Compounds > sb-706375
Page last updated: 2024-11-13

sb-706375

Description

SB-706375: nonpeptidic urotensin-II receptor antagonist; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID21023902
CHEMBL ID522770
SCHEMBL ID5835165
MeSH IDM0491071

Synonyms (22)

Synonym
gtpl2165
2-bromo-4,5-dimethoxy-n-[3-[(3r)-1-methylpyrrolidin-3-yl]oxy-4-(trifluoromethyl)phenyl]benzenesulfonamide
sb706375
(r)-2-bromo-4,5-dimethoxy-n-(3-(1-methylpyrrolidin-3-yloxy)-4-(trifluoromethyl)phenyl)benzenesulfonamide
bdbm50249878
sb-706375
CHEMBL522770 ,
SCHEMBL5835165
2-bromo-4,5-dimethoxy-n-[3-[[(3r)-1-methyl-3-pyrrolidinyl]oxy]-4-(trifluoromethyl)phenyl]benzenesulfonamide
733734-61-7
sb 706375
AKOS024458280
NCGC00379177-01
2-bromo-4,5-dimethoxyn-(3-(((3r)-1-methyl-3-pyrrolidinyl)oxy)-4-(trifluoromethyl)phenyl)benzenesulfonamide
96711H97SD ,
bpowqjyamdeaff-cybmujfwsa-n
(r)-2-bromo-4,5-dimethoxy-n-(3-((1-methylpyrrolidin-3-yl)oxy)-4-(trifluoromethyl)phenyl)benzenesulfonamide
benzenesulfonamide,2-bromo-4,5-dimethoxy-n-[3-[[(3r)-1-methyl-3-pyrrolidinyl]oxy]-4-(trifluoromethyl)phenyl]-
Q27088738
benzenesulfonamide, 2-bromo-4,5-dimethoxy-n-[3-[[(3r)-1-methyl-3-pyrrolidinyl]oxy]-4-(trifluoromethyl)phenyl]-
unii-96711h97sd
cid 21023902

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
"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 (9)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency2.13170.01237.983543.2770AID1645841
GVesicular stomatitis virusPotency23.91850.01238.964839.8107AID1645842
cytochrome P450 2D6Homo sapiens (human)Potency23.91850.00108.379861.1304AID1645840
Interferon betaHomo sapiens (human)Potency23.91850.00339.158239.8107AID1645842
HLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)Potency23.91850.01238.964839.8107AID1645842
Inositol hexakisphosphate kinase 1Homo sapiens (human)Potency23.91850.01238.964839.8107AID1645842
cytochrome P450 2C9, partialHomo sapiens (human)Potency23.91850.01238.964839.8107AID1645842
[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)
Urotensin-2 receptorRattus norvegicus (Norway rat)IC50 (µMol)0.03400.03403.16687.6000AID445487
Urotensin-2 receptorHomo sapiens (human)IC50 (µMol)0.00930.00500.05720.3200AID445489; AID741608; AID741609
Urotensin-2 receptorHomo sapiens (human)Ki0.00670.00080.67724.0000AID349869; AID445488
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (50)

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)
signal transductionUrotensin-2 receptorHomo sapiens (human)
blood circulationUrotensin-2 receptorHomo sapiens (human)
regulation of blood pressureUrotensin-2 receptorHomo sapiens (human)
blood vessel diameter maintenanceUrotensin-2 receptorHomo sapiens (human)
neuropeptide signaling pathwayUrotensin-2 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (20)

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)
G protein-coupled receptor activityUrotensin-2 receptorHomo sapiens (human)
urotensin II receptor activityUrotensin-2 receptorHomo 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)
plasma membraneUrotensin-2 receptorHomo sapiens (human)
membraneUrotensin-2 receptorHomo sapiens (human)
plasma membraneUrotensin-2 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (18)

