Page last updated: 2024-12-06

squaric acid dibutyl ester

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

Description

Squaric acid dibutyl ester is a cyclic diketone known for its high reactivity and potential applications in various fields. It is often synthesized through the reaction of squaric acid with butanol in the presence of an acid catalyst. The compound exhibits interesting pharmacological effects, particularly as a potent inhibitor of cytochrome P450 enzymes, which are involved in drug metabolism. This property makes it a potential lead compound for the development of drugs targeting specific metabolic pathways. Moreover, squaric acid dibutyl ester has shown promising results in the treatment of various diseases like cancer and inflammatory disorders. Due to its unique structural features and potential applications, squaric acid dibutyl ester is actively studied in fields such as medicinal chemistry, organic synthesis, and materials science.'

squaric acid dibutyl ester : A cyclic ketone and diether that is a dibutyl ether derivative of squaric acid. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID65108
CHEMBL ID2435707
CHEBI ID53612
SCHEMBL ID56180
MeSH IDM0074527

Synonyms (45)

Synonym
3,4-di-n-butoxy-3-cyclobutene-1,2-dione
dibutyl squarate ,
EU-0099926
nsc113489
nsc-113489
2892-62-8
3,4-dibutoxy-3-cyclobutene-1,2-dione, 98%
nsc 113489
squaric acid dibutyl ester
3,4-dibutoxy-3-cyclobutene-1,2-dione
AKOS002138099
1,2-dibutyl squarate
squaric acid dibutylester
sadbe
CHEBI:53612 ,
3,4-dibutoxycyclobut-3-ene-1,2-dione
D2203
A819679
unii-4rto57vg65
4rto57vg65 ,
FT-0614214
AM20090383
3-cyclobutene-1,2-dione, 3,4-dibutoxy-
EPITOPE ID:115137
squaric acid dibutylester [who-dd]
squaric acid dibutylester [mi]
sqx-770
sqx770
CHEMBL2435707
SCHEMBL56180
1,2-dibutoxy-1-cyclobutene-3,4-dione
1,2-dibutoxy-1-cyclobutene -3,4-dione
AC-22927
DTXSID30183113
mfcd00037150
J-017327
CS-0041921
DB12223
DS-3421
SY048874
Q26841197
squaric-acid-dibutyl-ester
3,4-dibutoxy-cyclobut-3-ene-1,2-dione
F90387
dibutyl squarate, reference standard

Research Excerpts

Overview

Squalic acid dibutyl ester (SADBE) is a commonly used treatment for verruca vulgaris of childhood.

ExcerptReferenceRelevance
"Squaric acid dibutyl ester (SADBE) is a commonly used treatment for verruca vulgaris of childhood. "( Adjunctive trichloroacetic acid therapy enhances squaric acid response to verruca vulgaris.
Silverberg, JI; Silverberg, NB, 2012
)
1.82
"Squaric acid dibutyl ester (SADBE) is a known contact sensitizer, but dose-response data are not defined."( Determination of in vivo dose response and allergen-specific T cells in subjects contact-sensitized to squaric acid dibutyl ester.
Baron, ED; Camouse, MM; Cooper, KD; Gerberick, F; Hulette, B; Nedorost, ST; Ryan, CA; Stevens, SR; Swick, AR; Tinkle, SS,
)
1.79

Toxicity

ExcerptReferenceRelevance
" This eruption represents a rare side effect which could be controlled with corticosteroids given both systemically and topically."( Erythema multiforme-like eruptions: a rare side effect of topical immunotherapy with diphenylcyclopropenone.
Happle, R; Perret, CM; Steijlen, PM; Zaun, H, 1990
)
0.28
" Four patients discontinued the use of SADBE because of adverse effects."( Examining the efficacy and safety of squaric acid therapy for treatment of recalcitrant warts in children.
Morrell, DS; Pandey, S; Wilmer, EN,
)
0.13

Dosage Studied

Squaric acid dibutyl ester (SADBE) is a known contact sensitizer, but dose-response data are not defined.

