Target Information
Target General Information | Top | |||||
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Target ID |
T63165
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Target Name |
C-C chemokine receptor type 6 (CCR6)
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Synonyms |
C-C CKR-6; CC-CKR-6; CCR-6; Chemokine receptor-like 3; CKR-L3; DRY6; G-protein coupled receptor 29; GPR-CY4; GPRCY4; LARC receptor; CD196
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Gene Name |
CCR6
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Indeterminate colitis [ICD-11: DD72] | |||||
Function |
Receptor for the C-C type chemokine CCL20 (PubMed:9169459). Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels (PubMed:20068036). Although CCL20 is its major ligand it can also act as a receptor for non-chemokine ligands such as beta-defensins (PubMed:25585877). Binds to defensin DEFB1 leading to increase in intracellular calcium ions and cAMP levels. Its binding to DEFB1 is essential for the function of DEFB1 in regulating sperm motility and bactericidal activity (PubMed:25122636). Binds to defensins DEFB4 and DEFB4A/B and mediates their chemotactic effects (PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/ memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases. CCR6-mediated signals are essential for immune responses to microbes in the intestinal mucosa and in the modulation of inflammatory responses initiated by tissue insult and trauma (PubMed:21376174). CCR6 is essential for the recruitment of both the pro-inflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for the normal migration of Th17 cells in Peyers-patches and other related tissue sites of the intestine and plays a role in regulating effector T-cell balance and distribution in inflamed intestine. Plays an important role in the coordination of early thymocyte precursor migration events important for normal subsequent thymocyte precursor development, but is not required for the formation of normal thymic natural regulatory T-cells (nTregs). Required for optimal differentiation of DN2 and DN3 thymocyte precursors. Essential for B-cell localization in the subepithelial dome of Peyers-patches and for efficient B-cell isotype switching to IgA in the Peyers-patches. Essential for appropriate anatomical distribution of memory B-cells in the spleen and for the secondary recall response of memory B-cells (By similarity). Positively regulates sperm motility and chemotaxis via its binding to CCL20 (PubMed:23765988). {ECO:0000250|UniProtKB:O54689, ECO:0000269|PubMed:20068036, ECO:0000269|PubMed:23765988, ECO:0000269|PubMed:25122636, ECO:0000269|PubMed:9169459, ECO:0000303|PubMed:21376174, ECO:0000303|PubMed:25585877}.
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BioChemical Class |
G-protein coupled receptor 1 family
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UniProt ID | ||||||
Sequence |
MSGESMNFSDVFDSSEDYFVSVNTSYYSVDSEMLLCSLQEVRQFSRLFVPIAYSLICVFG
LLGNILVVITFAFYKKARSMTDVYLLNMAIADILFVLTLPFWAVSHATGAWVFSNATCKL LKGIYAINFNCGMLLLTCISMDRYIAIVQATKSFRLRSRTLPRSKIICLVVWGLSVIISS STFVFNQKYNTQGSDVCEPKYQTVSEPIRWKLLMLGLELLFGFFIPLMFMIFCYTFIVKT LVQAQNSKRHKAIRVIIAVVLVFLACQIPHNMVLLVTAANLGKMNRSCQSEKLIGYTKTV TEVLAFLHCCLNPVLYAFIGQKFRNYFLKILKDLWCVRRKYKSSGFSCAGRYSENISRQT SETADNDNASSFTM Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | PF-07054894 | Drug Info | Phase 1 | Inflammatory bowel disease | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Antagonist | [+] 1 Antagonist drugs | + | ||||
1 | PF-07054894 | Drug Info | [1] |
References | Top | |||||
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REF 1 | A Novel C-C Chemoattractant Cytokine (Chemokine) Receptor 6 (CCR6) Antagonist (PF-07054894) Distinguishes between Homologous Chemokine Receptors, Increases Basal Circulating CCR6(+) T Cells, and Ameliorates Interleukin-23-Induced Skin Inflammation. J Pharmacol Exp Ther. 2023 Jul;386(1):80-92. | |||||
REF 2 | ClinicalTrials.gov (NCT05549323) A PHASE 1B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY, SAFETY, AND PHARMACOKINETICS OF ORAL PF-07054894 IN ADULT PARTICIPANTS AGED 18-75 YEARS WITH MODERATE TO SEVERE ULCERATIVE COLITIS. U.S.National Institutes of Health. |
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