HCRTR2
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Also known as OX2ROXR2ORXR2
Summary
HCRTR2 (hypocretin receptor 2, HGNC:4849) is a protein-coding gene on chromosome 6p12.1, encoding Orexin receptor type 2 (O43614). G-protein coupled receptor that binds neuropeptides orexin-A and orexin-B, two neuropeptides derived from a common precursor, prepro-orexin.
The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein binds the hypothalamic neuropeptides orexin A and orexin B. A related gene (HCRTR1) encodes a G-protein coupled receptor that selectively binds orexin A.
Source: NCBI Gene 3062 — RefSeq curated summary.
At a glance
- Clinical variants (ClinVar): 56 total
- Druggable target: yes — 12 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_001384272
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:4849 |
| Approved symbol | HCRTR2 |
| Name | hypocretin receptor 2 |
| Location | 6p12.1 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | OX2R, OXR2, ORXR2 |
| Ensembl gene | ENSG00000137252 |
| Ensembl biotype | protein_coding |
| OMIM | 602393 |
| Entrez | 3062 |
Gene structure
Transcript identifiers
Ensembl transcripts: 2 — 2 protein_coding
ENST00000370862, ENST00000615358
RefSeq mRNA: 2 — MANE Select: NM_001384272
NM_001384272, NM_001526
CCDS: CCDS4956
Canonical transcript exons
ENST00000370862 — 7 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001015709 | 55277380 | 55277600 |
| ENSE00001135187 | 55280323 | 55280444 |
| ENSE00001135204 | 55263707 | 55263822 |
| ENSE00001135212 | 55255136 | 55255379 |
| ENSE00001135221 | 55248639 | 55248817 |
| ENSE00001453778 | 55282225 | 55282617 |
| ENSE00001453783 | 55174515 | 55174810 |
Expression profiles
Bgee: expression breadth broad, 56 present calls, max score 82.24.
FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0695 / max 31.3243, expressed in 27 samples.
FANTOM5 promoters (1 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 68307 | 0.0695 | 27 |
Top tissues by expression
262 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 82.24 | silver quality |
| cortical plate | UBERON:0005343 | 79.91 | gold quality |
| buccal mucosa cell | CL:0002336 | 72.60 | gold quality |
| frontal pole | UBERON:0002795 | 71.11 | gold quality |
| paraflocculus | UBERON:0005351 | 70.94 | gold quality |
| middle frontal gyrus | UBERON:0002702 | 70.61 | gold quality |
| endometrium epithelium | UBERON:0004811 | 67.20 | gold quality |
| endothelial cell | CL:0000115 | 65.94 | gold quality |
| adrenal tissue | UBERON:0018303 | 64.17 | gold quality |
| Brodmann (1909) area 10 | UBERON:0013541 | 60.54 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 60.09 | gold quality |
| prefrontal cortex | UBERON:0000451 | 57.62 | gold quality |
| ileal mucosa | UBERON:0000331 | 55.63 | silver quality |
| pons | UBERON:0000988 | 55.44 | gold quality |
| pancreatic ductal cell | CL:0002079 | 54.70 | silver quality |
| tibialis anterior | UBERON:0001385 | 54.70 | silver quality |
| biceps brachii | UBERON:0001507 | 54.26 | gold quality |
| hypothalamus | UBERON:0001898 | 53.17 | gold quality |
| cerebellar vermis | UBERON:0004720 | 53.15 | gold quality |
| calcaneal tendon | UBERON:0003701 | 53.09 | gold quality |
| metanephric glomerulus | UBERON:0004736 | 52.57 | gold quality |
| tibia | UBERON:0000979 | 51.63 | gold quality |
| deltoid | UBERON:0001476 | 51.43 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 51.40 | gold quality |
| Brodmann (1909) area 46 | UBERON:0006483 | 51.27 | gold quality |
| quadriceps femoris | UBERON:0001377 | 51.11 | gold quality |
| frontal cortex | UBERON:0001870 | 51.10 | gold quality |
| neocortex | UBERON:0001950 | 50.42 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 50.35 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 50.28 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 0.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 2.94 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): CREB1, GATA2, POU2F1
Literature-anchored findings (GeneRIF, showing 40)
- both OX1R and OX2R are expressed in the testis, epididymis, penis, and seminal vesicle (PMID:15070969)
- The data suggest that the HCRTR2 gene or a linked locus significantly modulates the risk for cluster headache. (PMID:15477554)
- All adrenal cortex adenomas expressed OX1-R and OX2-R mRNAs, and real-time PCR showed that the expression of both receptors was up-regulated in adenomas (PMID:15797953)
- Our results do not support a role of the HCRTR2 G1246A polymorphism in drug responses in CH. (PMID:17376114)
- polymorphism of the HCRTR2 gene may modulate the genetic risk for cluster headache (PMID:17563843)
- the HCRTR2 gene is not a genetic risk factor in migraine. (PMID:17645762)
- This study does not support a major contribution of the HCRTR2 G1246A polymorphism to the pathogenesis of migraine in contrast to its effects in cluster headache. (PMID:17883525)
- Three new polymorphisms of the HCRTR2 gene are significantly associated with cluster headache. (PMID:18399985)
- This study describes the intracellular signalling pathways involved in OX2R-mediated ERK(1/2) and p38 MAPK activation. (PMID:18599270)
- Both sporadic narcoleptic dogs and human narcolepsy-cataplexy subjects showed a significant decrease in hcrtR1 expression, while declines in hcrtR2 expression were not significant in these cases. (PMID:18714784)
- Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX(2) receptor. (PMID:19751316)
- Data demonstrated that hOX2R expression is regulated by a complex involving a proximal PKA/PKC-regulated promoter and a distal promoter regulating tissue-specific expression of alternative transcripts which in turn regulate receptor levels. (PMID:20156195)
- both OXA and OXR2 may be involved in the pathogenesis and/or maintenance of BPH. (PMID:21186399)
- analysis of orexin receptor 1 and 2 -arrestin-ubiquitin complexes (PMID:21378163)
