Details of the Drug

General Information of Drug (ID: DMEDGKO)

• Drug Name: dibutyl phthalate
• Synonyms: di-n-butyl phthalate; n-butyl phthalate; nutyl phthalate

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 278.34
  Logarithm of the Partition Coefficient (xlogp); 4.7
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 4
• Chemical Identifiers:
  Formula: C16H22O4
  IUPAC Name: dibutyl benzene-1,2-dicarboxylate
  Canonical SMILES: CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC
  InChI: InChI=1S/C16H22O4/c1-3-5-11-19-15(17)13-9-7-8-10-14(13)16(18)20-12-6-4-2/h7-10H,3-6,11-12H2,1-2H3
  InChIKey: DOIRQSBPFJWKBE-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3026
  ChEBI ID: CHEBI:34687
  CAS Number: 84-74-2
  TTD ID: D07FLG
  INTEDE ID: DR0481

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Transformation-sensitive protein p120 (TRPA1)	TTELV3W	TRPA1_HUMAN	Activator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1B1 (CYP1B1) Main DME	DE9QHP6	CP1B1_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Gene/Protein Processing	[4]
5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)	OTU1KZPV	AAPK2_HUMAN	Gene/Protein Processing	[5]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Gene/Protein Processing	[6]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Gene/Protein Processing	[7]
Alpha-fetoprotein (AFP)	OT9GG3ZI	FETA_HUMAN	Gene/Protein Processing	[8]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Gene/Protein Processing	[9]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Gene/Protein Processing	[10]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Gene/Protein Processing	[11]
ATP-binding cassette sub-family G member 1 (ABCG1)	OT5BG6MK	ABCG1_HUMAN	Gene/Protein Processing	[12]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Gene/Protein Processing	[13]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6295).
• [2] TRPA1 and TRPV1 activation is a novel adjuvant effect mechanism in contact hypersensitivity. J Neuroimmunol. 2009 Feb 15;207(1-2):66-74.
• [3] Inhibition of human cytochrome p450 1b1 further clarifies its role in the activation of dibenzo[a,l]pyrene in cells in culture. J Biochem Mol Toxicol. 2007;21(3):101-9.
• [4] Structure-dependent inhibition of human and rat 11beta-hydroxysteroid dehydrogenase 2 activities by phthalates. Chem Biol Interact. 2010 Jan 5;183(1):79-84.
• [5] Dibutyl phthalate induces epithelial-mesenchymal transition of renal tubular epithelial cells via the Ang II/AMPK2/Cx43 signaling pathway. Toxicology. 2023 Aug 1;494:153584. doi: 10.1016/j.tox.2023.153584. Epub 2023 Jun 24.
• [6] Integration of data from the in vitro long-term exposure study on human endothelial cells and the in silico analysis: A case of dibutyl phthalate-induced vascular dysfunction. Toxicol Lett. 2022 Mar 1;356:64-74. doi: 10.1016/j.toxlet.2021.12.006. Epub 2021 Dec 10.
• [7] Application of oligonucleotide microarray technology to toxic occupational exposures. J Toxicol Environ Health A. 2008;71(5):315-24.
• [8] Combined cytotoxicity of phthalate esters on HepG2 cells: A comprehensive analysis of transcriptomics and metabolomics. Food Chem Toxicol. 2023 Oct;180:114034. doi: 10.1016/j.fct.2023.114034. Epub 2023 Sep 12.
• [9] Development and pre-validation of an in vitro transactivation assay for detection of (anti)androgenic potential compounds using 22Rv1/MMTV cells. Reprod Toxicol. 2016 Apr;60:156-66. doi: 10.1016/j.reprotox.2016.02.006. Epub 2016 Feb 8.
• [10] The selected epigenetic effects of phthalates: DBP, BBP and their metabolites: MBP, MBzP on human peripheral blood mononuclear cells (In Vitro). Toxicol In Vitro. 2022 Aug;82:105369. doi: 10.1016/j.tiv.2022.105369. Epub 2022 Apr 27.
• [11] Dibutyl phthalate impairs steroidogenesis and a subset of LH-dependent genes in cultured human mural granulosa cell in vitro. Reprod Toxicol. 2017 Apr;69:13-18.
• [12] Di-n-butyl phthalate promotes lipid accumulation via the miR200c-5p-ABCA1 pathway in THP-1 macrophages. Environ Pollut. 2020 Sep;264:114723. doi: 10.1016/j.envpol.2020.114723. Epub 2020 May 3.
• [13] In Vitro Exposure of Human Luteinized Mural Granulosa Cells to Dibutyl Phthalate Affects Global Gene Expression. Toxicol Sci. 2017 Nov 1;160(1):180-188. doi: 10.1093/toxsci/kfx170.