Target Information

Target General Information

Target ID

T30563 (Former ID: TTDR00545)

Target Name

Leukotriene B4 receptor 2 (LTB4R2)

Synonyms

Seven transmembrane receptor BLTR2; Leukotriene B4 receptor BLT2; Leukotriene B(4) receptor BLT2; LTB4-R2; LTB4-R 2; LTB4 receptor JULF2; BLTR2; BLT2R

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Gene Name

LTB4R2

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Human immunodeficiency virus disease [ICD-11: 1C60-1C62]

Renal cell carcinoma [ICD-11: 2C90]

Function

Mediates chemotaxis of granulocytes and macrophages. The response is mediated via G-proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTB4 > 12-epi-LTB4 > LTB5 > LTB3. Low-affinity receptor for leukotrienes including leukotriene B4.

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BioChemical Class

GPCR rhodopsin

UniProt ID

LT4R2_HUMAN

Sequence

MSVCYRPPGNETLLSWKTSRATGTAFLLLAALLGLPGNGFVVWSLAGWRPARGRPLAATL
VLHLALADGAVLLLTPLFVAFLTRQAWPLGQAGCKAVYYVCALSMYASVLLTGLLSLQRC
LAVTRPFLAPRLRSPALARRLLLAVWLAALLLAVPAAVYRHLWRDRVCQLCHPSPVHAAA
HLSLETLTAFVLPFGLMLGCYSVTLARLRGARWGSGRHGARVGRLVSAIVLAFGLLWAPY
HAVNLLQAVAALAPPEGALAKLGGAGQAARAGTTALAFFSSSVNPVLYVFTAGDLLPRAG
PRFLTRLFEGSGEARGGGRSREGTMELRTTPQLKVVGQGRGNGDPGGGMEKDGPEWDL

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 2 Clinical Trial Drugs

LTB4

Drug Info

Phase 2

Human immunodeficiency virus infection

[2]

Biomed 101

Drug Info

Phase 1

Kidney cancer

[3]

Discontinued Drug(s)

[+] 3 Discontinued Drugs

ONO-4057

Drug Info

Discontinued in Phase 2

Inflammatory bowel disease

[4], [5]

CP-105696

Drug Info

Discontinued in Phase 1

Inflammatory bowel disease

[6], [7]

LY-255283

Drug Info

Terminated

Asthma

[8], [9]

Mode of Action

[+] 4 Modes of Action

Inhibitor

[+] 7 Inhibitor drugs

LTB4

Drug Info

[1]

Biomed 101

Drug Info

[1]

CP-105696

Drug Info

[11]

LY-255283

Drug Info

[12]

LY-292728

Drug Info

[13]

(3S,4R)-3-Benzyl-7-isopropyl-chroman-4-ol

Drug Info

[11]

LY-282210

Drug Info

[13]

Modulator

[+] 2 Modulator drugs

ONO-4057

Drug Info

[10]

[3H]LTB4

Drug Info

[20]

Agonist

[+] 6 Agonist drugs

12-epi LTB4

Drug Info

[14]

12-hydroxyheptadecatrienoic acid

Drug Info

[15]

12R-HETE

Drug Info

[16]

12S-HETE

Drug Info

[14]

20-hydroxy-LTB4

Drug Info

[16]

CAY10583

Drug Info

[18]

Antagonist

[+] 3 Antagonist drugs

BIIL 260

Drug Info

[17]

RO5101576

Drug Info

[19]

ZK-158252

Drug Info

[14]

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). Human Similarity Proteins Human Pathway Affiliation

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).

Human Similarity Proteins

Human Pathway Affiliation

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Olfactory receptor 11H12 (OR11H12)	PF13853	24.790 (59/238)	6.10E-04
Olfactory receptor 11H1 (OR11H1)	PF13853	24.375 (39/160)	1.00E-03
Olfactory receptor 11H2 (OR11H2)	PF13853	24.375 (39/160)	2.00E-03

KEGG Pathway	Pathway ID	Affiliated Target
Calcium signaling pathway	hsa04020	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Neuroactive ligand-receptor interaction	hsa04080	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

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Co-Targets

Co-Targets Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 2 KEGG Pathways

Calcium signaling pathway

Neuroactive ligand-receptor interaction

Panther Pathway

[+] 1 Panther Pathways

Inflammation mediated by chemokine and cytokine signaling pathway

Reactome

[+] 2 Reactome Pathways

Leukotriene receptors

G alpha (q) signalling events

WikiPathways

[+] 4 WikiPathways

Gastrin-CREB signalling pathway via PKC and MAPK

GPCR ligand binding

GPCR downstream signaling

GPCRs, Other

Target-Related Models and Studies

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Target Validation

Target Validation Info

Target QSAR Model

References

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REF 1

Diaryl ether/carboxylic acid derivatives of LY255283: Receptor antagonists of leukotriene B4, Bioorg. Med. Chem. Lett. 3(10):1985-1990 (1993).

REF 2

ClinicalTrials.gov (NCT00251537) A Pilot Study of LTB4 in HIV-1 Infected Adults in LTB4 Sweden AB.

REF 3

ClinicalTrials.gov (NCT00004890)Biomed 101 and Interleukin-2 in Treating Patients With Kidney Cancer in National Cancer Institute (NCI).

REF 4

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6157).

REF 5

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003085)

REF 6

REF 7

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800005644)

REF 8

REF 9

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001833)

REF 10

ONO-4057, a novel, orally active leukotriene B4 antagonist: effects on LTB4-induced neutrophil functions. Prostaglandins. 1992 Oct;44(4):261-75.

REF 11

3-Substituted-4-hydroxy-7-chromanylacetic acid derivatives as antagonists of the leukotriene B4 (LTB4) receptor, Bioorg. Med. Chem. Lett. 7(17):2307-2312 (1997).

REF 12

o-phenylphenols: potent and orally active leukotriene B4 receptor antagonists. J Med Chem. 1993 Nov 26;36(24):3978-81.

REF 13

Biphenylyl-substituted xanthones: highly potent leukotriene B4 receptor antagonists. J Med Chem. 1993 Nov 26;36(24):3982-4.

REF 14

Hydroxyeicosanoids bind to and activate the low affinity leukotriene B4 receptor, BLT2. J Biol Chem. 2001 Apr 13;276(15):12454-9.

REF 15

12(S)-Hydroxyheptadeca-5Z, 8E, 10E-trienoic acid is a natural ligand for leukotriene B4 receptor 2. J Exp Med. 2008 Apr 14;205(4):759-66.

REF 16

A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature. 1997 Jun 5;387(6633):620-4.

REF 17

Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis. Ann Rheum Dis. 2007 May;66(5):628-32.

REF 18

Characterization of a mouse second leukotriene B4 receptor, mBLT2: BLT2-dependent ERK activation and cell migration of primary mouse keratinocytes. J Biol Chem. 2005 Jul 1;280(26):24816-23.

REF 19

Effects of LTB4 receptor antagonism on pulmonary inflammation in rodents and non-human primates. Prostaglandins Other Lipid Mediat. 2010 Jun;92(1-4):33-43.

REF 20

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