CYSLTR1

Summary

CYSLTR1 (cysteinyl leukotriene receptor 1, HGNC:17451) is a protein-coding gene on chromosome Xq21.1, encoding Cysteinyl leukotriene receptor 1 (Q9Y271). Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma.

This gene encodes a member of the G-protein coupled receptor 1 family. The encoded protein is a receptor for cysteinyl leukotrienes, and is involved in mediating bronchoconstriction via activation of a phosphatidylinositol-calcium second messenger system. Activation of the encoded receptor results in contraction and proliferation of bronchial smooth muscle cells, eosinophil migration, and damage to the mucus layer in the lung. Upregulation of this gene is associated with asthma and dysregulation may also be implicated in cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 10800 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 62 total
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006639

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17451
Approved symbol	CYSLTR1
Name	cysteinyl leukotriene receptor 1
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Aliases	CysLT1, CysLT(1), CYSLT1R
Ensembl gene	ENSG00000173198
Ensembl biotype	protein_coding
OMIM	300201
Entrez	10800

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000373304, ENST00000493254, ENST00000614798, ENST00000856868, ENST00000955226, ENST00000955227

RefSeq mRNA: 4 — MANE Select: NM_006639 NM_001282186, NM_001282187, NM_001282188, NM_006639

CCDS: CCDS14439

Canonical transcript exons

ENST00000373304 — 3 exons

Exon	Start	End
ENSE00001317051	78283454	78283540
ENSE00001460073	78271468	78273773
ENSE00001941719	78327305	78327611

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 93.62.

FANTOM5 (CAGE): breadth broad, TPM avg 3.9495 / max 150.5259, expressed in 413 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199811	1.5778	285
199809	0.8868	199
199810	0.6513	181
199812	0.3652	157
199814	0.1604	77
199815	0.1459	72
199808	0.0845	36
199813	0.0777	44

Top tissues by expression

266 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.62	gold quality
monocyte	CL:0000576	90.30	gold quality
mononuclear cell	CL:0000842	89.94	gold quality
leukocyte	CL:0000738	89.66	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.69	gold quality
lower esophagus	UBERON:0013473	84.57	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.85	gold quality
superficial temporal artery	UBERON:0001614	83.14	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.25	gold quality
granulocyte	CL:0000094	80.53	gold quality
bone marrow	UBERON:0002371	79.18	gold quality
lymph node	UBERON:0000029	78.91	gold quality
blood	UBERON:0000178	77.91	gold quality
palpebral conjunctiva	UBERON:0001812	77.64	gold quality
calcaneal tendon	UBERON:0003701	76.54	gold quality
colonic epithelium	UBERON:0000397	76.49	gold quality
gall bladder	UBERON:0002110	76.34	gold quality
tendon	UBERON:0000043	75.77	gold quality
rectum	UBERON:0001052	75.51	gold quality
spleen	UBERON:0002106	75.21	gold quality
oral cavity	UBERON:0000167	74.92	gold quality
bone marrow cell	CL:0002092	73.98	gold quality
tonsil	UBERON:0002372	73.79	gold quality
vermiform appendix	UBERON:0001154	73.43	gold quality
esophagus	UBERON:0001043	73.33	gold quality
mucosa of stomach	UBERON:0001199	73.19	gold quality
trabecular bone tissue	UBERON:0002483	72.46	gold quality
smooth muscle tissue	UBERON:0001135	72.04	gold quality
caecum	UBERON:0001153	70.98	gold quality
parietal pleura	UBERON:0002400	70.29	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	13.67
E-MTAB-5061	yes	13.46
E-ANND-3	yes	8.15
E-CURD-135	no	1517.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT6

miRNA regulators (miRDB)

101 targeting CYSLTR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358

Literature-anchored findings (GeneRIF, showing 40)