ExcerptRelevanceReference
" Both the sensitization and challenge phases provided similar dose-response curves, demonstrating a threshold followed by a shallow linear increase and eventual plateau at increasing doses."( Insights into the quantitative relationship between sensitization and challenge for allergic contact dermatitis reactions.
Kashon, ML; Luster, MI; Scott, AE; Tinkle, SS; Yucesoy, B, 2002
)
0.31
"Squaric acid dibutyl ester (SADBE) is a known contact sensitizer, but dose-response data are not defined."( Determination of in vivo dose response and allergen-specific T cells in subjects contact-sensitized to squaric acid dibutyl ester.
Baron, ED; Camouse, MM; Cooper, KD; Gerberick, F; Hulette, B; Nedorost, ST; Ryan, CA; Stevens, SR; Swick, AR; Tinkle, SS,
)
1.79
"This study establishes the in vivo dose-response characteristics of immune reactivity to SADBE and antigen-specific T-cell reactivity."( Determination of in vivo dose response and allergen-specific T cells in subjects contact-sensitized to squaric acid dibutyl ester.
Baron, ED; Camouse, MM; Cooper, KD; Gerberick, F; Hulette, B; Nedorost, ST; Ryan, CA; Stevens, SR; Swick, AR; Tinkle, SS,
)
0.35
"Differences in immune characteristics, including immune gene expression by peripheral blood mononuclear cells (PBMCs), correlating with herpes labialis and good or poor immune control of herpes simplex virus type 1 (HSV-1), and how these characteristics change after dosing with squaric acid dibutyl ester (SADBE), were investigated."( Immune characteristics correlating with HSV-1 immune control and effect of squaric acid dibutyl ester on immune characteristics of subjects with frequent herpes labialis episodes.
Kren, BT; Matson, MA; McTavish, H; Shekels, LL; Zeller, JC; Zerebiec, KW, 2019
)
0.92
" On day 1 after blood collection the subjects with frequent outbreaks were dosed topically on the arm once with SADBE, and their PBMCs were collected and tested 8 weeks later."( Immune characteristics correlating with HSV-1 immune control and effect of squaric acid dibutyl ester on immune characteristics of subjects with frequent herpes labialis episodes.
Kren, BT; Matson, MA; McTavish, H; Shekels, LL; Zeller, JC; Zerebiec, KW, 2019
)
0.74
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
immunological adjuvantA substance that augments, stimulates, activates, potentiates, or modulates the immune response at either the cellular or humoral level. A classical agent (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contains bacterial antigens. It could also be endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Its mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy is related to its antigen-specific immunoadjuvanticity.
allergenA chemical compound, or part thereof, which causes the onset of an allergic reaction by interacting with any of the molecular pathways involved in an allergy.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
cyclic ketone
dietherA polyether in which the number of ether linkages is 2.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (6)

Assay IDTitleYearJournalArticle
AID775980Selectivity index, ratio of IC50 for HEK293T cells to IC50 for ring stage of Plasmodium falciparum W2 infected in human RBC2013European journal of medicinal chemistry, Nov, Volume: 69Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents.
AID775981Cytotoxicity against mouse NIH/3T3 cells assessed as cell viability after 48 hrs by MTT assay2013European journal of medicinal chemistry, Nov, Volume: 69Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents.
AID775982Antiplasmodial activity against ring stage of chloroquine-resistant Plasmodium falciparum W2 infected in human RBC after 48 hrs by flow cytometric analysis2013European journal of medicinal chemistry, Nov, Volume: 69Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents.
AID775984Inhibition of papaya papain using Z-Leu-Leu-Arg-AMC as substrate after 30 mins by fluorescence microplate reader analysis2013European journal of medicinal chemistry, Nov, Volume: 69Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents.
AID775983Inhibition of Plasmodium falciparum falcipain-2 using Z-Leu-Arg-AMC as substrate preincubated for 10 mins followed by substrate addition by spectrofluorometric analysis2013European journal of medicinal chemistry, Nov, Volume: 69Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents.
AID775979Cytotoxicity against HEK293T cells assessed as cell viability after 48 hrs by MTT assay2013European journal of medicinal chemistry, Nov, Volume: 69Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (113)

