Details of the Drug

General Information of Drug (ID: DM4R657)

• Drug Name: toxaphene
• Synonyms: octachlorocamphene

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); 411.8
  Logarithm of the Partition Coefficient (xlogp); 4.7
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 0
• Chemical Identifiers:
  Formula: C10H8Cl8
  IUPAC Name: 1,4,5,6,7,7-hexachloro-2,2-bis(chloromethyl)-3-methylidenebicyclo[2.2.1]heptane
  Canonical SMILES: C=C1C(C2(C(C(C1(C2(Cl)Cl)Cl)Cl)Cl)Cl)(CCl)CCl
  InChI: InChI=1S/C10H8Cl8/c1-4-7(2-11,3-12)9(16)6(14)5(13)8(4,15)10(9,17)18/h5-6H,1-3H2
  InChIKey: OEJNXTAZZBRGDN-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5284469
  CAS Number: 8001-35-2
  TTD ID: D0X6OV

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Estrogen-related receptor-alpha (ESRRA)	TTPNQAC	ERR1_HUMAN	Antagonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Gene/Protein Processing	[3]
Beta-ureidopropionase	OTAIY2T8	BUP1_HUMAN	Drug Response	[4]
Breast cancer type 1 susceptibility protein (BRCA1)	OT5BN6VH	BRCA1_HUMAN	Gene/Protein Processing	[5]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[5]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Gene/Protein Processing	[6]
Formin-2 (FMN2)	OTUY7BSV	FMN2_HUMAN	Drug Response	[4]
Gap junction alpha-1 protein (GJA1)	OTT94MKL	CXA1_HUMAN	Gene/Protein Processing	[7]
Gelsolin (GSN)	OT4KS2UU	GELS_HUMAN	Protein Interaction/Cellular Processes	[8]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[9]
Paxillin (PXN)	OTVMMUOF	PAXI_HUMAN	Protein Interaction/Cellular Processes	[8]

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-related receptor-alpha (ESRRA)	DTT	ESRRA	9.34E-01	1.47E-02	0.06
Estrogen-related receptor-alpha (ESRRA)	DTT	ESRRA	2.09E-01	-0.07	-0.62

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: 2830).
• [2] Two organochlorine pesticides, toxaphene and chlordane, are antagonists for estrogen-related receptor alpha-1 orphan receptor. Cancer Res. 1999 Sep 15;59(18):4519-24.
• [3] Modulation of aromatase activity and mRNA by various selected pesticides in the human choriocarcinoma JEG-3 cell line. Toxicology. 2006 Nov 10;228(1):98-108.
• [4] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.
• [5] Inhibition of E2-induced expression of BRCA1 by persistent organochlorines. Breast Cancer Res. 2002;4(6):R12. doi: 10.1186/bcr461. Epub 2002 Jul 24.
• [6] Differential effects of a complex organochlorine mixture on the proliferation of breast cancer cell lines. Environ Res. 2011 Apr;111(3):337-47. doi: 10.1016/j.envres.2011.01.010. Epub 2011 Feb 5.
• [7] Inhibition of gap junctional intercellular communication in normal human breast epithelial cells after treatment with pesticides, PCBs, and PBBs, alone or in mixtures. Environ Health Perspect. 1996 Feb;104(2):192-200. doi: 10.1289/ehp.96104192.
• [8] Toxaphene, but not beryllium, induces human neutrophil chemotaxis and apoptosis via reactive oxygen species (ROS): involvement of caspases and ROS in the degradation of cytoskeletal proteins. Clin Immunol. 2002 Jul;104(1):40-8. doi: 10.1006/clim.2002.5226.
• [9] Identification of new human pregnane X receptor ligands among pesticides using a stable reporter cell system. Toxicol Sci. 2006 Jun;91(2):501-9.