• interaction of CysLTs and CysLT(1) on eosinophils has the potential to play a prominent role in the pathophysiology of asthma. (PMID:12373000)
• CysLT1R expression, up-regulated by IL-13 and leukotriene C4, may contribute to eotaxin production by lung fibroblasts. (PMID:12682264)
• CysLT1 receptor upregulation by TGF-beta and IL-13 is associated with bronchial smooth muscle cell proliferation in response to LTD4. (PMID:12743568)
• Arachidonic acid inhibits cysteinyl-leukotriene receptor activation in human pulmonary vessels (PMID:12751740)
• upregulated in colon cancer; affecting survival (PMID:12751768)
• the importance of increased CysLT signaling in airway smooth muscle function (PMID:15064240)
• CysLT1R as the first G protein-coupled receptor identified to date in which protein kinase C is the principal regulator of both rapid agonist-dependent internalization. (PMID:15590629)
• CysLT 1 expression predominates on inflammatory leukocytes in aspirin-sensitive rhinosinusitis. Effects of cysteinyl leukotrienes on glands and epithelium may be mediated predominantly through cysLT 2. Potentially important therapeutic implications. (PMID:15696087)
• There is increased nuclear localization of the CysLT(1) receptor in colorectal adenocarcinomas. (PMID:15705869)
• upregulation of cysteinyl leukotriene-1 receptor is associated with asthma (PMID:16123393)
• Leukotriene D4, via the CysLT1 receptor, can transcriptionally activate IL-8 production, with involvement of the transcription factors p50, p65, Fos, and Jun. (PMID:16809637)
• The 927T>C CYSLTR1 SNP was analyzed by direct sequencing after PCR amplification in childres with asthma and atopic dermatitis. (PMID:16846449)
• In the group of male patients, the C allele of 927T> C CYSLTRI was more common among patients with asthma than controls (PMID:17153879)
• Desensitization of the CysLT1R is the principal mechanism by which PKC regulates the functional consequences of its desensitization in tracheea smooth muscle. (PMID:17392478)
• analysis of polymorphism and differential regulation of CYSLTR1 transcription in human airway smooth muscle and monocytes (PMID:17406065)
• Overexpression of cysteinyl LT1 receptor is associated with prostate cancer (PMID:17549353)
• discovered a CysLT1 G300S variant that is carried with a significantly higher frequency in atopics and asthmatics from the Tristan da Cunha population (PMID:17558309)
• CysLTR1 polymorphism may contribute to development of the aspirin-intolerant asthma phenotype and can be used as a genetic marker for differentiating two major aspirin hypersensitivity phenotypes. (PMID:17641958)
• CysLT2R signaling leads to terminal differentiation of colon carcinoma cells and growth inhibition, and its expression is relatively high in less malignant forms of colon cancer. (PMID:17909024)
• CysLTR1 promoter polymorphism is a useful genetic marker for predicting leukotriene receptor antagonist requirement in aspirin intolerant asthma patienets (PMID:17924829)
• CysLT1R and CysLT2R expression in monocytes can be regulated by CysLT itself and T(H)2 cytokines at the transcriptional level. (PMID:17941281)
• Our data show that CysLTs acting through CysLTR(1) can significantly influence the activation and migration of human monocytes. (PMID:18028998)
• STAT-1 is involved in the signal transduction mechanism associated with cysteinyl leukotriene receptor 1 activation, supporting the hypothesis that it may represent a key transduction pathway leading to enhanced eosinophil adhesiveness. (PMID:18305014)
• CysLT1 is involved in remodeling processes through modulation of furin transcription. (PMID:18323532)
• Report the long-term effect of Helicobacter pylori eradication on COX-1/2, 5-LOX and leukotriene receptors in patients with a risk gastritis phenotype–a link to gastric carcinogenesis. (PMID:18571838)
• Results demonstrate that cysteinyl leucotrienes cause contraction in the human and guinea-pig oesophagus, which is mediated by the cysteinyl leucotriene receptor type 1. (PMID:18651869)
• SNP rs320995 in the cysteinyl leukotriene receptor 1 gene was associated with risk of asthma (PMID:18829683)
• The combined study of polymorphisms in genes of the leukotriene pathway could explain the differences observed in the studies reported on polymorphism -444A < C LTC4S individually analysed. (PMID:19080797)
• The most potent CysLT(1) ligand, LTD(4), rapidly and significantly up-regulated alpha(4)beta(1) and alpha(5)beta(1) integrin-dependent adhesion of both primitive and committed hematopoietic progenitor cells (PMID:19454674)
• CYSLTR1 polymorphism previously shown to affect the gene transcription in vitro might influence the risk of atopy in the female white population with suggestive evidence of heterozygote vigor. (PMID:19733299)
• Genetic variants of CYSLTR1 promoter might be associated with gender specific expression of CysLT1 alternative transcripts in patients with asthma. (PMID:20003473)
• Data show functional expression of CysLT1 and 2 receptors on human platelets and demonstrate that CysLTs induced the release of significant amounts of RANTES, which suggests a novel role for human platelets in CysLT-mediated allergic inflammation. (PMID:20433311)
• CysLT1-R expression following allergen provocation in asthma and allergic rhinitis. (PMID:20462748)
• upon ligand activation, CysLT(1)R is tyrosine-phosphorylated and released from heterodimers with CysLT(2)R and, subsequently, internalizes from the plasma membrane to the nuclear membrane in a clathrin-, arrestin-3-, and Rab-5-dependent manner (PMID:21203429)
• cysteinyl-leukotriene receptors are differently expressed in fibroblast from peripheral versus central airways in asthmatics and healthy controls. (PMID:21596548)
• Data suggest that CysLT1 induces chemokine-like effects, supports accumulation and survival of chronic lymphocytic leukemia (CLL) cells in the bone marrow and thus represents a potential treatment target. (PMID:21936770)
• A role of nuclear CysLT(1) receptor signaling in vascular smooth muscle cells inducing gene expression patterns associated with atherosclerosis. (PMID:22527886)
• increased expression in tonsillar tissues of Chinese children with sleep-disordered breathing (PMID:22634478)
• Bronchial mucosal CysLT1 receptor-positive inflammatory cells are present in the bronchial mucosa in COPD in greatest number in those experiencing a severe exacerbation. (PMID:22871757)
• CysLT(1) receptors in endothelial cells translocate to the nucleus in a ligand-independent manner after ischemic insult in vitro, and it is involved in the ischemic injury. (PMID:23085741)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cysltr1	ENSDARG00000058246
mus_musculus	Cysltr1	ENSMUSG00000052821
rattus_norvegicus	Cysltr1	ENSRNOG00000037845
caenorhabditis_elegans		WBGENE00016570

