Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJP46CB)

• DOT Name: Cytochrome P450 4B1 (CYP4B1)
• Synonyms: EC 1.14.14.1; CYPIVB1; Cytochrome P450-HP
• Gene Name: CYP4B1
• UniProt ID: CP4B1_HUMAN
• EC Number: 1.14.14.1
• Pfam ID: PF00067
• Sequence:
  MVPSFLSLSFSSLGLWASGLILVLGFLKLIHLLLRRQTLAKAMDKFPGPPTHWLFGHALE
  IQETGSLDKVVSWAHQFPYAHPLWFGQFIGFLNIYEPDYAKAVYSRGDPKAPDVYDFFLQ
  WIGRGLLVLEGPKWLQHRKLLTPGFHYDVLKPYVAVFTESTRIMLDKWEEKAREGKSFDI
  FCDVGHMALNTLMKCTFGRGDTGLGHRDSSYYLAVSDLTLLMQQRLVSFQYHNDFIYWLT
  PHGRRFLRACQVAHDHTDQVIRERKAALQDEKVRKKIQNRRHLDFLDILLGARDEDDIKL
  SDADLRAEVDTFMFEGHDTTTSGISWFLYCMALYPEHQHRCREEVREILGDQDFFQWDDL
  GKMTYLTMCIKESFRLYPPVPQVYRQLSKPVTFVDGRSLPAGSLISMHIYALHRNSAVWP
  DPEVFDSLRFSTENASKRHPFAFMPFSAGPRNCIGQQFAMSEMKVVTAMCLLRFEFSLDP
  SRLPIKMPQLVLRSKNGFHLHLKPLGPGSGK
• 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.
• Tissue Specificity: Detected in the liver and lung (at protein level).
• Reactome Pathway:
  Miscellaneous substrates (R-HSA-211958)
  Eicosanoids (R-HSA-211979)
  Synthesis of Leukotrienes (LT) and Eoxins (EX) (R-HSA-2142691)
  Fatty acids (R-HSA-211935)

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cytochrome P450 4B1 (CYP4B1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cytochrome P450 4B1 (CYP4B1).	[13]

12 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cytochrome P450 4B1 (CYP4B1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cytochrome P450 4B1 (CYP4B1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cytochrome P450 4B1 (CYP4B1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cytochrome P450 4B1 (CYP4B1).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cytochrome P450 4B1 (CYP4B1).	[6]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cytochrome P450 4B1 (CYP4B1).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cytochrome P450 4B1 (CYP4B1).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cytochrome P450 4B1 (CYP4B1).	[9]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Cytochrome P450 4B1 (CYP4B1).	[10]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Cytochrome P450 4B1 (CYP4B1).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Cytochrome P450 4B1 (CYP4B1).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the expression of Cytochrome P450 4B1 (CYP4B1).	[12]

References

• [1] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Differentiation-specific factors modulate epidermal CYP1-4 gene expression in human skin in response to retinoic acid and classic aryl hydrocarbon receptor ligands. J Pharmacol Exp Ther. 2006 Dec;319(3):1162-71.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Vitamin D3 transactivates the zinc and manganese transporter SLC30A10 via the Vitamin D receptor. J Steroid Biochem Mol Biol. 2016 Oct;163:77-87.
• [7] Triclosan treatment decreased the antitumor effect of sorafenib on hepatocellular carcinoma cells. Onco Targets Ther. 2018 May 18;11:2945-2954.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [10] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [11] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [12] Caffeine overcomes genistein-induced G2/M cell cycle arrest in breast cancer cells. Nutr Cancer. 2008;60(3):382-8.
• [13] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.