- Results show that the N-terminal regions of orexin receptor are most important, and the exchange of the area from the C-terminal part of the transmembrane helix 2 to the transmembrane helix 4 is enough to lead to a change of the receptor’s ligand profile. (PMID:21510948)
- The Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls, were analyzed. (PMID:21666548)
- Intramolecular fluorescence resonance energy transfer (FRET) sensors of the orexin OX1 and OX2 receptors identify slow kinetics of agonist activation. (PMID:22389503)
- [review] Native orexin peptides consist of receptor agonists, orexin-A (33 amino acids) and orexin-B (28 amino acids) (aka hypocretin-1 and hypocretin-2). (PMID:23034387)
- Expression of the OX2R protein was detected in normal endometrial epithelia, whereas it was frequently lacking in endometrial endometrioid carcinoma. (PMID:23482607)
- DQ B1 but not HLA-DR typing, TNF-alpha levers, HCRTR1 and HCRTR2 were higher in narcolepsy-cataplexy/schizophrenia patients. (PMID:24268496)
- Both orexin receptor subtypes, OX1R and OX2R, and CB1 cannabinoid receptors are capable of forming constitutive homo- and heteromeric complexes. (PMID:24530395)
- Orexinergic innervation and expression of genes encoding OX2R receptor are upregulated in transgenic mice at dusk. (PMID:24599460)
- The genotypic and allelic frequencies of the rs2653349 polymorphism were different between Alzheimer’s disease patients and controls. The carriage of the G allele was associated with an increased AD risk. (PMID:24969517)
- Decrease in Ox expression with normal human maturation and aging. This may contribute to changes in sleep regulation during development and with aging. (PMID:25212464)
- our meta-analysis provides genetic evidence for a role of HCRTR2 in cluster headache (PMID:25398231)
- using lipid-mediated crystallization and protein engineering with a novel fusion chimaera, the structure of the human OX2R bound to suvorexant at 2.5 A resolution is solved (PMID:25533960)
- Antibodies from vaccine-associated narcolepsy sera cross-reacted with both influenza nucleoprotein and hypocretin receptor 2. (PMID:26136476)
- the nonsynonymous rs2653349 single nucleotide polymorphism (SNP) (located on the gene that encodes orexin [hypocretin] receptor 2) was selected as the most notable SNP associated with Fagerstrom Test for Nicotine Dependence. (PMID:26289589)
- Several single nucleotide polymorphisms (SNPs) in HCRTR2 were nominally associated with Antipsychotic-induced weight gain (AIWG) in patients of European ancestry treated with either clozapine or olanzapine. None of the SNPs in HCRTR1 were associated with AIWG. (PMID:26447462)
- Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation is highly unlikely to be caused by mutations in the exons of the HCRTR2 gene. (PMID:26555080)
- Heart failure patients with minor allele for rs7767652, upstream of hypocretin (orexin) receptor-2 (HCRTR2), were less likely to have improved left ventricular function and a lower prevalence of ejection fraction >35% (PMID:26653627)
- The study determined structures of OX1R bound to the OX1R-selective antagonist SB-674042 and the dual antagonist suvorexant at 2.8-A and 2.75-A resolution and explored mechanisms of antagonist the subtype selectivity between OX1R and OX2R. (PMID:26950369)
- G-protein-dependency of OX2 receptor signalling (PMID:27237973)
- This study showed that Lack of Association between Genetic Polymorphism of ox2r gene with Late Onset Depression and Alzheimer’s Disease in a Sample of a Brazilian Population (PMID:27335043)
- After sequencing all orexin receptor exons, one variation (rs2271933) in the OX1R gene and one variation (rs2653349) in the OX2R gene were found. However, no significant differences were found in either genotypic or allelic frequency distributions between the two study groups (PMID:27988352)
- The present study demonstrated that aa residues in the C-terminus serve an important role in the expression and signal transduction of OX2R. In addition, the aa residues in different locations possess evidentially different roles. (PMID:28487995)
- Like OX1R, OX2R has an N-terminal helix important for binding the orexin peptide. (PMID:29225076)
- Association between HCRTR2, ADH4,CLOCK gene polymorphisms and cluster headache was not significant in the present study. (PMID:29318394)
- The rs2653349 (G1246A) polymorphism of the HCRTR2 gene reduces the chance of developing cluster headache. (PMID:29959630)
- SNPs Leu72Met of the GHRL gene (rs696217), Ile408Val of the HCRTR1 gene (rs2271933) and Val308Ile of the HCRTR2 gene (rs2653349) were genotyped. None of the SNPs showed significant main or G x E effects in post-traumatic stress disorder patients. (PMID:30326460)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | hcrtr2 | ENSDARG00000023722 |
| mus_musculus | Hcrtr2 | ENSMUSG00000032360 |
| rattus_norvegicus | Hcrtr2 | ENSRNOG00000011251 |
Paralogs (16): NPFFR2 (ENSG00000056291), GNRHR (ENSG00000109163), CCKBR (ENSG00000110148), HCRTR1 (ENSG00000121764), AVPR2 (ENSG00000126895), GALR3 (ENSG00000128310), NPFFR1 (ENSG00000148734), CCKAR (ENSG00000163394), AVPR1A (ENSG00000166148), GALR1 (ENSG00000166573), GPR22 (ENSG00000172209), GPR150 (ENSG00000178015), OXTR (ENSG00000180914), FFAR4 (ENSG00000186188), QRFPR (ENSG00000186867), AVPR1B (ENSG00000198049)
Protein
Protein identifiers
Orexin receptor type 2 — O43614 (reviewed: O43614)
Alternative names: Hypocretin receptor type 2
All UniProt accessions (2): O43614, S4X0W3
UniProt curated annotations — full annotation on UniProt →
Function. G-protein coupled receptor that binds neuropeptides orexin-A and orexin-B, two neuropeptides derived from a common precursor, prepro-orexin. Upon neuropeptide ligand binding, HCRTR2 can couple with both G(q)/11 and G(i)/o heterotrimeric G-proteins thereby initiating distinct downstream signaling cascades. Involved in regulating the sleep-wake cycle. Contributes to central regulation of glucose homeostasis.
Subcellular location. Cell membrane.
Domain organisation. The N-terminal region is required for orexin signaling.
Similarity. Belongs to the G-protein coupled receptor 1 family.