Assay IDTitleYearJournalArticle
AID741609Displacement of [125I]-U2 from human recombinant urotensin2 receptor expressed in human Chem-2 cells after 4 hrs by scintillation proximity assay2013Bioorganic & medicinal chemistry letters, Apr-01, Volume: 23, Issue:7
Deconstruction of sulfonamide inhibitors of the urotensin receptor (UT) and design and synthesis of benzylamine and benzylsulfone antagonists.
AID741608Antagonist activity at recombinant human urotensin2 receptor expressed in CHO cells assessed as inhibition of urotensin2-stimulated Ca2+ mobilization after 1 hr by FLIPR assay2013Bioorganic & medicinal chemistry letters, Apr-01, Volume: 23, Issue:7
Deconstruction of sulfonamide inhibitors of the urotensin receptor (UT) and design and synthesis of benzylamine and benzylsulfone antagonists.
AID349869Binding affinity to urotensin-2 receptor2009Journal of medicinal chemistry, May-14, Volume: 52, Issue:9
Sequence-derived three-dimensional pharmacophore models for G-protein-coupled receptors and their application in virtual screening.
AID445491Oral bioavailability in rat2009Journal of medicinal chemistry, Dec-10, Volume: 52, Issue:23
Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits.
AID445493Vasorelaxant activity in Wistar rat thoracic aortic ring assessed as inhibition of KCl-induced contraction at 100 nM2009Journal of medicinal chemistry, Dec-10, Volume: 52, Issue:23
Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits.
AID445489Antagonist activity at urotensin 2 receptor in human RMS13 cells assessed as inhibition of urotensin 2-induced intracellular calcium mobilization after 1 hr by FLIPR assay2009Journal of medicinal chemistry, Dec-10, Volume: 52, Issue:23
Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits.
AID445488Displacement of [125I]urotensin 2 from urotensin 2 receptor in human RMS13 cells by scintillation proximity assay2009Journal of medicinal chemistry, Dec-10, Volume: 52, Issue:23
Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits.
AID485962Antagonist activity at rat urotensin 2 receptor expressed in CHO cells assessed as calcium mobilization at 100 nM by FLIPR2010Journal of medicinal chemistry, Apr-08, Volume: 53, Issue:7
Urotensin-II receptor modulators as potential drugs.
AID445487Antagonist activity at rat urotensin 2 receptor expressed in CHOK1 cells assessed as inhibition of urotensin 2-induced intracellular calcium mobilization after 1 hr by FLIPR assay2009Journal of medicinal chemistry, Dec-10, Volume: 52, Issue:23
Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits.
AID445494Inhibition of ear flushing in Sprague-Dawley rat ear-flush model assessed as complete attenuation of urotensin 2-induced increase in ear pinna temperature at 10 mg/kg, iv administered 15 mins prior to urotensin 2 challenge2009Journal of medicinal chemistry, Dec-10, Volume: 52, Issue:23
Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits.
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.
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.
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.
AID1346323Mouse UT receptor (Urotensin receptor)2005British journal of pharmacology, Jul, Volume: 145, Issue:5
Nonpeptidic urotensin-II receptor antagonists I: in vitro pharmacological characterization of SB-706375.
AID1346351Rat UT receptor (Urotensin receptor)2005British journal of pharmacology, Jul, Volume: 145, Issue:5
Nonpeptidic urotensin-II receptor antagonists I: in vitro pharmacological characterization of SB-706375.
AID1346328Human UT receptor (Urotensin receptor)2005British journal of pharmacology, Jul, Volume: 145, Issue:5
Nonpeptidic urotensin-II receptor antagonists I: in vitro pharmacological characterization of SB-706375.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (11)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's4 (36.36)29.6817
2010's5 (45.45)24.3611
2020's2 (18.18)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 12.07

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 Index12.07 (24.57)
Research Supply Index2.48 (2.92)
Research Growth Index4.56 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (12.07)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews2 (18.18%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other9 (81.82%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
urea
pseudourea: clinical use; structure. isourea : A carboximidic acid that is the imidic acid tautomer of urea, H2NC(=NH)OH, and its hydrocarbyl derivatives.		3.1410isourea;
monocarboxylic acid amide;
one-carbon compound		Daphnia magna metabolite;
Escherichia coli metabolite;
fertilizer;
flour treatment agent;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
ac 7954
3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one: a GPR14/urotensin-II receptor agonist; structure in first source		3.15102-benzopyran
act 058362
1-(2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl)-3-(2-methylquinolin-4-yl)urea: a urotensin-II receptor antagonist; structure in first source		3.8530
sb-611812
SB-611812: urotensin-II antagonist		4.0620
sb 657510
SB 657510: a urotensin II antagonist		2.0810
ConditionIndicatedRelationship StrengthStudiesTrials
Muscle Contraction
A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.		02.0210
Rhabdomyosarcoma
A malignant solid tumor arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites. It is divided into four distinct types: pleomorphic, predominantly in male adults; alveolar (RHABDOMYOSARCOMA, ALVEOLAR), mainly in adolescents and young adults; embryonal (RHABDOMYOSARCOMA, EMBRYONAL), predominantly in infants and children; and botryoidal, also in young children. It is one of the most frequently occurring soft tissue sarcomas and the most common in children under 15. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p2186; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1647-9)		02.0210
Congenital Zika Syndrome
[description not available]		02.2510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		02.2510
Zika Virus Infection
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.		02.2510
Injury, Myocardial Reperfusion
[description not available]		02.2110
Necrosis
The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.		07.2110
Blood Pressure, High
[description not available]		02.0810
Hypertension
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.		02.0810
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