Details of the Drug

General Information of Drug (ID: DMRPZD4)

• Drug Name: HPTE
• Synonyms: Hydroxychlor; HPTE; p,p'-Hydroxy-DDT; 2971-36-0; p,p'-HO-DDT; 2,2-Bis(4-hydroxyphenyl)-1,1,1-trichloroethane; 1,1,1-Trichloro-2,2-bis(4-hydroxyphenyl)ethane; 4,4'-(2,2,2-trichloroethane-1,1-diyl)diphenol; 2,2-Bis(p-hydroxyphenyl)-1,1,1-trichloroethane; 4,4'-(2,2,2-Trichloroethylidene)diphenol; 1,1-Bis(4-hydroxyphenyl)-2,2,2-trichloroethane; 1,1-Bis(p-hydroxyphenyl)-2,2,2-trichloroethane; p,p'-(2,2,2-Trichloroethylidene)diphenol; NSC 7045; 1,1,1-Trichloro-2,2-bis(p-hydroxyphenyl)ethane; Phenol, 4,4'-(2,2,2-trichloroethylid

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); 317.6
  Logarithm of the Partition Coefficient (xlogp); 4.9
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 2
• Chemical Identifiers:
  Formula: C14H11Cl3O2
  IUPAC Name: 4-[2,2,2-trichloro-1-(4-hydroxyphenyl)ethyl]phenol
  Canonical SMILES: C1=CC(=CC=C1C(C2=CC=C(C=C2)O)C(Cl)(Cl)Cl)O
  InChI: InChI=1S/C14H11Cl3O2/c15-14(16,17)13(9-1-5-11(18)6-2-9)10-3-7-12(19)8-4-10/h1-8,13,18-19H
  InChIKey: IUGDILGOLSSKNE-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 76302
  ChEBI ID: CHEBI:34025
  CAS Number: 2971-36-0
  TTD ID: D0Z3NC

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Estrogen receptor beta (ESR2)	TTOM3J0	ESR2_HUMAN	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Gene/Protein Processing	[3]
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Gene/Protein Processing	[3]
17-beta-hydroxysteroid dehydrogenase type 3 (HSD17B3)	OT45D396	DHB3_HUMAN	Gene/Protein Processing	[4]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Gene/Protein Processing	[5]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Gene/Protein Processing	[6]
C-X-C chemokine receptor type 4 (CXCR4)	OTUFSBX2	CXCR4_HUMAN	Drug Response	[7]
CCN family member 5 (CCN5)	OTADU8JJ	CCN5_HUMAN	Gene/Protein Processing	[8]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Post-Translational Modifications	[9]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Gene/Protein Processing	[10]
Estrogen-related receptor gamma (ESRRG)	OTC3A0KU	ERR3_HUMAN	Protein Interaction/Cellular Processes	[11]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Estrogen receptor beta (ESR2)	DTT	ESR2	2.09E-01	-0.06	-0.17

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: 2827).
• [2] Signalling by CXC-chemokine receptors 1 and 2 expressed in CHO cells: a comparison of calcium mobilization, inhibition of adenylyl cyclase and stimulation of GTPgammaS binding induced by IL-8 and GROalpha. Br J Pharmacol. 1999 Feb;126(3):810-8.
• [3] Effects of methoxychlor and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane on 11beta-hydroxysteroid dehydrogenase activities in vitro. Toxicol Lett. 2013 Mar 27;218(1):18-23.
• [4] Effects of methoxychlor and 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane on 3beta-hydroxysteroid dehydrogenase and 17beta-hydroxysteroid dehydrogenase-3 activities in human and rat testes. Int J Androl. 2011 Apr;34(2):138-44.
• [5] Development of two androgen receptor assays using adenoviral transduction of MMTV-luc reporter and/or hAR for endocrine screening. Toxicol Sci. 2002 Mar;66(1):82-90. doi: 10.1093/toxsci/66.1.82.
• [6] A comparison of two human cell lines and two rat gonadal cell primary cultures as in vitro screening tools for aromatase modulation. Toxicol In Vitro. 2012 Feb;26(1):107-18.
• [7] Endocrine disrupting chemicals promote the growth of ovarian cancer cells via the ER-CXCL12-CXCR4 signaling axis. Mol Carcinog. 2013 Sep;52(9):715-25. doi: 10.1002/mc.21913. Epub 2012 Apr 30.
• [8] Endocrine-Disrupting Chemicals (EDCs): In Vitro Mechanism of Estrogenic Activation and Differential Effects on ER Target Genes. Environ Health Perspect. 2013 Apr;121(4):459-66. doi: 10.1289/ehp.1205951. Epub 2013 Feb 5.
• [9] Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells. Carcinogenesis. 2017 Mar 1;38(3):252-260.
• [10] Impact of environmental chemicals on key transcription regulators and correlation to toxicity end points within EPA's ToxCast program. Chem Res Toxicol. 2010 Mar 15;23(3):578-90. doi: 10.1021/tx900325g.
• [11] Structure-based Identification of Endocrine Disrupting Pesticides Targeting Breast Cancer Proteins. Toxicology. 2020 Jun;439:152459. doi: 10.1016/j.tox.2020.152459. Epub 2020 Apr 9.