TimeframeStudies, This Drug (%)All Drugs %
pre-199032 (28.32)18.7374
1990's27 (23.89)18.2507
2000's26 (23.01)29.6817
2010's21 (18.58)24.3611
2020's7 (6.19)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 35.06

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

MetricThis Compound (vs All)
Research Demand Index35.06 (24.57)
Research Supply Index4.94 (2.92)
Research Growth Index4.53 (4.65)
Search Engine Demand Index48.61 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (35.06)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials14 (11.20%)5.53%
Reviews14 (11.20%)6.00%
Case Studies26 (20.80%)4.05%
Observational1 (0.80%)0.25%
Other70 (56.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (6)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Clinical Trial to Test the Safety and Efficacy of Squaric Acid Dibutyl Ester for the Treatment of Herpes Labialis [NCT01971385]Phase 154 participants (Actual)Interventional2013-10-31Completed
A Phase 2, Multi-site, Randomized, Double-blind, Vehicle-controlled Study of the Efficacy and Safety of Squaric Acid Dibutyl Ester (SADBE) in Subjects With Recurrent Herpes Labialis - Single Versus Two-dose Arm Application [NCT02965781]Phase 1/Phase 2139 participants (Actual)Interventional2016-12-31Completed
A Phase I Study of the Immune Response to Herpes Simplex Virus Type 1 (HSV-1) and General Immune Health in Subjects Infected With HSV-1 [NCT03661541]Phase 136 participants (Actual)Interventional2017-03-02Completed
A Phase 2, Muti-Center Study of Repeat Dosing of Squaric Acid Dibutyl Ester in Subjects With Herpes Labialis [NCT03521479]Phase 240 participants (Actual)Interventional2018-03-12Terminated(stopped due to Study drug out of specification)
Neoadjuvant Squaric Acid Dibutylester Treatment of Melanocytes in Congenital Melanocytic Nevi [NCT04999631]Early Phase 130 participants (Anticipated)Interventional2022-01-01Not yet recruiting
Biologics and Blistering - Using a Contact Dermatitis Model With Biologic Medications to Study Skin Inflammation Through Suction Blistering [NCT05535738]Phase 2/Phase 345 participants (Anticipated)Interventional2022-11-15Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT01971385 (1) [back to overview]Subjects With at Least One Form of Contact With Study Staff With no Herpes Labialis Outbreaks Within 119 Days of Sensitization
NCT02965781 (2) [back to overview]Days to Next Herpes Labialis (Cold Sore) Episode From 43 Days After the First Dose up to 121 Days After the First Dose
NCT02965781 (2) [back to overview]Number of Outbreaks Beginning 43 Days After the First Dose up to 12 Months
NCT03521479 (1) [back to overview]Local and Generalized Adverse Events
NCT03661541 (3) [back to overview]Immune Monitoring - PBMC Proliferation
NCT03661541 (3) [back to overview]Immune Monitoring - PBMC Proliferation
NCT03661541 (3) [back to overview]Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline

Subjects With at Least One Form of Contact With Study Staff With no Herpes Labialis Outbreaks Within 119 Days of Sensitization

Percent of subjects with no reported herpes labialis outbreak within 119 days of sensitization over total number of subjects after one form of contact with study staff (NCT01971385)
Timeframe: 8 months

Interventionpercentage of particpants (Number)
2% Squaric Acid Sensitization62.96
Placebo Solution20

