Page last updated: 2024-12-08

sk&f 99085

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

Cross-References

ID SourceID
PubMed CID176405
CHEMBL ID4639024
SCHEMBL ID1648488
MeSH IDM0303804

Synonyms (26)

Synonym
sr-9223i
apomine
sk&f-99085
sr-45023a
4-[2,2-bis[di(propan-2-yloxy)phosphoryl]ethyl]-2,6-ditert-butylphenol
unii-jq95208805
apb-231-a2
jq95208805 ,
phosphonic acid, (2-(3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl)ethylidene)bis-, tetrakis(1-methylethyl) ester
skf 99085
sr 9223i
sr 45023a
126411-13-0
tetraisopropyl 2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethyl-1,1-diphosphonate
tetraisopropyl 2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethyl-1,1-biphosphonate
SCHEMBL1648488
DB12276
DTXSID80925540
tetrapropan-2-yl [2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethane-1,1-diyl]bis(phosphonate)
apomine/tetraisopropyl-(3,5-di-tert-butyl-4-hydroxyphenyl)ethyl-1,1-diphosphonate
skf 99085; sr 45023a; sr 9223i
Q27281635
tetraisopropyl (2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethane-1,1-diyl)bis(phosphonate)
bdbm50541163
CHEMBL4639024 ,
AKOS040747834

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
"Seven solid cancer patients who participated in an ongoing Phase I study of Apomine and received the starting dose level of 125 mg/m(2)/day x 14 days every 3 weeks underwent a pharmacokinetic study on day 14 of the first course."( Phase I pharmacokinetic trial and correlative in vitro phase II tumor kinetic study of Apomine (SR-45023A), a novel oral biphosphonate anticancer drug.
Alberts, DS; Bentzen, CL; Floret, S; Garcia, DJ; Gleason-Guzman, M; Hallum, AV; Niesor, EJ; Salmon, SE; Santabarbara, P; Stratton-Custis, M, 2001
)
0.31
"These in vitro assay results, taken together with our preliminary plasma pharmacokinetic data, suggest that Apomine should be clinically active at the 125 mg/m(2) dose level."( Phase I pharmacokinetic trial and correlative in vitro phase II tumor kinetic study of Apomine (SR-45023A), a novel oral biphosphonate anticancer drug.
Alberts, DS; Bentzen, CL; Floret, S; Garcia, DJ; Gleason-Guzman, M; Hallum, AV; Niesor, EJ; Salmon, SE; Santabarbara, P; Stratton-Custis, M, 2001
)
0.31
" These were the identification of an appropriate base model, calculation of the empirical Bayes estimates of the primary pharmacokinetic parameters, covariate screening, forward stepwise addition of covariates using the likelihood ratio test as a model selection criteria, and backwards elimination to obtain the final model."( Population pharmacokinetics of APOMINE: a meta-analysis in cancer patients and healthy males.
Bentzen, C; Bonate, PL; Floret, S, 2004
)
0.32
" The half-life of apomine after three weeks of once-daily dosing was 41 h in cancer patients and 32 h in healthy males."( Population pharmacokinetics of APOMINE: a meta-analysis in cancer patients and healthy males.
Bentzen, C; Bonate, PL; Floret, S, 2004
)
0.32

Bioavailability

ExcerptReferenceRelevance
" Food also decreased relative bioavailability by 36%."( Population pharmacokinetics of APOMINE: a meta-analysis in cancer patients and healthy males.
Bentzen, C; Bonate, PL; Floret, S, 2004
)
0.32

Dosage Studied

ExcerptRelevanceReference
" The half-life of apomine after three weeks of once-daily dosing was 41 h in cancer patients and 32 h in healthy males."( Population pharmacokinetics of APOMINE: a meta-analysis in cancer patients and healthy males.
Bentzen, C; Bonate, PL; Floret, S, 2004
)
0.32
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)EC50 (µMol)0.67300.47000.76901.1000AID1656767; AID1720618
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (10)

Processvia Protein(s)Taxonomy
cholesterol biosynthetic process3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
visual learning3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
coenzyme A metabolic process3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
negative regulation of protein catabolic process3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
negative regulation of protein secretion3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
long-term synaptic potentiation3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
regulation of ERK1 and ERK2 cascade3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
negative regulation of amyloid-beta clearance3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
isoprenoid biosynthetic process3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
sterol biosynthetic process3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (5)

Processvia Protein(s)Taxonomy
hydroxymethylglutaryl-CoA reductase (NADPH) activity3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
protein binding3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
GTPase regulator activity3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
NADPH binding3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
coenzyme A binding3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (3)

Processvia Protein(s)Taxonomy
peroxisomal membrane3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
endoplasmic reticulum3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
endoplasmic reticulum membrane3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
endoplasmic reticulum membrane3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
peroxisomal membrane3-hydroxy-3-methylglutaryl-coenzyme A reductaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (6)

Assay IDTitleYearJournalArticle
AID1720618Induction of degradation of Flag-tagged human HMGCR-dCat-ELuc membrane domain (1 to 499 residues) expressed in HEK293 cells assessed as reduction in HMGCR-dCat-Eluc protein level after 4 hrs by luciferase reporter assay2020Bioorganic & medicinal chemistry, 07-15, Volume: 28, Issue:14
Bisphosphonate esters interact with HMG-CoA reductase membrane domain to induce its degradation.
AID1656767Induction of human HMGCR-dCat-ELuc degradation expressed in HEK293 cells assessed as reduction in luciferase activity after 4 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.
AID1656773Induction of human HMGCR-dCat-ELuc degradation expressed in HEK293 cells assessed as reduction in luciferase activity at 10 uM measured at <4 hrs in presence of VCP inhibitor CB5083 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.
AID1656771Inhibition of SREBP (unknown origin) expressed in HEK293 cells assessed as reduction in LDLr promotor activity after 24 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.
AID1720621Cytotoxicity against human HEK293 cells assessed as cell viability at 0.01 to 10 uM incubated for 4 hrs by CytoRed viability assay2020Bioorganic & medicinal chemistry, 07-15, Volume: 28, Issue:14
Bisphosphonate esters interact with HMG-CoA reductase membrane domain to induce its degradation.
AID1656772Induction of human HMGCR-dCat-ELuc degradation expressed in HEK293 cells assessed as reduction in luciferase activity at 10 uM measured at <4 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.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (15)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's12 (80.00)29.6817
2010's1 (6.67)24.3611
2020's2 (13.33)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 12.02

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 weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index12.02 (24.57)
Research Supply Index2.89 (2.92)
Research Growth Index4.91 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (12.02)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials2 (13.33%)5.53%
Reviews1 (6.67%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other12 (80.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]