Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP5FMZ4)

• DOT Name: C-C chemokine receptor type 5 (CCR5)
• Synonyms: C-C CKR-5; CC-CKR-5; CCR-5; CCR5; CHEMR13; HIV-1 fusion coreceptor; CD antigen CD195
• Gene Name: CCR5
• UniProt ID: CCR5_HUMAN
• PDB ID: 2L87; 2MZX; 2RLL; 2RRS; 4MBS; 5UIW; 5YD3; 5YD4; 5YD5; 5YY4; 6FGP; 6MEO; 6MET; 7F1Q; 7F1R; 7F1S; 7NJZ; 7NW3; 7O7F; 8AS2; 8AS3
• Pfam ID: PF00001
• Sequence:
  MDYQVSSPIYDINYYTSEPCQKINVKQIAARLLPPLYSLVFIFGFVGNMLVILILINCKR
  LKSMTDIYLLNLAISDLFFLLTVPFWAHYAAAQWDFGNTMCQLLTGLYFIGFFSGIFFII
  LLTIDRYLAVVHAVFALKARTVTFGVVTSVITWVVAVFASLPGIIFTRSQKEGLHYTCSS
  HFPYSQYQFWKNFQTLKIVILGLVLPLLVMVICYSGILKTLLRCRNEKKRHRAVRLIFTI
  MIVYFLFWAPYNIVLLLNTFQEFFGLNNCSSSNRLDQAMQVTETLGMTHCCINPIIYAFV
  GEKFRNYLLVFFQKHIAKRFCKCCSIFQQEAPERASSVYTRSTGEQEISVGL
• Function: Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Participates in T-lymphocyte migration to the infection site by acting as a chemotactic receptor ; (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) of human immunodeficiency virus-1/HIV-1.
• Tissue Specificity: Highly expressed in spleen, thymus, in the myeloid cell line THP-1, in the promyeloblastic cell line KG-1a and on CD4+ and CD8+ T-cells. Medium levels in peripheral blood leukocytes and in small intestine. Low levels in ovary and lung.
• KEGG Pathway:
  Viral life cycle - HIV-1 (hsa03250)
  Virion - Human immunodeficiency virus (hsa03260)
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  Endocytosis (hsa04144)
  Toxoplasmosis (hsa05145)
  Human cytomegalovirus infection (hsa05163)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Human immunodeficiency virus 1 infection (hsa05170)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  Chemokine receptors bind chemokines (R-HSA-380108)
  G alpha (i) signalling events (R-HSA-418594)
  Interleukin-10 signaling (R-HSA-6783783)
  Binding and entry of HIV virion (R-HSA-173107)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of C-C chemokine receptor type 5 (CCR5).	[1]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of C-C chemokine receptor type 5 (CCR5).	[2]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of C-C chemokine receptor type 5 (CCR5).	[3]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of C-C chemokine receptor type 5 (CCR5).	[4]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of C-C chemokine receptor type 5 (CCR5).	[5]
I3C	DMIGFOR	Phase 3	I3C increases the expression of C-C chemokine receptor type 5 (CCR5).	[6]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of C-C chemokine receptor type 5 (CCR5).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of C-C chemokine receptor type 5 (CCR5).	[1]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-C chemokine receptor type 5 (CCR5).	[8]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of C-C chemokine receptor type 5 (CCR5).	[2]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of C-C chemokine receptor type 5 (CCR5).	[9]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of C-C chemokine receptor type 5 (CCR5).	[10]
Cirsimarin	DMM10TG	Investigative	Cirsimarin decreases the expression of C-C chemokine receptor type 5 (CCR5).	[11]
ISOPENTENYL PYROPHOSPHATE	DMTU05Y	Investigative	ISOPENTENYL PYROPHOSPHATE decreases the expression of C-C chemokine receptor type 5 (CCR5).	[12]

References

• [1] Effects of tobacco compounds on gene expression in fetal lung fibroblasts. Environ Toxicol. 2008 Aug;23(4):423-34.
• [2] 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.
• [3] Cocaine and sigma-1 receptors modulate HIV infection, chemokine receptors, and the HPA axis in the huPBL-SCID model. J Leukoc Biol. 2005 Dec;78(6):1198-203. doi: 10.1189/jlb.0405219. Epub 2005 Oct 4.
• [4] Simvastatin down regulates mRNA expression of RANTES and CCR5 in posttransplant renal recipients with hyperlipidemia. Transplant Proc. 2006 Nov;38(9):2899-904. doi: 10.1016/j.transproceed.2006.08.136.
• [5] 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.
• [6] Aryl hydrocarbon receptor signaling modifies Toll-like receptor-regulated responses in human dendritic cells. Arch Toxicol. 2017 May;91(5):2209-2221.
• [7] 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.
• [8] Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression. Cell Rep. 2015 Sep 29;12(12):1986-96. doi: 10.1016/j.celrep.2015.08.046. Epub 2015 Sep 17.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [11] Flavone cirsimarin impairs cell proliferation, migration, and invasion in MCF-7 cells grown in 2D and 3D models. Toxicol In Vitro. 2022 Sep;83:105416. doi: 10.1016/j.tiv.2022.105416. Epub 2022 Jun 13.
• [12] Patterns of chemokine receptor expression on peripheral blood gamma delta T lymphocytes: strong expression of CCR5 is a selective feature of V delta 2/V gamma 9 gamma delta T cells. J Immunol. 2002 May 15;168(10):4920-9. doi: 10.4049/jimmunol.168.10.4920.