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Number of Outbreaks Beginning 43 Days After the First Dose up to 12 Months

The number of new herpes labialis episodes per subject during the 12-month follow up period following the first drug dose, beginning day 43 after the first dose (NCT02965781)
Timeframe: From day 43 after the first dose up to 12 months

Interventionoutbreaks per participant (Mean)
Placebo Application (DMSO Only-No SADBE)0.610
Two SADBE Applications0.500
One SADBE Application0.231

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Local and Generalized Adverse Events

Local and generalized adverse events with repeat topical application of 2% and 0.5% squaric acid dibutyl ester (SADBE) in subjects with frequent herpes labialis (4 or more episodes in the previous 12 months). (NCT03521479)
Timeframe: 9 months

,,,
Interventionevents (Number)
Localized reaction (rash, erythema, itching/pruritus, warmth/burning) at application siteGeneralized adverse events (related, possible or greater)Generalized adverse event (unrelated)
Group A2424
Group B1437
Group C1716
Group D604

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Immune Monitoring - PBMC Proliferation

PBMC proliferation in response to 3 stimuli: HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract. (NCT03661541)
Timeframe: Baseline

,,
Interventionpercent proliferation (Mean)
HSV-1-infected cell extractsHSV-1 virusCandida extractNormalized all three stimuli
1 to 2 Herpes Labialis Outbreaks19.2611.714.8583.21
6 or More Herpes Labialis Outbreaks16.738.264.4768.33
Zero Herpes Labialis Outbreaks20.1912.707.8399.98

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Immune Monitoring - PBMC Proliferation

PBMC proliferation in response to 3 stimuli: HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract. (NCT03661541)
Timeframe: Day 1 and 8 weeks from Day 1 (Initial visit) +/- 7 days for subjects with 6 or more herpes labalis outbreaks

,
Interventionpercent proliferation (Mean)
HSV-1-infected cell extractsHSV-1 virusCandida extractNormalized all three stimuli
6 or More Herpes Labialis Outbreaks at 8 Weeks16.9613.377.3599.97
6 or More Herpes Labialis Outbreaks at Day 116.738.264.4773.75

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Ratio of Absolute Gene Expression of IFNG and IL5 in PBMCs Between 8 Weeks and Baseline

RNA gene expression of interleukin-5 (IL5) and interferon gamma (IFNG) genes in PBMCs exposed in vitro to 4 conditions: no stimulus, HSV-1 virus, HSV-1-infected cell extracts, and Candida albicans extract. Measure is qRT-PCR crossing threshold (Ct), where a lower number is higher gene expression. A lower Ct of 1 is approximately a 2-fold higher expression level of the gene. (NCT03661541)
Timeframe: Baseline and 8 weeks after baseline (Day 1) +/- 7 days for subjects with less than 6 herpres labialis outbreaks in 12 months, relative to baseline for subjects with 6 or greater herpes labialis outbreaks

,,,
Interventionq-RT-PCR crossing threshold cycle (Ct) (Mean)
IL5 in negative controlIL5 with HSV-1-infected cell extract stimulusIL5 with HSV-1 virus stimulusIL5 with Candida stimulusIFNG in negative controlIFNG in HSV-1-infected cell extracts stimulusIFNG in HSV-1 stimulusIFNG in Candida stimulus
Group A, Day 57. Subjects With 6 or More Outbreaks, 8 Weeks After Single Dose of SADBE.11.43110.62710.59510.5369.7183.5223.9235.327
Group A: 6 or More Herpes Labialis Outbreaks, Day 110.0739.6249.74710.68010.0336.0407.3848.421
Group B: 1 or 2 Herpes Labialis Outbreaks in Prior 12 Months, Day 111.38010.98310.73610.80610.2103.8985.5546.167
Group C: Zero Herpes Labialis Outbreaks in Prior 12 Months, Day 110.71110.98610.41411.0519.7294.9925.7897.336

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