Page last updated: 2024-12-11

tak 475

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

Description

1-((1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl)acetyl)piperidine-4-acetic acid: inhibits squalene synthase; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9874248
CHEMBL ID435224
SCHEMBL ID206424
MeSH IDM0440124

Synonyms (32)

Synonym
lapaquistat acetate (jan/usan)
189060-13-7
D06609
2-(1-(2-((3r,5s)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3- dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydrobenzo(e)(1,4)oxazepin-3- yl)acetyl)piperidin-4-yl)acetic acid
4-piperidineacetic acid, 1-(((3r,5s)-1-(3-(acetyloxy)-2,2-dimethylpropyl)-7- chloro-5-(2,3-dimethoxyphenyl)-1,2,3,5-tetrahydro-2-oxo-4,1-benzoxazepin-3- yl)acetyl)-
lapaquistat acetate [usan]
tak 475
lapaquistat acetate
tak-475
CHEMBL435224 ,
bdbm50118897
(1-{2-[1-(3-acetoxy-2,2-dimethyl-propyl)-7-chloro-5-(2,3-dimethoxy-phenyl)-2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]oxazepin-3-yl]-acetyl}-piperidin-4-yl)-acetic acid
lapaquistat acetate [usan:jan]
unii-iuh3ay74o3
iuh3ay74o3 ,
1-((1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl)acetyl)piperidine-4-acetic acid
4-piperidineacetic acid, 1-(((3r,5s)-1-(3-(acetyloxy)-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-1,2,3,5-tetrahydro-2-oxo-4,1-benzoxazepin-3-yl)acetyl)-
2-(1-(2-((3r,5s)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3- dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydrobenzo(e)(1,4)oxazepin-3-yl)acetyl)piperidin-4-yl)acetic acid
lapaquistat acetate [jan]
SCHEMBL206424
2-(1-(2-((3r,5s)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydrobenzo[e][1,4]oxazepin-3-yl)acetyl)piperidin-4-yl)acetic acid
DTXSID50432130
AKOS027326614
J-012187
lapaquistat acetate (tak-475)
2-[1-[2-[(3r,5s)-1-(3-acetyloxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-5h-4,1-benzoxazepin-3-yl]acetyl]piperidin-4-yl]acetic acid
t-91485
Q27280898
CS-0006278
HY-16274
EX-A5978
2-(1-{2-[(3r,5s)-1-[3-(acetyloxy)-2,2-dimethylpropyl]-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl}piperidin-4-yl)acetic acid

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" These pharmacokinetic characteristics in animals were also confirmed in the clinical studies."( Pharmacokinetics of TAK-475, a Squalene Synthase Inhibitor, in Rats and Dogs.
Asahi, S; Ebihara, T; Kondo, T; Moriwaki, T; Tagawa, Y; Teshima, K, 2016
)
0.43

Dosage Studied

ExcerptRelevanceReference
" Preclinical pharmacokinetic studies have demonstrated that most of the dosed TAK-475 was hydrolyzed to M-I during the absorption process and the concentrations of M-I in the liver, the main organ of cholesterol biosynthesis, were much higher than those in the plasma after oral administration to rats."( Characterization of Transporters in the Hepatic Uptake of TAK-475 M-I, a Squalene Synthase Inhibitor, in Rats and Humans.
Asahi, S; Ebihara, T; Kondo, T; Moriwaki, T; Moriya, Y; Tagawa, Y; Takeuchi, T, 2016
)
0.43
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Squalene synthaseHomo sapiens (human)IC50 (µMol)0.14550.07802.14788.0000AID227678; AID598881
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (3)

Processvia Protein(s)Taxonomy
steroid biosynthetic processSqualene synthaseHomo sapiens (human)
farnesyl diphosphate metabolic processSqualene synthaseHomo sapiens (human)
cholesterol biosynthetic processSqualene synthaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (5)

Processvia Protein(s)Taxonomy
farnesyltranstransferase activitySqualene synthaseHomo sapiens (human)
protein bindingSqualene synthaseHomo sapiens (human)
metal ion bindingSqualene synthaseHomo sapiens (human)
farnesyl-diphosphate farnesyltransferase activitySqualene synthaseHomo sapiens (human)
squalene synthase activitySqualene synthaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (3)

Processvia Protein(s)Taxonomy
endoplasmic reticulumSqualene synthaseHomo sapiens (human)
endoplasmic reticulum membraneSqualene synthaseHomo sapiens (human)
membraneSqualene synthaseHomo sapiens (human)
endoplasmic reticulum membraneSqualene synthaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (21)