Paralogs (16): P2RY10 (ENSG00000078589), GPR18 (ENSG00000125245), F2RL3 (ENSG00000127533), GPR55 (ENSG00000135898), LPAR6 (ENSG00000139679), GPR65 (ENSG00000140030), GPR17 (ENSG00000144230), LPAR4 (ENSG00000147145), CYSLTR2 (ENSG00000152207), F2RL2 (ENSG00000164220), F2RL1 (ENSG00000164251), GPR4 (ENSG00000177464), GPR35 (ENSG00000178623), F2R (ENSG00000181104), P2RY8 (ENSG00000182162), GPR20 (ENSG00000204882)

Protein

Protein identifiers

Cysteinyl leukotriene receptor 1 — Q9Y271 (reviewed: Q9Y271)

Alternative names: Cysteinyl leukotriene D4 receptor, G-protein coupled receptor HG55, HMTMF81

All UniProt accessions (1): Q9Y271

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma. Stimulation by LTD4 results in the contraction and proliferation of smooth muscle, edema, eosinophil migration and damage to the mucus layer in the lung. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTD4 » LTE4 = LTC4 » LTB4.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed, with highest levels in spleen and peripheral blood leukocytes. Lower expression in several tissues, such as lung (mostly in smooth muscle bundles and alveolar macrophages), placenta, small intestine, pancreas, colon and heart.

Miscellaneous. Selective antagonists, such as montelukast (Singulair), zafirlukast (Accolate) and pranlukast (Onon), are used in the treatment of the asthma crisis.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (4): NP_001269115, NP_001269116, NP_001269117, NP_006630* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR004071	Cyst_leuk_rcpt	Family
IPR013310	CLT1_recept	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (38 total): helix 14, topological domain 8, transmembrane region 7, glycosylation site 4, turn 2, chain 1, disulfide bond 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6RZ5	X-RAY DIFFRACTION	2.53
6RZ4	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y271-F1	85.79	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 96–173

Glycosylation sites (4): 6, 169, 180, 262

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-391906	Leukotriene receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-9664535	LTC4-CYSLTR mediated IL4 production
R-HSA-9679191	Potential therapeutics for SARS

MSigDB gene sets: 210 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, REACTOME_EICOSANOID_LIGAND_BINDING_RECEPTORS, SABATES_COLORECTAL_ADENOMA_SIZE_DN, RODRIGUES_NTN1_TARGETS_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, AACWWCAANK_UNKNOWN, GOBP_REACTIVE_OXYGEN_SPECIES_BIOSYNTHETIC_PROCESS, GOBP_TAXIS, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_ENDOTHELIUM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOMF_PEPTIDE_RECEPTOR_ACTIVITY

GO Biological Process (14): inflammatory response to antigenic stimulus (GO:0002437), endothelium development (GO:0003158), calcium ion transport (GO:0006816), chemotaxis (GO:0006935), defense response (GO:0006952), cell surface receptor signaling pathway (GO:0007166), positive regulation of cytosolic calcium ion concentration (GO:0007204), neuropeptide signaling pathway (GO:0007218), respiratory gaseous exchange by respiratory system (GO:0007585), establishment of localization in cell (GO:0051649), reactive oxygen species biosynthetic process (GO:1903409), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), leukotriene signaling pathway (GO:0061737)

GO Molecular Function (4): cysteinyl leukotriene receptor activity (GO:0001631), galanin receptor activity (GO:0004966), leukotriene receptor activity (GO:0004974), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Eicosanoid ligand-binding receptors	1
GPCR downstream signalling	1
Anti-inflammatory response favouring Leishmania parasite infection	1
SARS-CoV Infections	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
signal transduction	2
inflammatory response	1
immune response	1
epithelium development	1
metal ion transport	1
response to chemical	1
taxis	1
response to stress	1
regulation of biological quality	1
multicellular organismal process	1
establishment of localization	1
cellular localization	1
biosynthetic process	1
reactive oxygen species metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
leukotriene receptor activity	1
neuropeptide receptor activity	1
icosanoid receptor activity	1
leukotriene signaling pathway	1
transmembrane signaling receptor activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CYSLTR1	LTC4S	Q16873	946
CYSLTR1	ALOX5AP	P20292	784
CYSLTR1	ALOX5	P09917	762
CYSLTR1	LTA4H	P09960	694
CYSLTR1	TBXA2R	P21731	601
CYSLTR1	LTB4R2	Q9NPC1	555
CYSLTR1	P2RY12	Q9H244	552
CYSLTR1	TBXAS1	P24557	548
CYSLTR1	GNAQ	P50148	526
CYSLTR1	LTB4R	Q15722	516
CYSLTR1	IL13	P35225	507
CYSLTR1	IL5	P05113	506
CYSLTR1	PTGDR2	Q9Y5Y4	503
CYSLTR1	OXGR1	Q96P68	500
CYSLTR1	PTPRE	P23469	497

