Target Information

Target General Information

Target ID

T84981 (Former ID: TTDI02506)

Target Name

C-C chemokine receptor type 7 (CCR7)

Synonyms

MIP3 beta receptor; MIP-3 beta receptor; EpsteinBarr virusinduced Gprotein coupled receptor 1; Epstein-Barr virus-induced G-protein coupled receptor 1; EVI1; EBVinduced Gprotein coupled receptor 1; EBV-induced G-protein coupled receptor 1; EBI1; CMKBR7; CDw197; CD197; CCR-7; CCCKR7; CC-CKR-7; CC chemokine receptor type 7; CC CKR7; C-C CKR-7; BLR2

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Gene Name

CCR7

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Malignant haematopoietic neoplasm [ICD-11: 2B33]

Mature B-cell leukaemia [ICD-11: 2A82]

Function

Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions. Receptor for the MIP-3-beta chemokine.

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BioChemical Class

GPCR rhodopsin

UniProt ID

CCR7_HUMAN

Sequence

MDLGKPMKSVLVVALLVIFQVCLCQDEVTDDYIGDNTTVDYTLFESLCSKKDVRNFKAWF
LPIMYSIICFVGLLGNGLVVLTYIYFKRLKTMTDTYLLNLAVADILFLLTLPFWAYSAAK
SWVFGVHFCKLIFAIYKMSFFSGMLLLLCISIDRYVAIVQAVSAHRHRARVLLISKLSCV
GIWILATVLSIPELLYSDLQRSSSEQAMRCSLITEHVEAFITIQVAQMVIGFLVPLLAMS
FCYLVIIRTLLQARNFERNKAIKVIIAVVVVFIVFQLPYNGVVLAQTVANFNITSSTCEL
SKQLNIAYDVTYSLACVRCCVNPFLYAFIGVKFRNDLFKLFKDLGCLSQEQLRQWSSCRH
IRRSSMSVEAETTTTFSP

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3D Structure

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AlphaFold

HIT2.0 ID

T30A57

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

JBH492

Drug Info

Phase 1

Chronic lymphocytic leukaemia

[2]

CAP-100

Drug Info

Clinical trial

Chronic lymphocytic leukaemia

[3]

Mode of Action

[+] 1 Modes of Action

Antagonist

[+] 1 Antagonist drugs

CAP-100

Drug Info

[4]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
Cytokine-cytokine receptor interaction	hsa04060	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Viral protein interaction with cytokine and cytokine receptor	hsa04061	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Chemokine signaling pathway	hsa04062	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	2	Degree centrality	2.15E-04	Betweenness centrality	8.16E-06
Closeness centrality	1.74E-01	Radiality	1.28E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	7.50E+00	Topological coefficient	5.42E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

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References

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REF 1

Biomarkers in psoriasis and psoriatic arthritis. Ann Rheum Dis. 2013 Apr;72 Suppl 2:ii104-10.

REF 2

ClinicalTrials.gov (NCT04240704) Safety and Preliminary Efficacy of JBH492 Monotherapy in Patients With Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin's Lymphoma (NHL). U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT04704323) An Open Label Phase Ia/b Dose Escalation Followed by Dose Expansion Safety and Tolerability Trial of CAP-100, a Humanized C-C-chemokine Receptor 7 Antibody, Administered as Monotherapy in Subjects With r/r Chronic Lymphocytic Leukemia. U.S.National Institutes of Health.

REF 4

Effect of ibrutinib on CCR7 expression and functionality in chronic lymphocytic leukemia and its implication for the activity of CAP-100, a novel therapeutic anti-CCR7 antibody. Cancer Immunol Immunother. 2022 Mar;71(3):627-636.

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