RefSeq proteins (2): NP_001371201, NP_001517 (=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000204 | Orexin_rcpt | Family |
| IPR000276 | GPCR_Rhodpsn | Family |
| IPR004060 | Orexin_rcpt_2 | Family |
| IPR017452 | GPCR_Rhodpsn_7TM | Domain |
Pfam: PF00001, PF03827
UniProt features (56 total): helix 13, topological domain 8, transmembrane region 7, mutagenesis site 7, strand 5, sequence variant 4, glycosylation site 3, region of interest 2, turn 2, chain 1, compositionally biased region 1, binding site 1, site 1, disulfide bond 1
Structure
Experimental structures (PDB)
12 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 5WQC | X-RAY DIFFRACTION | 1.96 |
| 5WS3 | X-RAY DIFFRACTION | 2.3 |
| 4S0V | X-RAY DIFFRACTION | 2.5 |
| 6TPN | X-RAY DIFFRACTION | 2.61 |
| 6TPJ | X-RAY DIFFRACTION | 2.74 |
| 6TPG | X-RAY DIFFRACTION | 2.74 |
| 7XRR | X-RAY DIFFRACTION | 2.89 |
| 7L1V | ELECTRON MICROSCOPY | 3 |
| 7SQO | ELECTRON MICROSCOPY | 3.17 |
| 7L1U | ELECTRON MICROSCOPY | 3.2 |
| 21CI | X-RAY DIFFRACTION | 3.29 |
| 7SR8 | ELECTRON MICROSCOPY | 3.3 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-O43614-F1 | 79.33 | 0.52 |
Antibody-complex structures (SAbDab): 4 — 7L1U, 7L1V, 7SQO, 7SR8
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1): 44 (important for responses to orexin)
Ligand- & substrate-binding residues (1): 324
Disulfide bonds (1): 127–210
Glycosylation sites (3): 14, 22, 202
Mutagenesis-validated functional residues (7):
| Position | Phenotype |
|---|---|
| 33–49 | abolishes response to orexin-a. |
| 44 | abolishes response to orexin-a. |
| 111 | reduces response to tak-925. abolishes response to orexin-b. |
| 111 | reduces response to tak-925. |
| 134 | abolishes response to tak-925. abolishes response to orexin-b. |
| 135 | reduces response to tak-925. |
| 324 | strongly impairs response to orexin-a. does not affect response to tak-925. abolishes response to orexin-b. |
Function
Pathways and Gene Ontology
Reactome pathways
2 pathways
| ID | Pathway |
|---|---|
| R-HSA-389397 | Orexin and neuropeptides FF and QRFP bind to their respective receptors |
| R-HSA-416476 | G alpha (q) signalling events |
MSigDB gene sets: 122 (showing top):
GOBP_CIRCADIAN_RHYTHM, GOBP_BEHAVIOR, MORF_RAD51L3, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_BEHAVIOR, chr6p12, MODULE_289, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, MORF_CTSB, MORF_IL4, MORF_PRKCA, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_RESPONSE_TO_HORMONE
GO Biological Process (12): phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), neuropeptide signaling pathway (GO:0007218), chemical synaptic transmission (GO:0007268), feeding behavior (GO:0007631), regulation of circadian sleep/wake cycle, wakefulness (GO:0010840), circadian sleep/wake cycle process (GO:0022410), cellular response to hormone stimulus (GO:0032870), locomotion (GO:0040011), glucose homeostasis (GO:0042593), regulation of cytosolic calcium ion concentration (GO:0051480), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)
GO Molecular Function (5): neuropeptide receptor activity (GO:0008188), orexin receptor activity (GO:0016499), peptide hormone binding (GO:0017046), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)
GO Cellular Component (4): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), synapse (GO:0045202), membrane (GO:0016020)
Reactome top-level categories
Rollup of top-2 pathways:
| Category | Pathways |
|---|---|
| Peptide ligand-binding receptors | 1 |
| GPCR downstream signalling | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| G protein-coupled receptor signaling pathway | 3 |
| G protein-coupled peptide receptor activity | 2 |
| cellular anatomical structure | 2 |
| phospholipase C activator activity | 1 |
| anterograde trans-synaptic signaling | 1 |
| behavior | 1 |
| circadian sleep/wake cycle, wakefulness | 1 |
| regulation of circadian sleep/wake cycle | 1 |
| circadian sleep/wake cycle | 1 |
| circadian behavior | 1 |
| response to hormone | 1 |
| cellular response to chemical stimulus | 1 |
| cellular response to endogenous stimulus | 1 |
| biological_process | 1 |
| carbohydrate homeostasis | 1 |
| intracellular calcium ion homeostasis | 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 |
| signal transduction | 1 |
| neuropeptide signaling pathway | 1 |
| neuropeptide binding | 1 |
| hormone binding | 1 |
| transmembrane signaling receptor activity | 1 |
| binding | 1 |
| nuclear lumen | 1 |
| membrane | 1 |
| cell periphery | 1 |
| cell junction | 1 |
Protein interactions and networks
STRING
640 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| HCRTR2 | HCRT | O43612 | 996 |
| HCRTR2 | POMC | P01189 | 703 |
| HCRTR2 | OXR1 | Q8N573 | 693 |
| HCRTR2 | OR13H1 | Q8NG92 | 480 |
| HCRTR2 | PMCH | P20382 | 474 |
| HCRTR2 | TRIB2 | Q92519 | 438 |
| HCRTR2 | GHSR | Q92847 | 435 |
| HCRTR2 | HLA-DQB1 | P01917 | 392 |
| HCRTR2 | FEV | Q99581 | 381 |