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CYSLTR2	CYSLTR1	psi-mi:“MI:2364”(proximity)	0.470
CYSLTR1	CYSLTR2	psi-mi:“MI:0915”(physical association)	0.470
CYSLTR1	RAMP1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): CYSLTR2 (FRET), CYSLTR2 (Affinity Capture-Western), CYSLTR1 (Affinity Capture-Western), CYSLTR2 (Co-localization), CYSLTR1 (Affinity Capture-Western), DNAH5 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1A5S3, A5PLE7, B0UXR0, B5X337, D4A7K7, O00398, O18982, O54689, O97663, P21556, P25105, P25106, P32249, P35351, P35374, P46002, P47749, P47900, P48042, P49650, P49651, P49685, P50052, P51684, P56412, Q1RMI1, Q28929, Q2NNR5, Q3U507, Q3U6B2, Q3UJF0, Q5ZI82, Q61038, Q62035, Q8BZR0, Q8IYL9, Q8K1Z6, Q924T8, Q95N02, Q95N03

Diamond homologs: A5PLE7, B0UXR0, B5X337, D4A7K7, F1MV99, O08858, O35210, O35811, O77590, O88634, P11613, P21556, P25025, P25095, P25104, P25106, P26824, P29089, P29754, P29755, P30555, P30556, P30937, P30938, P31391, P32249, P32250, P32300, P33396, P33535, P34976, P35346, P35366, P35372, P35373, P35383, P41143, P41231, P41232, P42866

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CYSLTR1	“up-regulates activity”	GNAI1	binding
CYSLTR1	“up-regulates activity”	GNAI3	binding
CYSLTR1	“up-regulates activity”	GNAQ	binding
CYSLTR1	“up-regulates activity”	GNA14	binding
CYSLTR1	“up-regulates activity”	GNA15	binding
“leukotriene D4(1-)”	“up-regulates activity”	CYSLTR1	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

62 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

506 predictions. Top by Δscore:

Variant	Effect	Δscore
X:78327300:CTTA:C	donor_loss	1.0000
X:78327301:TTA:T	donor_loss	1.0000
X:78327302:TACCT:T	donor_loss	1.0000
X:78327303:A:AC	donor_gain	1.0000
X:78327304:C:CC	donor_gain	1.0000
X:78327304:CCTG:C	donor_gain	1.0000
X:78327334:T:A	donor_gain	0.9900
X:78283467:TGGAG:T	donor_gain	0.9400
X:78279485:ATAC:A	donor_gain	0.9300
X:78327301:TTAC:T	donor_gain	0.9200
X:78273771:TGCC:T	acceptor_loss	0.9100
X:78273772:GCCT:G	acceptor_loss	0.9100
X:78273773:CCTA:C	acceptor_loss	0.9100
X:78273774:CTAT:C	acceptor_loss	0.9100
X:78273775:T:A	acceptor_loss	0.9100
X:78327302:TAC:T	donor_gain	0.9100
X:78327303:A:T	donor_gain	0.9000
X:78273783:A:C	acceptor_loss	0.8900
X:78327304:CCT:C	donor_gain	0.8900
X:78283539:CG:C	acceptor_gain	0.8600
X:78327304:C:G	donor_gain	0.8600
X:78273774:C:CC	acceptor_gain	0.8500
X:78327294:AGTCT:A	donor_gain	0.8500
X:78283536:CCACG:C	acceptor_gain	0.8400
X:78283537:CACG:C	acceptor_gain	0.8400
X:78283537:CACGC:C	acceptor_gain	0.8400
X:78273769:TGTGC:T	acceptor_gain	0.8300
X:78327300:CTT:C	donor_gain	0.8300
X:78327303:AC:A	donor_gain	0.8200
X:78327304:CC:C	donor_gain	0.8200

AlphaMissense

2248 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:78272989:C:G	R253P	0.998
X:78273004:G:C	P248R	0.998
X:78273004:G:T	P248Q	0.998
X:78273229:C:G	C173S	0.998
X:78273230:A:T	C173S	0.998
X:78273393:G:C	S118R	0.998
X:78273393:G:T	S118R	0.998
X:78273395:T:G	S118R	0.998
X:78273009:G:C	F246L	0.997
X:78273009:G:T	F246L	0.997
X:78273011:A:G	F246L	0.997
X:78273230:A:G	C173R	0.997
X:78273460:C:G	C96S	0.997
X:78273461:A:T	C96S	0.997
X:78273480:C:A	W89C	0.997
X:78273480:C:G	W89C	0.997
X:78273482:A:G	W89R	0.997
X:78273482:A:T	W89R	0.997
X:78273012:A:C	S245R	0.996
X:78273012:A:T	S245R	0.996
X:78273014:T:G	S245R	0.996
X:78273305:A:G	W148R	0.996
X:78273305:A:T	W148R	0.996
X:78273541:T:G	D69A	0.996
X:78272896:G:T	A284D	0.995
X:78273005:G:A	P248S	0.995
X:78273021:A:C	F242L	0.995
X:78273021:A:T	F242L	0.995
X:78273023:A:G	F242L	0.995
X:78273282:A:C	S155R	0.995

