T3DB: Isoxaflutole

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (8)XML

Targets (8)

Record Information

Version

2.0

Creation Date

2013-04-25 07:56:52 UTC

Update Date

2014-12-24 20:26:33 UTC

Accession Number

T3D3868

Identification

Common Name

Isoxaflutole

Class

Small Molecule

Description

Isoxaflutole is an isoxazole herbicide that is approved for use on field corn. It demonstrates developmental toxicity and has been classified as a Group B2 carcinogen (probable human carcinogen).

Compound Type

Ester
Ether
Herbicide
Organic Compound
Organofluoride
Pesticide
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(5-Cyclopropyl-1,2-oxazol-4-yl)[2-(methylsulfonyl)-4-(trifluoromethyl)phenyl]methanone
(5-Cyclopropyl-4-isoxazolyl)(2-(methylsulfonyl)-4-(trifluoromethyl)phenyl)methanone
(5-Cyclopropyl-4-isoxazolyl)[2-(methylsulfonyl)-4-(trifluoromethyl)phenyl]methanone
4-(2-Methanesulphonyl-4-trifluoromethylbenzoyl)-5-cyclopropyl Isoxazole
5-Cyclopropyl-4-[2-(methylsulfonyl)-4-(trifluoromethyl)benzoyl]isoxazole
Annex
Merlin

Chemical Formula

C₁₅H₁₂F₃NO₄S

Average Molecular Mass

359.320 g/mol

Monoisotopic Mass

359.044 g/mol

CAS Registry Number

141112-29-0

IUPAC Name

5-cyclopropyl-4-[2-methanesulfonyl-4-(trifluoromethyl)benzoyl]-1,2-oxazole

Traditional Name

isoxaflutole

SMILES

CS(=O)(=O)C1=C(C=CC(=C1)C(F)(F)F)C(=O)C1=C(ON=C1)C1CC1

InChI Identifier

InChI=1S/C15H12F3NO4S/c1-24(21,22)12-6-9(15(16,17)18)4-5-10(12)13(20)11-7-19-23-14(11)8-2-3-8/h4-8H,2-3H2,1H3

InChI Key

InChIKey=OYIKARCXOQLFHF-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.

Kingdom

Organic compounds

Super Class

Organic oxygen compounds

Class

Organooxygen compounds

Sub Class

Carbonyl compounds

Direct Parent

Aryl-phenylketones

Alternative Parents

Substituents

Aryl-phenylketone
Trifluoromethylbenzene
Benzenesulfonyl group
Benzoyl
5-cyclopropylisoxazole
Cyclopropylisoxazole
Monocyclic benzene moiety
Benzenoid
Azole
Heteroaromatic compound
Isoxazole
Sulfonyl
Sulfone
Oxacycle
Azacycle
Organoheterocyclic compound
Organic oxide
Organosulfur compound
Organonitrogen compound
Organofluoride
Organohalogen compound
Alkyl halide
Organic nitrogen compound
Alkyl fluoride
Hydrocarbon derivative
Organopnictogen compound
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.047 g/L	ALOGPS
logP	2.75	ALOGPS
logP	2.14	ChemAxon
logS	-3.9	ALOGPS
pKa (Strongest Acidic)	19.6	ChemAxon
pKa (Strongest Basic)	-0.48	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	77.24 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	80.4 m³·mol⁻¹	ChemAxon
Polarizability	30.32 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-Q (Non-derivatized)	splash10-0h00-4890000000-16de1b16d662eeb3671d	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0fyo-9488000000-887fd01cfd26aca275c1	2021-09-23	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-056r-9006000000-3160f253be09f3b06015	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-004i-9000000000-77f6b9470673a62f9b03	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-004i-9000000000-b0b350c966384dd253ad	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-01t9-9000000000-838bde6d65ef6fda1c34	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-03di-9000000000-085d5f6b7b66d4f7baa8	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-03di-9000000000-b652074dbf5786951aa4	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-03di-9000000000-48756ff8f6599474e2af	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-03di-9000000000-239fd89f2b17e9b96259	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , negative	splash10-03di-9000000000-6cf7fa6c8add9de48dbc	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0udi-0091000000-2b4eb379d0ae70ec0514	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0udi-0090000000-512447190c1396368865	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0udi-0090000000-5ea6d1d4d0f82315c191	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0udi-0790000000-79103ab1eea6c3f63cd2	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-03xr-0920000000-5c10e46549621e7ebdd4	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-03di-1900000000-d3367387df56d90d6f4f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0fc3-4900000000-9ea0aba2553e5854c385	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-004l-9500000000-267509275d294e394380	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-004i-9200000000-18a96a885de7ef83345a	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-03xr-0920000000-4f70e22631322546a172	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-03di-0009000000-1ba5dcc6f3d9e6c618eb	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03el-2469000000-188fb4c8ba3cb91bcf05	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00kr-8391000000-38889804386798b2f10e	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4i-1009000000-3212fd9941fee4e06cb1	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0a6r-5049000000-e8427dd8abd5c22b30e5	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-004i-9110000000-374a8687c2038b666dd3	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Not Available