| HCRTR2 | PDYN | P01213 | 380 |
| HCRTR2 | ATXN3L | Q9H3M9 | 375 |
| HCRTR2 | NPY | P01303 | 374 |
| HCRTR2 | ATXN3 | P54252 | 366 |
| HCRTR2 | AGRP | O00253 | 344 |
| HCRTR2 | NPS | P0C0P6 | 322 |
IntAct
12 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| PPIA | HCRTR2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| HCRTR2 | RAMP1 | psi-mi:“MI:0915”(physical association) | 0.400 |
| RAMP1 | HCRTR2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| HCRTR2 | RAMP3 | psi-mi:“MI:0915”(physical association) | 0.400 |
| HCRTR2 | RAMP2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| RAMP3 | HCRTR2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| HCRTR2 | FADS1 | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (35): SLC7A3 (Affinity Capture-MS), TSPAN15 (Affinity Capture-MS), XPO7 (Affinity Capture-MS), SELT (Affinity Capture-MS), MRS2 (Affinity Capture-MS), MTX1 (Affinity Capture-MS), LMBRD2 (Affinity Capture-MS), ULBP3 (Affinity Capture-MS), ATP2B4 (Affinity Capture-MS), NLRX1 (Affinity Capture-MS), FASTKD1 (Affinity Capture-MS), SLC39A6 (Affinity Capture-MS), FAM162A (Affinity Capture-MS), NT5C1A (Affinity Capture-MS), INTS1 (Affinity Capture-MS)
ESM2 similar proteins: A0A2L0VBG2, A1ZAX0, B2ZHY2, O43194, O43614, O46635, O46639, O54798, O62809, O93603, O97967, P08909, P14842, P18599, P20789, P21761, P28223, P28335, P30975, P32247, P32940, P34968, P34981, P35363, P35371, P41984, P47751, P50128, P50129, P56490, P56719, P58308, Q01717, Q28596, Q4V622, Q5IS53, Q5IS66, Q5IS98, Q5R4Q6, Q5U431
Diamond homologs: A5A4K9, A5A4L1, C3ZQF9, F1MV99, G4WMX4, O02835, O02836, O08725, O42179, O43614, O54799, O62729, O62809, O70342, O77408, P0DQD5, P11617, P20288, P22270, P24053, P24628, P25929, P25931, P28336, P29274, P30731, P30938, P30975, P32251, P35346, P35371, P41143, P47211, P47751, P49146, P49219, P49285, P49288, P49683, P50391
SIGNOR signaling
9 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| HCRTR2 | “up-regulates activity” | GNAI1 | binding |
| HCRTR2 | “up-regulates activity” | GNAI3 | binding |
| HCRTR2 | “up-regulates activity” | GNAO1 | binding |
| HCRTR2 | “up-regulates activity” | GNAZ | binding |
| HCRTR2 | “up-regulates activity” | GNAQ | binding |
| HCRTR2 | “up-regulates activity” | GNA14 | binding |
| HCRTR2 | “up-regulates activity” | GNA13 | binding |
| “Orexin A” | “up-regulates activity” | HCRTR2 | “chemical activation” |
| HCRT | up-regulates | HCRTR2 | binding |
Disease & clinical
Clinical variants and AI predictions
ClinVar
56 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 44 |
| Likely benign | 5 |
| Benign | 4 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
0 predictions. Top by Δscore:
AlphaMissense
2901 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 6:55248700:T:A | N95K | 1.000 |
| 6:55248700:T:G | N95K | 1.000 |
| 6:55255188:G:C | R152P | 1.000 |
| 6:55280421:C:A | P361Q | 1.000 |
| 6:55174798:G:A | G71R | 0.999 |
| 6:55174798:G:C | G71R | 0.999 |
| 6:55174799:G:A | G71E | 0.999 |
| 6:55174799:G:T | G71V | 0.999 |
| 6:55174803:C:A | N72K | 0.999 |
| 6:55174803:C:G | N72K | 0.999 |
| 6:55248670:G:A | M85I | 0.999 |
| 6:55248670:G:C | M85I | 0.999 |
| 6:55248670:G:T | M85I | 0.999 |
| 6:55248685:C:A | N90K | 0.999 |
| 6:55248685:C:G | N90K | 0.999 |
| 6:55248693:T:A | I93K | 0.999 |
| 6:55248702:T:C | L96P | 0.999 |
| 6:55248795:G:A | C127Y | 0.999 |
| 6:55248796:C:G | C127W | 0.999 |
| 6:55255169:A:C | S146R | 0.999 |
| 6:55255171:C:A | S146R | 0.999 |
| 6:55255171:C:G | S146R | 0.999 |
| 6:55255200:T:A | I156N | 0.999 |
| 6:55255262:T:A | W177R | 0.999 |
| 6:55255262:T:C | W177R | 0.999 |
| 6:55255361:T:A | C210S | 0.999 |
| 6:55255362:G:A | C210Y | 0.999 |
| 6:55255362:G:C | C210S | 0.999 |
| 6:55263797:T:A | I246K | 0.999 |
| 6:55277554:T:C | F313L | 0.999 |
dbSNP variants (sampled 300 via entrez): RS1000012855 (6:55116420 A>T), RS1000018173 (6:55202796 G>A), RS1000018755 (6:55239742 G>T), RS1000025469 (6:55129907 T>A), RS1000042194 (6:55118491 G>A), RS1000051888 (6:55267258 A>G), RS1000056124 (6:55186154 T>C), RS1000058335 (6:55130234 T>A), RS1000072831 (6:55171914 G>A), RS1000078810 (6:55204590 GCT>G), RS1000126597 (6:55172192 C>T), RS1000131163 (6:55207788 T>A,C), RS1000132297 (6:55280186 A>G,T), RS1000148220 (6:55122697 G>A,T), RS1000165290 (6:55143362 T>C)
Disease associations
OMIM: gene MIM:602393 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
0 associations (top):
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (2): CHEMBL3307226 (PROTEIN FAMILY), CHEMBL4792 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,810 (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 |
|---|---|---|---|
| CHEMBL1083659 | SUVOREXANT | 4 | 852 |
| CHEMBL3545367 | LEMBOREXANT | 4 | 271 |
| CHEMBL4297590 | DARIDOREXANT | 4 | 102 |
| CHEMBL3597971 | SELTOREXANT | 3 | 120 |
| CHEMBL455136 | ALMOREXANT | 3 | 218 |
| CHEMBL1272307 | SB-649868 | 2 | 21 |
| CHEMBL2107822 | FILOREXANT | 2 | 50 |
| CHEMBL3892369 | NIVASOREXANT | 2 | 18 |