dbSNP variants (sampled 300 via entrez): RS1000021866 (X:78312845 A>G), RS1000033134 (X:78312534 T>C), RS1000148060 (X:78315044 G>A), RS1000164127 (X:78303619 T>C), RS1000270998 (X:78321074 G>A,C), RS1000325173 (X:78304183 T>G), RS1000445494 (X:78329522 C>A,T), RS1000624853 (X:78315471 G>A), RS1000654844 (X:78306985 A>C), RS1000797240 (X:78274264 C>G), RS1000815224 (X:78298472 T>C), RS1000825946 (X:78296546 A>C), RS1000838731 (X:78286285 T>TA), RS1000867722 (X:78298064 A>G), RS1000889930 (X:78294405 G>A,C)

Disease associations

OMIM: gene MIM:300201 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006031_15	Potassium levels	3.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009283	potassium measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1798 (SINGLE PROTEIN), CHEMBL2094254 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 492,045 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1200681	MONTELUKAST SODIUM	4	10,913
CHEMBL21333	PRANLUKAST	4	12,755
CHEMBL411	DIETHYLSTILBESTROL	4	353,912
CHEMBL603	ZAFIRLUKAST	4	23,220
CHEMBL787	MONTELUKAST	4	26,700
CHEMBL22016	ABLUKAST	2	1,780
CHEMBL22776	POBILUKAST	2	2,150
CHEMBL280481	VERLUKAST	2	2,491
CHEMBL3597634	GEMILUKAST	2	104
CHEMBL162358	TOMELUKAST	2	1,180
CHEMBL17344	RITOLUKAST	2	515

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: gpcr — Leukotriene receptors

Most potent curated ligand interactions (21 total), top 21:

Ligand	Action	Affinity	Parameter
[3H]LTD4	Agonist	10.7	pKd
[3H]ICI-198615	Antagonist	10.6	pKd
pranlukast	Antagonist	10.0	pIC50
ICI198615	Antagonist	9.7	pKi
compound 13e [PMID: 31811124]	Antagonist	9.0	pIC50
triple modulator 10 [PMID: 29878767]	Antagonist	8.7	pA2
SR2640	Antagonist	8.7	pKi
montelukast	Antagonist	8.64	pIC50
sulukast	Antagonist	8.3	pKi
LTD4	Full agonist	8.05	pIC50
MK-571	Antagonist	8.0	pIC50
verlukast	Antagonist	7.97	pIC50
iralukast	Antagonist	7.8	pKi
zafirlukast	Antagonist	7.7	pIC50
pobilukast	Antagonist	7.1	pKi
compound 15b [PMID: 31811124]	Antagonist	6.92	pIC50
LTC4	Full agonist	6.46	pIC50
LTE4	Partial agonist	6.41	pEC50
BayCysLT2	Antagonist	6.4	pA2
N-methyl LTC4	Partial agonist	5.7	pEC50
BAYu9773	Antagonist	5.3	pIC50

Binding affinities (BindingDB)

3 measured of 5 human assays (6 total across all organisms); most potent 3 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
cyclopentyl 3-(2-methoxy-4-((o-tolylsulfonyl)carbamoyl)benzyl)-1-methylindole-5-carbamate	KI	0.26 nM
NSC_5311297	KI	2.3 nM
3-(((3-(2-(7-chloroquinoline-2-yl)ethenyl)phenyl)((3-dimethylamino-3-oxopropyl)thio)methyl)thio)propanoic acid	KI	10.4 nM

