Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTC24WT)

• DTT Name: C-C chemokine receptor type 1 (CCR1)
• Synonyms: SCYAR1; RANTES-R; Macrophage inflammatory protein-1 alpha receptor; Macrophage inflammatory protein 1-alpha receptor; MIP-1alpha-R; LD78 receptor; HM145; Chemokine receptor CCR1; CMKR1; CMKBR1; CD191; CCR-1; CC-CKR-1; C-C CKR-1
• Gene Name: CCR1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: CCR1_HUMAN
• TTD ID: T16016
• Sequence:
  METPNTTEDYDTTTEFDYGDATPCQKVNERAFGAQLLPPLYSLVFVIGLVGNILVVLVLV
  QYKRLKNMTSIYLLNLAISDLLFLFTLPFWIDYKLKDDWVFGDAMCKILSGFYYTGLYSE
  IFFIILLTIDRYLAIVHAVFALRARTVTFGVITSIIIWALAILASMPGLYFSKTQWEFTH
  HTCSLHFPHESLREWKLFQALKLNLFGLVLPLLVMIICYTGIIKILLRRPNEKKSKAVRL
  IFVIMIIFFLFWTPYNLTILISVFQDFLFTHECEQSRHLDLAVQVTEVIAYTHCCVNPVI
  YAFVGERFRKYLRQLFHRRVAVHLVKWLPFLSVDRLERVSSTSPSTGEHELSAGF
• Function: 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. Receptor for a C-C type chemokine.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Chemokine signaling 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 DTT

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-817399	DMT8L6P	Rheumatoid arthritis	FA20	Phase 2	[2]
CCX-354	DMSHV9C	Autoimmune diabetes	5A10	Phase 2	[1]
AVE1701	DMJY35M	Rheumatoid arthritis	FA20	Phase 1	[3]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZD4818	DM3VFKM	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[4]
MLN3897	DMRA3EZ	Rheumatoid arthritis	FA20	Discontinued in Phase 2	[3]
COSALANE	DMO3486	N. A.	N. A.	Terminated	[5]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-987306	DMU34BK	Discovery agent	N.A.	Investigative	[6]
BX 471	DM5CGXB	Discovery agent	N.A.	Investigative	[7]
Cosalane derivative	DMSFXJ8	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	4.90E-01	-0.2	-0.18
Chronic obstructive pulmonary disease	CA23	Lung tissue	3.93E-01	0.11	0.22
Chronic obstructive pulmonary disease	CA23	Small airway epithelium	2.85E-04	0.54	0.68

References

• [1] Chemokine receptor CCR1 antagonist CCX354-C treatment for rheumatoid arthritis: CARAT-2, a randomised, placebo controlled clinical trial. Ann Rheum Dis. 2013 Mar;72(3):337-44.
• [2] Discovery of the CCR1 antagonist, BMS-817399, for the treatment of rheumatoid arthritis. J Med Chem. 2014 Sep 25;57(18):7550-64.
• [3] Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96.
• [4] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [5] Inhibition of RANTES/CCR1-mediated chemotaxis by cosalane and related compounds. Bioorg Med Chem Lett. 2001 Jan 8;11(1):59-62.
• [6] cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), a new histamine H4R antagonist that blocks pain... J Med Chem. 2008 Nov 27;51(22):7094-8.
• [7] Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1. J Biol Chem. 2000 Jun 23;275(25):19000-8.