| CHEMBL4650341 | DANAVOREXTON | 2 | 131 |
| CHEMBL3338866 | MK-1064 | 1 | 9 |
| CHEMBL3597952 | ACT-462206 | 1 | 11 |
| CHEMBL3958101 | CVN-766 | 1 | 7 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: gpcr — Orexin receptors
Most potent curated ligand interactions (45 total), top 25:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| orexin-A | Full agonist | 10.0 | pEC50 |
| orexin-B | Full agonist | 10.0 | pEC50 |
| [Ala11, D-Leu15]orexin-B | Full agonist | 9.9 | pEC50 |
| [3H]-almorexant | Antagonist | 9.8 | pKd |
| TCS 1102 | Antagonist | 9.7 | pKB |
| SB-649868 | Antagonist | 9.6 | pKB |
| suvorexant | Antagonist | 9.4 | pKi |
| [3H]Cp-1 | Antagonist | 9.4 | pKd |
| lemborexant | Antagonist | 9.3 | pKi |
| daridorexant | Antagonist | 9.2 | pKB |
| EMPA | Antagonist | 9.2 | pKi |
| Cp-1 | Antagonist | 9.15 | pKi |
| filorexant | Antagonist | 9.1 | pKi |
| MK-1064 | Antagonist | 9.1 | pKi |
| [3H]-TCS 1102 | Antagonist | 9.0 | pKd |
| MK-3697 | Antagonist | 9.0 | pKi |
| [3H]EMPA | Antagonist | 9.0 | pKd |
| vornorexant | Antagonist | 8.9 | pIC50 |
| almorexant | Antagonist | 8.9 | pKB |
| seltorexant | Antagonist | 8.8 | pKB |
| oveporexton | Agonist | 8.6 | pEC50 |
| ACT-462206 | Antagonist | 8.6 | pKB |
| T-516 | Full agonist | 8.37 | pEC50 |
| LSN2424100 | Antagonist | 8.35 | pKi |
| HTL6641 | Antagonist | 8.3 | pKi |
Binding affinities (BindingDB)
5606 measured of 5968 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| (2R,3S)-N-ethyl-2-(((cis-4-(3- fluorophenyl)cyclohexyl)oxy)- methyl)-3- ((methylsulfonyl)amino)piperidine- 1-carboxamide | EC50 | 0.053 nM | US-10287305: Substituted piperidine compound and use thereof |
| (2R,3S)-N-ethyl-3- ((methylsulfonyl)amino)-2-(((cis-4- phenylcyclohexyl)oxy)methyl)- piperidine-1-carboxamide | EC50 | 0.11 nM | US-10287305: Substituted piperidine compound and use thereof |
| cis-N-ethyl-2-(((cis-4-(2- fluorophenyl)cyclohexyl)oxy)-methyl)- 3-((methylsulfonyl)amino)piperidine-1- carboxamide | EC50 | 0.12 nM | US-10287305: Substituted piperidine compound and use thereof |
| cis-2-(((cis-4-(2,3- difluorophenyl)cyclohexyl)oxy)- methyl)-N-ethyl-3- ((methylsulfonyl)amino)piperidine- 1-carboxamide | EC50 | 0.22 nM | US-10287305: Substituted piperidine compound and use thereof |
| cis-N-(cyanomethyl)-3- ((methylsulfonyl)amino)-2-(((cis-4- phenylcyclohexyl)oxy)methyl)- piperidine-1-carboxamide | EC50 | 0.31 nM | US-10287305: Substituted piperidine compound and use thereof |
| [(2R,5R)-2-[(5-fluoro-2-pyridinyl)oxymethyl]-5-methylthiomorpholin-4-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone | KI | 0.38 nM | US-9029364: 2,5-disubstituted thiomorpholine orexin receptor antagonists |
| [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2S)-2-[5-(3-fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]pyrrolidin-1-yl]methanone | IC50 | 0.4 nM | US-9493446: Orexin receptor antagonists which are [ortho bi-(hetero-)aryl]-[2-(meta bi-(hetero-)aryl)-pyrrolidin-1-yl]-methanone derivatives |
| N-((2R,3S)-1-(cyclopropylcarbonyl)- 2-(((cis-4-(2,6- difluorophenyl)cyclohexyl)oxy)- methyl)piperidin-3- yl)methanesulfonamide | EC50 | 0.44 nM | US-10287305: Substituted piperidine compound and use thereof |
| cis-3-((cyclopropylsulfonyl)amino)- N-ethyl-2-(((cis-4- phenylcyclohexyl)oxy)methyl)- piperidine-1-carboxamide | EC50 | 0.44 nM | US-10287305: Substituted piperidine compound and use thereof |
| [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2S)-2-[5-(2-ethoxy-3-pyridinyl)-1,2,4-oxadiazol-3-yl]pyrrolidin-1-yl]methanone | IC50 | 0.5 nM | US-9493446: Orexin receptor antagonists which are [ortho bi-(hetero-)aryl]-[2-(meta bi-(hetero-)aryl)-pyrrolidin-1-yl]-methanone derivatives |
| [(2S)-2-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]-[5-(3-methoxyphenyl)-2-methyl-1,3-thiazol-4-yl]methanone | IC50 | 0.5 nM | US-9732075: Benzimidazole-proline derivatives |
| [(2S)-2-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone | IC50 | 0.5 nM | US-9732075: Benzimidazole-proline derivatives |
| [(2R,5R)-5-(8-fluoroquinolin-4-yl)oxy-2-methylpiperidin-1-yl]-[2-(triazol-2-yl)phenyl]methanone | KI | 0.55 nM | US-8710076: 2,5-disubstituted piperidine orexin receptor antagonists |
| (2R,3S)-N-ethyl-3- ((methylsulfonyl)amino)-2-(((cis-4- (2-(trifluoromethyl)phenyl)- cyclohexyl)oxy)methyl)piperidine-1- carboxamide | EC50 | 0.55 nM | US-10287305: Substituted piperidine compound and use thereof |
| [(2R,5R)-5-(isoquinolin-1-ylamino)-2-methylpiperidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone | KI | 0.56 nM | US-8710076: 2,5-disubstituted piperidine orexin receptor antagonists |
| [(2S)-2-[5-(3-fluoro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone | IC50 | 0.6 nM | US-9403813: Azetidine amide derivatives as orexin receptor antagonists |
| [4,5-dimethyl-2-(triazol-2-yl)phenyl]-[(2S)-2-[5-(2-ethoxy-3-pyridinyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone | IC50 | 0.6 nM | US-9403813: Azetidine amide derivatives as orexin receptor antagonists |