ChEMBL bioactivities

740 potent at pChembl≥5 of 761 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.51	IC50	0.031	nM	CHEMBL354129
10.36	IC50	0.044	nM	PRANLUKAST
10.22	IC50	0.06	nM	CHEMBL171021
10.10	Kd	0.07943	nM	CHEMBL48435
10.00	Ki	0.1	nM	CHEMBL299837
10.00	Kd	0.1	nM	CHEMBL4280282
9.96	IC50	0.11	nM	CHEMBL169790
9.85	IC50	0.14	nM	CHEMBL354530
9.80	IC50	0.16	nM	CHEMBL170191
9.77	IC50	0.17	nM	CHEMBL343934
9.72	IC50	0.19	nM	CHEMBL344180
9.72	IC50	0.19	nM	CHEMBL343934
9.70	IC50	0.2	nM	CHEMBL178221
9.70	Ki	0.2	nM	CHEMBL89768
9.70	Ki	0.2	nM	CHEMBL48927
9.70	Ki	0.2	nM	ICI-198615
9.70	IC50	0.2	nM	CHEMBL313187
9.68	IC50	0.21	nM	CHEMBL139757
9.66	IC50	0.22	nM	CHEMBL3597618
9.62	IC50	0.24	nM	CHEMBL313195
9.60	Ki	0.25	nM	CHEMBL299093
9.60	Ki	0.25	nM	CHEMBL51585
9.60	IC50	0.25	nM	CHEMBL344180
9.59	IC50	0.26	nM	ZAFIRLUKAST
9.59	IC50	0.26	nM	CHEMBL314237
9.54	Ki	0.29	nM	LEUKOTRIENE D4
9.54	IC50	0.29	nM	CHEMBL414885
9.52	Ki	0.3	nM	CHEMBL297952
9.52	Ki	0.3	nM	CHEMBL296821
9.52	Ki	0.3	nM	ZAFIRLUKAST
9.52	IC50	0.3	nM	CHEMBL368290
9.52	Ki	0.3	nM	CHEMBL412056
9.52	Ki	0.3	nM	CHEMBL50562
9.52	Ki	0.3	nM	CHEMBL300096
9.52	Ki	0.3	nM	CHEMBL49944
9.49	IC50	0.32	nM	CHEMBL3597617
9.47	IC50	0.34	nM	CHEMBL341603
9.47	IC50	0.34	nM	CHEMBL86302
9.47	IC50	0.34	nM	CHEMBL87337
9.47	IC50	0.34	nM	CHEMBL315973
9.46	IC50	0.35	nM	CHEMBL140381
9.43	IC50	0.37	nM	CHEMBL172889
9.43	IC50	0.37	nM	CHEMBL86302
9.42	IC50	0.38	nM	CHEMBL313187
9.40	IC50	0.4	nM	CHEMBL425675
9.38	IC50	0.42	nM	CHEMBL316170
9.38	IC50	0.42	nM	CHEMBL314237
9.38	IC50	0.42	nM	CHEMBL85633
9.38	IC50	0.42	nM	CHEMBL343934
9.37	IC50	0.43	nM	MONTELUKAST

