Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4FC783)

• DOT Name: C-C chemokine receptor type 1 (CCR1)
• Synonyms: C-C CKR-1; CC-CKR-1; CCR-1; CCR1; HM145; LD78 receptor; Macrophage inflammatory protein 1-alpha receptor; MIP-1alpha-R; RANTES-R; CD antigen CD191
• Gene Name: CCR1
• UniProt ID: CCR1_HUMAN
• PDB ID: 7VL8; 7VL9; 7VLA
• Pfam ID: PF00001
• Sequence:
  METPNTTEDYDTTTEFDYGDATPCQKVNERAFGAQLLPPLYSLVFVIGLVGNILVVLVLV
  QYKRLKNMTSIYLLNLAISDLLFLFTLPFWIDYKLKDDWVFGDAMCKILSGFYYTGLYSE
  IFFIILLTIDRYLAIVHAVFALRARTVTFGVITSIIIWALAILASMPGLYFSKTQWEFTH
  HTCSLHFPHESLREWKLFQALKLNLFGLVLPLLVMIICYTGIIKILLRRPNEKKSKAVRL
  IFVIMIIFFLFWTPYNLTILISVFQDFLFTHECEQSRHLDLAVQVTEVIAYTHCCVNPVI
  YAFVGERFRKYLRQLFHRRVAVHLVKWLPFLSVDRLERVSSTSPSTGEHELSAGF
• Function: Receptor for a C-C type chemokine. Binds to MIP-1-alpha, MIP-1-delta, RANTES, and MCP-3 and, less efficiently, to MIP-1-beta or MCP-1 and subsequently transduces a signal by increasing the intracellular calcium ions level. Responsible for affecting stem cell proliferation.
• Tissue Specificity: Widely expressed in different hematopoietic cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  Human cytomegalovirus infection (hsa05163)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Interleukin-10 signaling (R-HSA-6783783)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

13 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 1 (CCR1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of C-C chemokine receptor type 1 (CCR1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-C chemokine receptor type 1 (CCR1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of C-C chemokine receptor type 1 (CCR1).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of C-C chemokine receptor type 1 (CCR1).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of C-C chemokine receptor type 1 (CCR1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of C-C chemokine receptor type 1 (CCR1).	[7]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of C-C chemokine receptor type 1 (CCR1).	[8]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of C-C chemokine receptor type 1 (CCR1).	[9]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of C-C chemokine receptor type 1 (CCR1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of C-C chemokine receptor type 1 (CCR1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of C-C chemokine receptor type 1 (CCR1).	[11]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of C-C chemokine receptor type 1 (CCR1).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] Pattern of expression of apoptosis and inflammatory genes in humans exposed to arsenic and/or fluoride. Sci Total Environ. 2010 Jan 15;408(4):760-7. doi: 10.1016/j.scitotenv.2009.11.016. Epub 2009 Dec 4.
• [7] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [8] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [9] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [10] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [11] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.