| [(2S)-2-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]-[2-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazol-4-yl]methanone | IC50 | 0.6 nM | US-9732075: Benzimidazole-proline derivatives |
| [(2S)-2-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]-[2-methyl-5-(3-methylphenyl)-1,3-thiazol-4-yl]methanone | IC50 | 0.6 nM | US-9732075: Benzimidazole-proline derivatives |
| [(2S)-2-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]-[4,5-dimethyl-2-(triazol-2-yl)phenyl]methanone | IC50 | 0.6 nM | US-9732075: Benzimidazole-proline derivatives |
| (4,5-Dimethyl-2-[1,2,3]triazol-2-yl-phenyl)-[(S)-2-(6-methoxy-1H-benzoimidazol-2-yl)-4-methylene-pyrrolidin-1-yl]-methanone | IC50 | 0.6 nM | US-9732075: Benzimidazole-proline derivatives |
| cis-N-ethyl-3- ((methylsulfonyl)amino)-2-(((cis-4- (2-(trifluoromethyl)phenyl)- cyclohexyl)oxy)methyl)piperidine-1- carboxamide | EC50 | 0.61 nM | US-10287305: Substituted piperidine compound and use thereof |
| N-((2R,3S)-1-(cyclopropylcarbonyl)- 2-(((cis-4- phenylcyclohexyl)oxy)methyl)- piperidin-3-yl)methanesulfonamide | EC50 | 0.66 nM | US-10287305: Substituted piperidine compound and use thereof |
| N-[(5,6-dimethoxy-3-methyl-2-pyridinyl)methyl]-6-(5-methyl-3-pyridinyl)-3-thiophen-2-yl-[1,2]oxazolo[5,4-b]pyridine-4-carboxamide | KI | 0.7 nM | US-9242995: Isoxazolopyridine orexin receptor antagonists |
| [(2S)-2-(4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]-[2-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-thiazol-4-yl]methanone | IC50 | 0.7 nM | US-9732075: Benzimidazole-proline derivatives |
| [5-(3-methoxyphenyl)-2-methyl-1,3-thiazol-4-yl]-[(2S)-2-(4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]methanone | IC50 | 0.7 nM | US-9732075: Benzimidazole-proline derivatives |
| [5-(3-bromophenyl)-2-methyl-1,3-thiazol-4-yl]-[(2S)-2-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]methanone | IC50 | 0.7 nM | US-9732075: Benzimidazole-proline derivatives |
| [(2S)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone | IC50 | 0.7 nM | US-9403813: Azetidine amide derivatives as orexin receptor antagonists |
| N-[(5,6-dimethoxy-2-pyridinyl)methyl]-2-(5-methyl-3-pyridinyl)-5-phenylpyridine-4-carboxamide | KI | 0.72 nM | US-8592457: Isonicotinamide orexin receptor antagonists |
| N-((2R,3S)-1-(cyclopropylcarbonyl)- 2-(((cis-4-(2,3,6- trifluorophenyl)cyclohexyl)oxy)- methyl)piperidin-3- yl)methanesulfonamide | EC50 | 0.72 nM | US-10287305: Substituted piperidine compound and use thereof |
| [5-(3-bromophenyl)-2-methyl-1,3-thiazol-4-yl]-[(2S)-2-(4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]methanone | IC50 | 0.8 nM | US-9732075: Benzimidazole-proline derivatives |
| [5-(3-bromo-4-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]-[(2S)-2-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]methanone | IC50 | 0.8 nM | US-9732075: Benzimidazole-proline derivatives |
| [(2S)-2-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]-[5-(3,4-dichlorophenyl)-2-methyl-1,3-thiazol-4-yl]methanone | IC50 | 0.8 nM | US-9732075: Benzimidazole-proline derivatives |
| N-((2R,3S)-1-(cyclopropylcarbonyl)- 2-(((cis-4-(3- fluorophenyl)cyclohexyl)oxy)- methyl)piperidin-3- yl)methanesulfonamide | EC50 | 0.84 nM | US-10287305: Substituted piperidine compound and use thereof |
| N-((2R,3S)-1-(cyclopropylcarbonyl)- 2-(((cis-4-(3,5- difluorophenyl)cyclohexyl)oxy)- methyl)piperidin-3- yl)methanesulfonamide | EC50 | 0.88 nM | US-10287305: Substituted piperidine compound and use thereof |
| [(2R,5R)-2-[(5-fluoro-2-pyridinyl)oxymethyl]-5-methylthiomorpholin-4-yl]-[2-(triazol-2-yl)phenyl]methanone | KI | 0.9 nM | US-9029364: 2,5-disubstituted thiomorpholine orexin receptor antagonists |
| [(2S)-2-(4-methyl-1H-benzimidazol-2-yl)-4-methylidenepyrrolidin-1-yl]-[2-methyl-5-(3-methylphenyl)-1,3-thiazol-4-yl]methanone | IC50 | 0.9 nM | US-9732075: Benzimidazole-proline derivatives |
| N-[(5,6-dimethoxy-2-pyridinyl)methyl]-5-(3-fluorophenyl)-2-(5-methyl-3-pyridinyl)pyridine-4-carboxamide | KI | 0.91 nM | US-8592457: Isonicotinamide orexin receptor antagonists |
| N-[(5,6-dimethoxy-2-pyridinyl)methyl]-2-(5-methyl-3-pyridinyl)-5-(1,3-thiazol-2-yl)pyridine-4-carboxamide | KI | 0.95 nM | US-8592457: Isonicotinamide orexin receptor antagonists |
| 6-(3-chloro-5-methylphenyl)-N-[(3,4-dimethoxyphenyl)methyl]-3-morpholin-4-ylpyridazine-4-carboxamide | KI | 0.96 nM | US-8703770: Pyridazine carboxamide orexin receptor antagonists |
| N-[(5-cyclopropyl-6-methoxy-2-pyridinyl)methyl]-2-(5-methyl-3-pyridinyl)-5-(1,3-thiazol-2-yl)pyridine-4-carboxamide | KI | 0.97 nM | US-8592457: Isonicotinamide orexin receptor antagonists |
| 1-(dibenzofuran-2-ylmethyl)-6-(3,5-dimethoxy-4-pyridinyl)piperidin-2-one | IC50 | 1 nM | US-9242970: Lactam derivatives useful as orexin receptor antagonists |
| (3S,5S)-1-(dibenzofuran-2-ylmethyl)-5-(2,6-dimethoxyphenyl)-3-fluoropyrrolidin-2-one | IC50 | 1 nM | US-9242970: Lactam derivatives useful as orexin receptor antagonists |