PubChem BioAssay actives

672 with measured affinity, of 1443 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[(E)-hept-2-enoxy]-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	<0.0001	uM
N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]-4-(4-phenylbutoxy)benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	<0.0001	uM
Zafirlukast	1410776: Antagonist potency at human CysLT1R expressed in African green monkey COS7 cells assessed as inhibition of LTD4-induced Ca2+ levels after 60 mins by fura-2/AM-fluorescence based spectrofluorimetry	kd	<0.0001	uM
4-[(E)-oct-2-enoxy]-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0001	uM
4-oct-7-enoxy-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0001	uM
4-oct-2-ynoxy-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0001	uM
cyclopentyl N-[3-[[4-[(3-chlorophenyl)sulfonylcarbamoyl]-2-methoxyphenyl]methyl]-1-methylindol-5-yl]carbamate	1410776: Antagonist potency at human CysLT1R expressed in African green monkey COS7 cells assessed as inhibition of LTD4-induced Ca2+ levels after 60 mins by fura-2/AM-fluorescence based spectrofluorimetry	kd	0.0001	uM
cyclopentyl N-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-methylindol-5-yl]carbamate	1410776: Antagonist potency at human CysLT1R expressed in African green monkey COS7 cells assessed as inhibition of LTD4-induced Ca2+ levels after 60 mins by fura-2/AM-fluorescence based spectrofluorimetry	kd	0.0001	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-(cyclobutylcarbamoylamino)-1-methylindazol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0001	uM
cyclopentyl N-[1-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]indazol-6-yl]carbamate	55075: In vitro binding affinity against cysteinyl leukotriene D4 receptor from guinea pig lung membrane	ki	0.0002	uM
4-[1-(carboxymethyl)-7-[2-[4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl]ethynyl]-2-methylindol-3-yl]butanoic acid	1236046: Antagonist activity at human CysLT1 expressed in CHOK1 cells assessed as inhibition of LTD4-induced calcium mobilization preincubated for 30 mins prior to LTD4 addition measured after 1 hr by Fura 2-AM dye-based fluorescence assay	ic50	0.0002	uM
4-[(2E)-octa-2,7-dienoxy]-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0002	uM
cyclopentyl N-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-(2-methoxyethyl)indol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0002	uM
sodium 3-[[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-[3-(dimethylamino)-3-oxopropyl]sulfanylmethyl]sulfanylpropanoate	55237: Binding affinity against Cysteinyl leukotriene D4 receptor	ki	0.0002	uM
2-[1-[[(1R)-1-[3-[(E)-2-(5,7-dihydrothieno[3,4-b]pyridin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0002	uM
2-[1-[[(1R)-1-[3-[(E)-2-(7,7-dimethyl-6,8-dihydro-5H-quinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102663: In vitro inhibition of [3H]LTD4 binding to LTD4 receptor of guinea pig lung membrane with human serum albumin (HSA).	ic50	0.0002	uM
2-[1-[[(1R)-3-[2-(2-hydroxypropan-2-yl)phenyl]-1-[3-[(E)-2-(5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0002	uM
2,2-diethyl-4-[3-[(7-fluoroquinolin-2-yl)methoxy]anilino]-4-oxobutanoic acid	102803: In vitro for antagonistic activity against LTD4 receptor in guinea pig ileum	ic50	0.0002	uM
3-[1-(carboxymethyl)-7-[2-[4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl]ethynyl]-2-methylindol-3-yl]propanoic acid	1236046: Antagonist activity at human CysLT1 expressed in CHOK1 cells assessed as inhibition of LTD4-induced calcium mobilization preincubated for 30 mins prior to LTD4 addition measured after 1 hr by Fura 2-AM dye-based fluorescence assay	ic50	0.0003	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-[(2-cyclopentylacetyl)amino]-1-methylindol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
cyclopentyl N-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-methylindazol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
cyclopentyl N-[3-[[2-methoxy-4-[(2-methylphenyl)sulfonylcarbamoyl]phenyl]methyl]-1-methylindazol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
cyclopentyl N-[3-[[4-[(2-chlorophenyl)sulfonylcarbamoyl]-2-methoxyphenyl]methyl]-1-methylindazol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
cyclopentyl N-[3-[[4-[(2-bromophenyl)sulfonylcarbamoyl]-2-methoxyphenyl]methyl]-1-methylindazol-5-yl]carbamate	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
4-[[5-[(2-cyclopentylacetyl)amino]-1-methylindazol-3-yl]methyl]-3-methoxy-N-(2-methylphenyl)sulfonylbenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-[(2-cyclopentylacetyl)amino]-1-methylindazol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-[(2-cyclohexylacetyl)amino]-1-methylindazol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0003	uM
2-[1-[[(1R)-1-[3-[(E)-2-(7,7-dimethyl-5,6-dihydrocyclopenta[b]pyridin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102663: In vitro inhibition of [3H]LTD4 binding to LTD4 receptor of guinea pig lung membrane with human serum albumin (HSA).	ic50	0.0003	uM
2-[1-[[(1R)-1-[3-[(E)-2-(6,6-dimethyl-5,7-dihydrocyclopenta[b]pyridin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0003	uM
2,2-diethyl-4-[3-[(5-fluoroquinolin-2-yl)methoxy]anilino]-4-oxobutanoic acid	102803: In vitro for antagonistic activity against LTD4 receptor in guinea pig ileum	ic50	0.0003	uM
(5S,6R,7E,9E,11Z,14Z)-6-[(2R)-2-amino-3-(carboxymethylamino)-3-oxopropyl]sulfanyl-5-hydroxyicosa-7,9,11,14-tetraenoic acid	751668: Displacement of [3H]LTD4 from human recombinant cysteinyl leukotriene receptor 1 expressed in CHOK1 cells after 30 mins	ki	0.0003	uM
4-(4-phenylbutoxy)-N-[3-(2H-tetrazol-5-yl)-2,3-dihydro-1,4-benzodioxin-5-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0004	uM
2-[1-[[(1R)-1-[3-[(E)-2-(6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102799: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of DMSO differentiated human U937 cell membranes	ic50	0.0004	uM
2,2-diethyl-4-[3-[(E)-2-(7-fluoroquinolin-2-yl)ethenyl]anilino]-4-oxobutanoic acid	102803: In vitro for antagonistic activity against LTD4 receptor in guinea pig ileum	ic50	0.0004	uM
Montelukast	102663: In vitro inhibition of [3H]LTD4 binding to LTD4 receptor of guinea pig lung membrane with human serum albumin (HSA).	ic50	0.0004	uM
2-[1-(carboxymethyl)-7-[2-[4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl]ethynyl]-2-methylindol-3-yl]acetic acid	1236046: Antagonist activity at human CysLT1 expressed in CHOK1 cells assessed as inhibition of LTD4-induced calcium mobilization preincubated for 30 mins prior to LTD4 addition measured after 1 hr by Fura 2-AM dye-based fluorescence assay	ic50	0.0005	uM
4-heptoxy-N-[4-oxo-2-(2H-tetrazol-5-yl)chromen-8-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0005	uM
4-[(E)-hept-2-enoxy]-N-[3-(2H-tetrazol-5-yl)-2,3-dihydro-1,4-benzodioxin-5-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0005	uM
N-(2-bromophenyl)sulfonyl-4-[[5-[(2-cyclopentylacetyl)amino]-1-methylindol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0005	uM
4-[3-[(6,7-difluoroquinolin-2-yl)methoxy]anilino]-2,2-diethyl-4-oxobutanoic acid	102803: In vitro for antagonistic activity against LTD4 receptor in guinea pig ileum	ic50	0.0005	uM
2-[1-[[(1R)-3-[2-(2-hydroxypropan-2-yl)phenyl]-1-[3-[(E)-2-(8-methyl-5,6,7,8-tetrahydroquinolin-2-yl)ethenyl]phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0005	uM
2-[1-[[(1R)-1-[3-[(E)-2-(6-butyl-5-methyl-2-pyridinyl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102663: In vitro inhibition of [3H]LTD4 binding to LTD4 receptor of guinea pig lung membrane with human serum albumin (HSA).	ic50	0.0005	uM
2-[1-[[(1R)-3-[2-(2-hydroxypropan-2-yl)phenyl]-1-[3-[(E)-2-(5-methyl-6-propyl-2-pyridinyl)ethenyl]phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0005	uM
4-[8-[(E)-2-[4-(4-phenylbutoxy)phenyl]ethenyl]-2-(2H-tetrazol-5-yl)-2,3-dihydro-1,4-benzoxazin-4-yl]butanoic acid	1194279: Antagonist activity at human CysLT1 receptor expressed in CHO cells assessed as inhibition of LTD4-inudced intracellular calcium influx preincubated for 30 mins before LTD4 addition by Fura2-AM assay	ic50	0.0006	uM
4-[1-(carboxymethyl)-7-[(E)-2-[4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl]ethenyl]indol-3-yl]butanoic acid	1236046: Antagonist activity at human CysLT1 expressed in CHOK1 cells assessed as inhibition of LTD4-induced calcium mobilization preincubated for 30 mins prior to LTD4 addition measured after 1 hr by Fura 2-AM dye-based fluorescence assay	ic50	0.0006	uM
2-[1-[[(1R)-3-[2-(2-hydroxypropan-2-yl)phenyl]-1-[3-[(E)-2-(6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-2-yl)ethenyl]phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0006	uM
4-[1-(carboxymethyl)-7-[(E)-2-[4-[4-(3-chloro-2-methylphenyl)butoxy]phenyl]ethenyl]-2-methylindol-3-yl]butanoic acid	1236046: Antagonist activity at human CysLT1 expressed in CHOK1 cells assessed as inhibition of LTD4-induced calcium mobilization preincubated for 30 mins prior to LTD4 addition measured after 1 hr by Fura 2-AM dye-based fluorescence assay	ic50	0.0006	uM
4-oct-2-ynoxy-N-[3-(2H-tetrazol-5-yl)-2,3-dihydro-1,4-benzodioxin-5-yl]benzamide	78302: Inhibition of LTC4 induced smooth muscle contraction of guinea pig ileum	ic50	0.0007	uM
N-(2-chlorophenyl)sulfonyl-4-[[5-(cyclopentylcarbamoylamino)-1-methylindol-3-yl]methyl]-3-methoxybenzamide	55080: Inhibition constant for displacement of [3H]LTD4 on guinea pig lung parenchymal membranes.	ki	0.0007	uM
2-[1-[[(1R)-1-[3-[(E)-2-(2,3-dihydrothieno[3,2-b]pyridin-5-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid	102664: In vitro inhibition of [3H]-LTD4 binding to LTD4 receptor of guinea pig lung membrane without human serum albumin (HSA).	ic50	0.0007	uM

