Details of Drug Off-Target (DOT)

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

• DOT Name: C-C chemokine receptor type 7 (CCR7)
• Synonyms: C-C CKR-7; CC-CKR-7; CCR-7; BLR2; CDw197; Epstein-Barr virus-induced G-protein coupled receptor 1; EBI1; EBV-induced G-protein coupled receptor 1; MIP-3 beta receptor; CD antigen CD197
• Gene Name: CCR7
• UniProt ID: CCR7_HUMAN
• PDB ID: 6QZH
• Pfam ID: PF00001
• Sequence:
  MDLGKPMKSVLVVALLVIFQVCLCQDEVTDDYIGDNTTVDYTLFESLCSKKDVRNFKAWF
  LPIMYSIICFVGLLGNGLVVLTYIYFKRLKTMTDTYLLNLAVADILFLLTLPFWAYSAAK
  SWVFGVHFCKLIFAIYKMSFFSGMLLLLCISIDRYVAIVQAVSAHRHRARVLLISKLSCV
  GIWILATVLSIPELLYSDLQRSSSEQAMRCSLITEHVEAFITIQVAQMVIGFLVPLLAMS
  FCYLVIIRTLLQARNFERNKAIKVIIAVVVVFIVFQLPYNGVVLAQTVANFNITSSTCEL
  SKQLNIAYDVTYSLACVRCCVNPFLYAFIGVKFRNDLFKLFKDLGCLSQEQLRQWSSCRH
  IRRSSMSVEAETTTTFSP
• Function: Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions.
• Tissue Specificity: Expressed in various lymphoid tissues and activated B- and T-lymphocytes, strongly up-regulated in B-cells infected with Epstein-Barr virus and T-cells infected with herpesvirus 6 or 7.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of C-C chemokine receptor type 7 (CCR7).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of C-C chemokine receptor type 7 (CCR7).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of C-C chemokine receptor type 7 (CCR7).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of C-C chemokine receptor type 7 (CCR7).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of C-C chemokine receptor type 7 (CCR7).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of C-C chemokine receptor type 7 (CCR7).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of C-C chemokine receptor type 7 (CCR7).	[5]
Marinol	DM70IK5	Approved	Marinol increases the expression of C-C chemokine receptor type 7 (CCR7).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of C-C chemokine receptor type 7 (CCR7).	[8]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of C-C chemokine receptor type 7 (CCR7).	[9]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of C-C chemokine receptor type 7 (CCR7).	[10]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of C-C chemokine receptor type 7 (CCR7).	[9]
Dinoprostone	DMTYOPD	Approved	Dinoprostone increases the expression of C-C chemokine receptor type 7 (CCR7).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of C-C chemokine receptor type 7 (CCR7).	[12]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of C-C chemokine receptor type 7 (CCR7).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of C-C chemokine receptor type 7 (CCR7).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-C chemokine receptor type 7 (CCR7).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of C-C chemokine receptor type 7 (CCR7).	[15]
GSK618334	DMJPXZ4	Phase 1	GSK618334 decreases the expression of C-C chemokine receptor type 7 (CCR7).	[16]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of C-C chemokine receptor type 7 (CCR7).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of C-C chemokine receptor type 7 (CCR7).	[18]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of C-C chemokine receptor type 7 (CCR7).	[19]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of C-C chemokine receptor type 7 (CCR7).	[20]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of C-C chemokine receptor type 7 (CCR7).	[21]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of C-C chemokine receptor type 7 (CCR7).	[10]
hydroxycitronellal	DMFHCV9	Investigative	hydroxycitronellal increases the expression of C-C chemokine receptor type 7 (CCR7).	[22]

References

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• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [8] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [9] 9-cis-Retinoic acid (9cRA), a retinoid X receptor (RXR) ligand, exerts immunosuppressive effects on dendritic cells by RXR-dependent activation: inhibition of peroxisome proliferator-activated receptor gamma blocks some of the 9cRA activities, and precludes them to mature phenotype development. J Immunol. 2007 May 15;178(10):6130-9. doi: 10.4049/jimmunol.178.10.6130.
• [10] THP-1 monocytes but not macrophages as a potential alternative for CD34+ dendritic cells to identify chemical skin sensitizers. Toxicol Appl Pharmacol. 2009 Apr 15;236(2):221-30.
• [11] Maturation of human monocyte-derived dendritic cells (MoDCs) in the presence of prostaglandin E2 optimizes CD4 and CD8 T cell-mediated responses to protein antigens: role of PGE2 in chemokine and cytokine expression by MoDCs. Int Immunol. 2005 Dec;17(12):1561-72. doi: 10.1093/intimm/dxh335. Epub 2005 Nov 22.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Prediction of the contact sensitizing potential of chemicals using analysis of gene expression changes in human THP-1 monocytes. Toxicol Lett. 2010 Nov 10;199(1):51-9.
• [14] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Phase IIa trial of fingolimod for amyotrophic lateral sclerosis demonstrates acceptable acute safety and tolerability. Muscle Nerve. 2017 Dec;56(6):1077-1084. doi: 10.1002/mus.25733. Epub 2017 Aug 29.
• [17] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
• [20] Redox imbalance induced by contact sensitizers triggers the maturation of dendritic cells. J Invest Dermatol. 2005 Mar;124(3):579-86. doi: 10.1111/j.0022-202X.2005.23624.x.
• [21] Technical advance: Langerhans cells derived from a human cell line in a full-thickness skin equivalent undergo allergen-induced maturation and migration. J Leukoc Biol. 2011 Nov;90(5):1027-33. doi: 10.1189/jlb.0610374. Epub 2011 Jun 22.
• [22] Chemicals with weak skin sensitizing properties can be identified using low-density microarrays on immature dendritic cells. Toxicol Lett. 2007 Nov 1;174(1-3):98-109. doi: 10.1016/j.toxlet.2007.08.015. Epub 2007 Sep 5.