| [2-[[4-(4-fluorophenyl)pyrazol-1-yl]methyl]-1,3-oxazinan-3-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone | IC50 | 1 nM | US-9266870: Heteroaromatic methyl cyclic amine derivative |
| [2-[[3-(4-fluorophenyl)pyrazol-1-yl]methyl]-1,3-oxazinan-3-yl]-(5-methyl-2-pyrimidin-2-ylphenyl)methanone | IC50 | 1 nM | US-9266870: Heteroaromatic methyl cyclic amine derivative |
| [(2S)-2-[5-(2-ethoxy-3-pyridinyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[5-methoxy-4-methyl-2-(triazol-2-yl)phenyl]methanone | IC50 | 1 nM | US-9403813: Azetidine amide derivatives as orexin receptor antagonists |
| [4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]-[(2S)-2-[5-(2-ethoxy-3-pyridinyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone | IC50 | 1 nM | US-9403813: Azetidine amide derivatives as orexin receptor antagonists |
| [5-chloro-4-methyl-2-(triazol-2-yl)phenyl]-[(2S)-2-[5-(2-ethoxy-3-pyridinyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]methanone | IC50 | 1 nM | US-9403813: Azetidine amide derivatives as orexin receptor antagonists |
| [(2S)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4,5-dimethyl-2-(triazol-2-yl)phenyl]methanone | IC50 | 1 nM | US-9403813: Azetidine amide derivatives as orexin receptor antagonists |
| [(2S)-2-[5-(3-chloro-2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]azetidin-1-yl]-[4-chloro-5-methoxy-2-(triazol-2-yl)phenyl]methanone | IC50 | 1 nM | US-9403813: Azetidine amide derivatives as orexin receptor antagonists |
ChEMBL bioactivities
6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 11.00 | EC50 | 0.01 | nM | CHEMBL6133656 |
| 11.00 | EC50 | 0.01 | nM | CHEMBL6149831 |
| 11.00 | EC50 | 0.01 | nM | CHEMBL6164486 |
| 11.00 | EC50 | 0.01 | nM | CHEMBL6170458 |
| 11.00 | EC50 | 0.01 | nM | CHEMBL6150209 |
| 11.00 | EC50 | 0.01 | nM | CHEMBL6133718 |
| 10.40 | IC50 | 0.04 | nM | CHEMBL5196538 |
| 10.30 | IC50 | 0.05 | nM | CHEMBL5194793 |
| 10.28 | EC50 | 0.052 | nM | CHEMBL438587 |
| 10.28 | EC50 | 0.053 | nM | CHEMBL5917431 |
| 10.19 | EC50 | 0.065 | nM | CHEMBL413504 |
| 10.18 | EC50 | 0.066 | nM | CHEMBL441918 |
| 10.15 | Ki | 0.07 | nM | CHEMBL3099899 |
| 10.15 | IC50 | 0.07 | nM | CHEMBL5177846 |
| 10.09 | EC50 | 0.081 | nM | OREXIN B |
| 10.08 | EC50 | 0.084 | nM | CHEMBL438036 |
| 10.05 | Ki | 0.09 | nM | CHEMBL272715 |
| 10.05 | IC50 | 0.09 | nM | CHEMBL5195414 |
| 10.04 | EC50 | 0.091 | nM | CHEMBL436915 |
| 10.00 | Ki | 0.1 | nM | CHEMBL3741853 |
| 10.00 | Ki | 0.1 | nM | CHEMBL3770503 |
| 10.00 | Ki | 0.1 | nM | CHEMBL255763 |
| 10.00 | IC50 | 0.1 | nM | CHEMBL5190821 |
| 10.00 | IC50 | 0.1 | nM | CHEMBL5206338 |
| 10.00 | Ki | 0.1 | nM | CHEMBL5903207 |
| 10.00 | Ki | 0.1 | nM | CHEMBL5830018 |
| 10.00 | Ki | 0.1 | nM | CHEMBL6053220 |
| 10.00 | Ki | 0.1 | nM | CHEMBL6038743 |
| 10.00 | Ki | 0.1 | nM | CHEMBL6033221 |
| 9.96 | EC50 | 0.11 | nM | CHEMBL428123 |
| 9.96 | Ki | 0.11 | nM | CHEMBL3394829 |
| 9.96 | EC50 | 0.11 | nM | CHEMBL5089283 |
| 9.92 | EC50 | 0.12 | nM | CHEMBL410480 |
| 9.92 | EC50 | 0.12 | nM | CHEMBL427771 |
| 9.92 | EC50 | 0.12 | nM | CHEMBL6049058 |
| 9.89 | EC50 | 0.13 | nM | CHEMBL437464 |
| 9.89 | EC50 | 0.13 | nM | CHEMBL414312 |
| 9.89 | EC50 | 0.13 | nM | CHEMBL409301 |
| 9.82 | EC50 | 0.15 | nM | CHEMBL437149 |
| 9.82 | EC50 | 0.15 | nM | CHEMBL265746 |
| 9.82 | EC50 | 0.15 | nM | CHEMBL410947 |
| 9.80 | EC50 | 0.16 | nM | CHEMBL265423 |
| 9.80 | EC50 | 0.16 | nM | CHEMBL410899 |
| 9.80 | EC50 | 0.16 | nM | CHEMBL439541 |
| 9.78 | Ki | 0.166 | nM | CHEMBL2435400 |
| 9.77 | Ki | 0.17 | nM | CHEMBL1083358 |
| 9.74 | EC50 | 0.18 | nM | CHEMBL265404 |
| 9.74 | EC50 | 0.18 | nM | CHEMBL5079059 |
| 9.72 | EC50 | 0.19 | nM | CHEMBL410816 |
| 9.70 | Ki | 0.2 | nM | CHEMBL3235249 |
PubChem BioAssay actives
1722 with measured affinity, of 2956 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 |
|---|---|---|---|---|
| N-(13-methyl-11-oxo-7,10,18-trioxa-12,24-diazatetracyclo[17.2.2.12,6.012,16]tetracosa-2(24),3,5-trien-15-yl)methanesulfonamide | 1893730: Agonist activity at human OX2R expressed in CHO cells incubated for 2 hrs by IP-one detection reagent based fluorescence assay | ic50 | <0.0001 | uM |
| N-(3,5-difluoro-13-methyl-11-oxo-7,10,18-trioxa-12,24-diazatetracyclo[17.2.2.12,6.012,16]tetracosa-2(24),3,5-trien-15-yl)methanesulfonamide | 1893730: Agonist activity at human OX2R expressed in CHO cells incubated for 2 hrs by IP-one detection reagent based fluorescence assay | ic50 | 0.0001 | uM |
| 15-(dimethylsulfamoylamino)-13-methyl-11-oxo-7,10,18-trioxa-12-azatetracyclo[17.2.2.12,6.012,16]tetracosa-2(24),3,5-triene | 1893730: Agonist activity at human OX2R expressed in CHO cells incubated for 2 hrs by IP-one detection reagent based fluorescence assay | ic50 | 0.0001 | uM |