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
zafirlukast	increases response to substance, increases activity, affects binding, decreases activity, decreases reaction (+4 more)	22
Leukotriene D4	increases activity, increases abundance, increases reaction, increases response to substance, increases expression (+2 more)	15
pranlukast	affects binding, decreases activity, affects abundance, decreases reaction, increases response to substance (+2 more)	10
montelukast	decreases activity, decreases reaction, increases activity, increases abundance, increases expression (+1 more)	10
Calcium	decreases reaction, increases abundance, affects abundance, decreases activity, decreases abundance (+3 more)	10
verlukast	increases abundance, affects binding, decreases activity, decreases reaction, increases activity	7
Leukotriene C4	affects binding, decreases reaction, increases activity, increases abundance	6
pobilukast	affects binding, decreases activity, decreases reaction, increases activity, increases abundance	5
BAY u9773	affects binding, decreases activity, increases activity, decreases reaction, increases abundance	5
Aspirin	decreases reaction, increases expression, affects response to substance	5
Leukotriene E4	increases abundance, decreases reaction, affects binding, increases activity	4
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
acetylsalicylic acid lysinate	increases expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
LY 171883	affects binding, increases activity, decreases reaction	1
alpha-pentyl-3-(2-quinolinylmethoxy)benzenemethanol	increases activity, decreases activity, affects binding, decreases reaction	1
ICI 198615	decreases activity	1
iralukast	affects binding, decreases reaction	1
CGP 57698	affects binding, decreases reaction	1
CP 265298	affects binding, decreases activity, decreases abundance	1
CP 288886	affects binding, decreases activity, decreases abundance	1
CP 199330	affects abundance, affects binding, decreases activity	1
CP 199331	decreases activity, affects abundance, affects binding	1
MEN91507	affects binding, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Asbestos	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1

ChEMBL screening assays

139 unique, capped per target: 80 binding, 58 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1016594	Binding	Displacement of [3H]LTD4 from LTD4 receptor	The role of receptor binding in drug discovery. — J Nat Prod
CHEMBL1219966	Functional	Antagonist activity at CysLT1 receptor in human dU937 cells assessed as inhibition of LTD4-induced increase of calcium level treated 30 mins before LTD4 challenge	Pharmacophore identification, synthesis, and biological evaluation of carboxylated chalcone derivatives as CysLT1 antagonists. — Bioorg Med Chem
CHEMBL4810224	ADMET	Inhibition of LTD4 (unknown origin) at 0.1 to 1 uM	Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_H418	CHO-K1/CysLT1/Galpha15	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer