Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVJX54)

• DTT 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
• Gene Name: LTB4R2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: LT4R2_HUMAN
• TTD ID: T30563
• Sequence:
  MSVCYRPPGNETLLSWKTSRATGTAFLLLAALLGLPGNGFVVWSLAGWRPARGRPLAATL
  VLHLALADGAVLLLTPLFVAFLTRQAWPLGQAGCKAVYYVCALSMYASVLLTGLLSLQRC
  LAVTRPFLAPRLRSPALARRLLLAVWLAALLLAVPAAVYRHLWRDRVCQLCHPSPVHAAA
  HLSLETLTAFVLPFGLMLGCYSVTLARLRGARWGSGRHGARVGRLVSAIVLAFGLLWAPY
  HAVNLLQAVAALAPPEGALAKLGGAGQAARAGTTALAFFSSSVNPVLYVFTAGDLLPRAG
  PRFLTRLFEGSGEARGGGRSREGTMELRTTPQLKVVGQGRGNGDPGGGMEKDGPEWDL
• 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.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Leukotriene receptors (R-HSA-391906)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LTB4	DME26RS	Human immunodeficiency virus infection	1C62	Phase 2	[1]
Biomed 101	DMQ9KZW	Kidney cancer	2C90.0	Phase 1	[1]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ONO-4057	DMNEA78	Inflammatory bowel disease	DD72	Discontinued in Phase 2	[2]
CP-105696	DM1C4IN	Inflammatory bowel disease	DD72	Discontinued in Phase 1	[3]
LY-255283	DMFIR0S	Asthma	CA23	Terminated	[4]
LY-292728	DMU24HR	N. A.	N. A.	Terminated	[5]

12 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(3S,4R)-3-Benzyl-7-isopropyl-chroman-4-ol	DMET6IS	Discovery agent	N.A.	Investigative	[3]
12-epi LTB4	DM9JI8C	Discovery agent	N.A.	Investigative	[6]
12-hydroxyheptadecatrienoic acid	DMA2EIK	Discovery agent	N.A.	Investigative	[7]
12R-HETE	DMK0GJ3	Discovery agent	N.A.	Investigative	[8]
12S-HETE	DMBEZ09	Discovery agent	N.A.	Investigative	[6]
20-hydroxy-LTB4	DM84GAQ	Discovery agent	N.A.	Investigative	[8]
BIIL 260	DMU09E4	Discovery agent	N.A.	Investigative	[9]
CAY10583	DMT3MBD	Discovery agent	N.A.	Investigative	[10]
LY-282210	DMBSFDE	Discovery agent	N.A.	Investigative	[5]
RO5101576	DMPXC9L	Discovery agent	N.A.	Investigative	[11]
ZK-158252	DMNMD0J	Discovery agent	N.A.	Investigative	[6]
[3H]LTB4	DMDOJVX	Discovery agent	N.A.	Investigative	[12]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	1.26E-01	0.04	0.15

References

• [1] Diaryl ether/carboxylic acid derivatives of LY255283: Receptor antagonists of leukotriene B4, Bioorg. Med. Chem. Lett. 3(10):1985-1990 (1993).
• [2] ONO-4057, a novel, orally active leukotriene B4 antagonist: effects on LTB4-induced neutrophil functions. Prostaglandins. 1992 Oct;44(4):261-75.
• [3] 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).
• [4] o-phenylphenols: potent and orally active leukotriene B4 receptor antagonists. J Med Chem. 1993 Nov 26;36(24):3978-81.
• [5] Biphenylyl-substituted xanthones: highly potent leukotriene B4 receptor antagonists. J Med Chem. 1993 Nov 26;36(24):3982-4.
• [6] Hydroxyeicosanoids bind to and activate the low affinity leukotriene B4 receptor, BLT2. J Biol Chem. 2001 Apr 13;276(15):12454-9.
• [7] 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.
• [8] A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature. 1997 Jun 5;387(6633):620-4.
• [9] Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis. Ann Rheum Dis. 2007 May;66(5):628-32.
• [10] 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.
• [11] 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.
• [12] 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. (Target id: 268).