Assay IDTitleYearJournalArticle
AID1515594Antioxidant activity in rat hepatic microsomes assessed as reduction in ferrous salt/ascorbic acid-induced lipid peroxidation of membrane lipids by measuring TBARS level after 45 mins by spectrophotometric method2019ACS medicinal chemistry letters, Jan-10, Volume: 10, Issue:1
Optimizing the Pharmacological Profile of New Bifunctional Antihyperlipidemic/Antioxidant Morpholine Derivatives.
AID598881Inhibition of recombinant squalene synthase assessed as conversion of trans,trans-[1-3H]farnesyl pyrophosphate to [3H]squalene after 10 mins by liquid scintillation counting2011Bioorganic & medicinal chemistry letters, Jun-15, Volume: 21, Issue:12
Identification of 4H,6H-[2]benzoxepino[4,5-c][1,2]oxazoles as novel squalene synthase inhibitors.
AID598883In vivo inhibition of squalene synthase in NMRI rat assessed as inhibition of hepatic [14C]cholesterol biosynthesis at 3 mg/kg, po measured after 1 hr by liquid scintillation counting2011Bioorganic & medicinal chemistry letters, Jun-15, Volume: 21, Issue:12
Identification of 4H,6H-[2]benzoxepino[4,5-c][1,2]oxazoles as novel squalene synthase inhibitors.
AID777272Reduction in triglyceride level in marmosets at 30 mg/kg/day, po for 7 days2013ACS medicinal chemistry letters, Oct-10, Volume: 4, Issue:10
Discovery of DF-461, a Potent Squalene Synthase Inhibitor.
AID672687Lipid lowering effect in marmosets assessed as reduction in plasma non HDL-cholesterol level at 100 mg/kg, po administered once daily for 7 days2012Bioorganic & medicinal chemistry, May-01, Volume: 20, Issue:9
Discovery of novel tricyclic compounds as squalene synthase inhibitors.
AID777273Reduction in HDL cholesterol level in marmosets at 30 mg/kg/day, po for 7 days2013ACS medicinal chemistry letters, Oct-10, Volume: 4, Issue:10
Discovery of DF-461, a Potent Squalene Synthase Inhibitor.
AID672688Lipid lowering effect in marmosets assessed as reduction in plasma triglyceride level at 100 mg/kg, po administered once daily for 7 days2012Bioorganic & medicinal chemistry, May-01, Volume: 20, Issue:9
Discovery of novel tricyclic compounds as squalene synthase inhibitors.
AID1515597Inhibition of SQS in rat liver microsomes assessed as reduction in [3H]FPP conversion to squalene after 45 mins by liquid scintillation counting method2019ACS medicinal chemistry letters, Jan-10, Volume: 10, Issue:1
Optimizing the Pharmacological Profile of New Bifunctional Antihyperlipidemic/Antioxidant Morpholine Derivatives.
AID777269Inhibition of cholesterol synthesis in po dosed Wistar rat administered as single dose prior to [14C]mevalonolactone injection measured after 7 hrs by liquid scintillation counting2013ACS medicinal chemistry letters, Oct-10, Volume: 4, Issue:10
Discovery of DF-461, a Potent Squalene Synthase Inhibitor.
AID1656768Induction of human HMGCR-dCat-ELuc degradation expressed in HEK293 cells assessed as reduction in luciferase activity after 8 hrs by luciferase reporter assay2020Bioorganic & medicinal chemistry, 02-01, Volume: 28, Issue:3
Luciferase-based HMG-CoA reductase degradation assay for activity and selectivity profiling of oxy(lano)sterols.
AID219411Compound at a dose of 1 mg/kg was administered orally to 6 week old male Wistar rats and was evaluated for the inhibition of sterol synthesis2002Journal of medicinal chemistry, Sep-26, Volume: 45, Issue:20
Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis.
AID598882Stability in human liver microsomes assessed as compound remaining after 60 mins2011Bioorganic & medicinal chemistry letters, Jun-15, Volume: 21, Issue:12
Identification of 4H,6H-[2]benzoxepino[4,5-c][1,2]oxazoles as novel squalene synthase inhibitors.
AID672686Lipid lowering effect in marmosets assessed as reduction in plasma HDL-cholesterol level at 100 mg/kg, po administered once daily for 7 days2012Bioorganic & medicinal chemistry, May-01, Volume: 20, Issue:9
Discovery of novel tricyclic compounds as squalene synthase inhibitors.
AID227678Inhibition of squalene synthase from human hepatoma cells (HepG2)2002Journal of medicinal chemistry, Sep-26, Volume: 45, Issue:20
Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis.
AID219414Compound at a dose of 3 mg/kg was dministered orally to 6 week old male Wistar rats and was evaluated for the inhibition of terol synthesis2002Journal of medicinal chemistry, Sep-26, Volume: 45, Issue:20
Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis.
AID777275Reduction in total cholesterol level in marmosets at 30 mg/kg/day, po for 7 days2013ACS medicinal chemistry letters, Oct-10, Volume: 4, Issue:10
Discovery of DF-461, a Potent Squalene Synthase Inhibitor.
AID777274Reduction in non-HDL cholesterol level in marmosets at 30 mg/kg/day, po for 7 days2013ACS medicinal chemistry letters, Oct-10, Volume: 4, Issue:10
Discovery of DF-461, a Potent Squalene Synthase Inhibitor.
AID219271Concentration required for 50% inhibitory activity against cholesterol synthesis in rat liver2002Journal of medicinal chemistry, Sep-26, Volume: 45, Issue:20
Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis.
AID598884In vivo inhibition of squalene synthase in NMRI rat assessed as inhibition of hepatic [14C]cholesterol biosynthesis at 1 mg/kg, po measured after 1 hr by liquid scintillation counting2011Bioorganic & medicinal chemistry letters, Jun-15, Volume: 21, Issue:12
Identification of 4H,6H-[2]benzoxepino[4,5-c][1,2]oxazoles as novel squalene synthase inhibitors.
AID219412In vivo inhibition of sterol synthesis in rats following 10 mg/kg p.o.2002Journal of medicinal chemistry, Sep-26, Volume: 45, Issue:20
Synthesis of novel 4,1-benzoxazepine derivatives as squalene synthase inhibitors and their inhibition of cholesterol synthesis.
AID672685Lipid lowering effect in marmosets assessed as reduction in plasma total cholesterol level at 100 mg/kg, po administered once daily for 7 days2012Bioorganic & medicinal chemistry, May-01, Volume: 20, Issue:9
Discovery of novel tricyclic compounds as squalene synthase inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (22)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's10 (45.45)29.6817
2010's10 (45.45)24.3611
2020's2 (9.09)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 18.97

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 Index18.97 (24.57)
Research Supply Index3.18 (2.92)
Research Growth Index4.52 (4.65)
Search Engine Demand Index15.26 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (18.97)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews6 (26.09%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other17 (73.91%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]