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

Not listed by IARC.

Uses/Sources

This is a man-made compound that is used as a pesticide.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

84098

ChEMBL ID

CHEMBL1887147

ChemSpider ID

75869

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

T3D3868.pdf

General References

Not Available

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1

General Function:: Transferase activity
Specific Function:: Synthesizes the second messagers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system.
Gene Name:: CD38
Uniprot ID:: P28907
Molecular Weight:: 34328.145 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	1.48 uM	BSK_SAg_CD38_up	BioSeek

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

2. Epidermal growth factor receptor

General Function:: Ubiquitin protein ligase binding
Specific Function:: Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.Isoform 2 may act as an antagonist of EGF action.
Gene Name:: EGFR
Uniprot ID:: P00533
Molecular Weight:: 134276.185 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	1.48 uM	BSK_hDFCGF_EGFR_up	BioSeek

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

3. Interleukin-1 alpha

General Function:: Cytokine activity
Specific Function:: Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.
Gene Name:: IL1A
Uniprot ID:: P01583
Molecular Weight:: 30606.29 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	1.48 uM	BSK_BE3C_IL1a_up	BioSeek

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

4. Interstitial collagenase

General Function:: Zinc ion binding
Specific Function:: Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.
Gene Name:: MMP1
Uniprot ID:: P03956
Molecular Weight:: 54006.61 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	1.48 uM	BSK_hDFCGF_MMP1_up	BioSeek

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

5. C-X-C motif chemokine 10

General Function:: Receptor binding
Specific Function:: Chemotactic for monocytes and T-lymphocytes. Binds to CXCR3.
Gene Name:: CXCL10
Uniprot ID:: P02778
Molecular Weight:: 10880.915 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	4.44 uM	BSK_BE3C_IP10_up	BioSeek

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

6. Vascular cell adhesion protein 1

General Function:: Primary amine oxidase activity
Specific Function:: Important in cell-cell recognition. Appears to function in leukocyte-endothelial cell adhesion. Interacts with integrin alpha-4/beta-1 (ITGA4/ITGB1) on leukocytes, and mediates both adhesion and signal transduction. The VCAM1/ITGA4/ITGB1 interaction may play a pathophysiologic role both in immune responses and in leukocyte emigration to sites of inflammation.
Gene Name:: VCAM1
Uniprot ID:: P19320
Molecular Weight:: 81275.43 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	4.44 uM	BSK_4H_VCAM1_up	BioSeek

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

7. Cytochrome P450 2B6

General Function:: Steroid hydroxylase activity
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:: CYP2B6
Uniprot ID:: P20813
Molecular Weight:: 56277.81 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	4.79 uM	CLZD_CYP2B6_24	CellzDirect

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

8. Cytochrome P450 3A4

General Function:: Vitamin d3 25-hydroxylase activity
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:: CYP3A4
Uniprot ID:: P08684
Molecular Weight:: 57342.67 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	6.99 uM	CLZD_CYP3A4_24	CellzDirect

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Isoxaflutole (T3D3868)

Structure for T3D3868: Isoxaflutole

Targets

Binding/Activity Constants

References

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