute exacerbation of schizophrenia.
Affinito, J; Dong, X; Goldsmith, P; Hanson, E; Macek, TA; Mahableshwarkar, AR; McCue, M, 2019
)
1

Pharmacokinetics

ExcerptReferenceRelevance
"TAK-063 was safe and well tolerated at doses up to 1000 mg and demonstrated a pharmacokinetic profile supporting once-daily dosing."( A phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-063, a selective PDE10A inhibitor.
Chrones, L; Gevorkyan, H; Macek, TA; Tsai, M; Xie, J, 2016
)
2.1

Bioavailability

ExcerptReferenceRelevance
"3 mg/kg, bioavailability of TAK-063 was 27."( Pre-clinical Characterization of Absorption, Distribution, Metabolism and Excretion Properties of TAK-063.
Kato, S; Morohashi, A; Sudo, M; Tagawa, Y; Takahashi, J; Tohyama, K, 2018
)
0.99
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (7)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency26.83700.01237.983543.2770AID1645841
GVesicular stomatitis virusPotency15.09160.01238.964839.8107AID1645842
cytochrome P450 2D6Homo sapiens (human)Potency26.83700.00108.379861.1304AID1645840
Interferon betaHomo sapiens (human)Potency15.09160.00339.158239.8107AID1645842
HLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)Potency15.09160.01238.964839.8107AID1645842
Inositol hexakisphosphate kinase 1Homo sapiens (human)Potency15.09160.01238.964839.8107AID1645842
cytochrome P450 2C9, partialHomo sapiens (human)Potency15.09160.01238.964839.8107AID1645842
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (45)

Processvia Protein(s)Taxonomy
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell activation involved in immune responseInterferon betaHomo sapiens (human)
cell surface receptor signaling pathwayInterferon betaHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to virusInterferon betaHomo sapiens (human)
positive regulation of autophagyInterferon betaHomo sapiens (human)
cytokine-mediated signaling pathwayInterferon betaHomo sapiens (human)
natural killer cell activationInterferon betaHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT proteinInterferon betaHomo sapiens (human)
cellular response to interferon-betaInterferon betaHomo sapiens (human)
B cell proliferationInterferon betaHomo sapiens (human)
negative regulation of viral genome replicationInterferon betaHomo sapiens (human)
innate immune responseInterferon betaHomo sapiens (human)
positive regulation of innate immune responseInterferon betaHomo sapiens (human)
regulation of MHC class I biosynthetic processInterferon betaHomo sapiens (human)
negative regulation of T cell differentiationInterferon betaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIInterferon betaHomo sapiens (human)
defense response to virusInterferon betaHomo sapiens (human)
type I interferon-mediated signaling pathwayInterferon betaHomo sapiens (human)
neuron cellular homeostasisInterferon betaHomo sapiens (human)
cellular response to exogenous dsRNAInterferon betaHomo sapiens (human)
cellular response to virusInterferon betaHomo sapiens (human)
negative regulation of Lewy body formationInterferon betaHomo sapiens (human)
negative regulation of T-helper 2 cell cytokine productionInterferon betaHomo sapiens (human)
positive regulation of apoptotic signaling pathwayInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell differentiationInterferon betaHomo sapiens (human)
natural killer cell activation involved in immune responseInterferon betaHomo sapiens (human)
adaptive immune responseInterferon betaHomo sapiens (human)
T cell activation involved in immune responseInterferon betaHomo sapiens (human)
humoral immune responseInterferon betaHomo sapiens (human)
positive regulation of T cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
adaptive immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independentHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of T cell anergyHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
defense responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
detection of bacteriumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-12 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-6 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protection from natural killer cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
innate immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of dendritic cell differentiationHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class IbHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
inositol phosphate metabolic processInositol hexakisphosphate kinase 1Homo sapiens (human)
phosphatidylinositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
negative regulation of cold-induced thermogenesisInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (18)

Processvia Protein(s)Taxonomy
cytokine activityInterferon betaHomo sapiens (human)
cytokine receptor bindingInterferon betaHomo sapiens (human)
type I interferon receptor bindingInterferon betaHomo sapiens (human)
protein bindingInterferon betaHomo sapiens (human)
chloramphenicol O-acetyltransferase activityInterferon betaHomo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
signaling receptor bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
peptide antigen bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein-folding chaperone bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
inositol-1,3,4,5,6-pentakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol heptakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
protein bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
ATP bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 1-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 3-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol 5-diphosphate pentakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol diphosphate tetrakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (22)

Processvia Protein(s)Taxonomy
extracellular spaceInterferon betaHomo sapiens (human)
extracellular regionInterferon betaHomo sapiens (human)
Golgi membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
endoplasmic reticulumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
Golgi apparatusHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
cell surfaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
ER to Golgi transport vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
secretory granule membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
phagocytic vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
early endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
recycling endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular exosomeHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
lumenal side of endoplasmic reticulum membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
MHC class I protein complexHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular spaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
external side of plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
fibrillar centerInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
cytosolInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleusInositol hexakisphosphate kinase 1Homo sapiens (human)
cytoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (5)

Assay IDTitleYearJournalArticle
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (24)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's18 (75.00)24.3611
2020's6 (25.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 21.72

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index21.72 (24.57)
Research Supply Index3.40 (2.92)
Research Growth Index4.54 (4.65)
Search Engine Demand Index21.17 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (21.72)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials5 (20.83%)5.53%
Reviews1 (4.17%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other18 (75.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]