| N-(3,13-dimethyl-11-oxo-7,10,18-trioxa-12,24-diazatetracyclo[17.2.2.12,6.012,16]tetracosa-2,4,6(24)-trien-15-yl)methanesulfonamide | 1893730: Agonist activity at human OX2R expressed in CHO cells incubated for 2 hrs by IP-one detection reagent based fluorescence assay | ic50 | 0.0001 | uM |
| N-(14-methyl-12-oxo-7,11,19-trioxa-13,25-diazatetracyclo[18.2.2.12,6.013,17]pentacosa-2(25),3,5-trien-16-yl)methanesulfonamide | 1893730: Agonist activity at human OX2R expressed in CHO cells incubated for 2 hrs by IP-one detection reagent based fluorescence assay | ic50 | 0.0001 | uM |
| (8E,13R,15S,16R)-15-(dimethylsulfamoylamino)-13-methyl-11-oxo-10,18-dioxa-12-azatetracyclo[17.2.2.02,7.012,16]tricosa-2,4,6,8-tetraene | 1893730: Agonist activity at human OX2R expressed in CHO cells incubated for 2 hrs by IP-one detection reagent based fluorescence assay | ic50 | 0.0001 | uM |
| 5-(3,5-dichlorophenyl)-N-[(3,4-dimethoxyphenyl)methyl]-2-pyridin-3-ylpyridine-3-carboxamide | 1060408: Displacement of [3H]SB-674042 from human orexin-2 receptor after 60 mins by scintillation counting analysis | ki | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[(2S)-1-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-1-oxopropan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]acetyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2R)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2R)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2R)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[(2R)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0001 | uM |
| (2S)-1-[2-(1,6-dimethylbenzimidazol-2-yl)sulfanylacetyl]-N-(2-pyrrol-1-ylphenyl)pyrrolidine-2-carboxamide | 321311: Displacement of 3H-N-(2-(1H-pyrrol-1-yl)phenyl)-1-(2-(1-methyl-1H-benzo[d]imidazol-2-ylthio)acetyl)pyrrolidine-2-carboxamide from human OX2R expressed in CHO cells | ki | 0.0001 | uM |
| (2S)-1-[2-(1,5-dimethylbenzimidazol-2-yl)sulfanylacetyl]-N-(2-pyrrol-1-ylphenyl)pyrrolidine-2-carboxamide | 321311: Displacement of 3H-N-(2-(1H-pyrrol-1-yl)phenyl)-1-(2-(1-methyl-1H-benzo[d]imidazol-2-ylthio)acetyl)pyrrolidine-2-carboxamide from human OX2R expressed in CHO cells | ki | 0.0001 | uM |
| [(2R,5R)-5-[(4-fluoro-3-methylphenoxy)methyl]-2-methylpiperidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone | 1279993: Binding affinity to OX2R (unknown origin) | ki | 0.0001 | uM |
| [(2R,5R)-2-methyl-5-[(4-methylsulfanyl-2-pyridinyl)oxy]piperidin-1-yl]-[2-(triazol-2-yl)phenyl]methanone | 1204737: Displacement of [3H]-(S)-N-(2-(1H-pyrrol-1-yl)phenyl)-1-(2-(1-methyl-1H-benzo[d]imidazol-2-ylthio)acetyl)pyrrolidine-2-carboxamide from human OX2R expressed in CHOK1 cells by radioligand binding assay | ki | 0.0002 | uM |
| (2S)-1-[2-(1-methylbenzimidazol-2-yl)sulfanylacetyl]-N-(2-phenylphenyl)pyrrolidine-2-carboxamide | 1629598: Displacement of [125I]-orexin A from human OX2 receptor expressed in CHO cell membranes after 90 mins by scintillation counting | ki | 0.0002 | uM |
| methyl (2R,3S,5R)-3-(dimethylsulfamoylamino)-2-[[4-(3-fluorophenyl)cyclohexyl]oxymethyl]-5-methylpyrrolidine-1-carboxylate | 1725682: Agonist activity at human recombinant OX2R expressed in CHOK1 cells assessed as increase in intracellular Ca2+ mobilization by measuring IP3 production incubated for 2 hrs by IP-one detection reagent based fluorescence assay | ic50 | 0.0002 | uM |
| methyl (2R,3S,5R)-3-(fluoromethylsulfamoylamino)-2-[[4-(3-fluorophenyl)cyclohexyl]oxymethyl]-5-methylpyrrolidine-1-carboxylate | 1725682: Agonist activity at human recombinant OX2R expressed in CHOK1 cells assessed as increase in intracellular Ca2+ mobilization by measuring IP3 production incubated for 2 hrs by IP-one detection reagent based fluorescence assay | ic50 | 0.0002 | uM |
| (7R,11S)-11-(3,3-difluorobutyl)-8-ethyl-7-methyl-14,17-dioxa-5,8,10,19,20,25-hexazatetracyclo[16.6.1.12,6.019,23]hexacosa-1(24),2(26),3,5,18(25),20,22-heptaen-9-one | 1870720: Agonist activity at human OX2R expressed in CHO cells incubated for 1 to 2 hrs by IP-one detection reagent based fluorescence assay | ec50 | 0.0002 | uM |
| (2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2R)-2-[[(2S,3R)-2-[[(2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-5-carbamimidamido-2-[[(2R)-2-[[(2R)-2-[[(2S)-3-carboxy-2-[[(2S)-1-[(2S)-4-methyl-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]pentanoyl]amino]-5-oxopentanoyl]amino]hexanoyl]amino]-3-hydroxybutanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]acetyl]amino]propanoyl]amino]acetyl]amino]-4-oxobutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]propanoyl]amino]propanoyl]amino]acetyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoic acid | 1827270: Agonist activity at human OX2R expressed in CHO-K1 cells by FLIPR calcium flux assay | ec50 | 0.0002 | uM |
| [(7R)-4-(6-fluoroquinazolin-2-yl)-7-methyl-1,4-diazepan-1-yl]-[2-(triazol-2-yl)phenyl]methanone | 1139800: Displacement of [3H]radioligand from human orexin-2 receptor expressed in CHO cells after 3 hrs by scintillation counting analysis | ki | 0.0002 | uM |
| [(7R)-7-methyl-4-(5-methylthieno[2,3-d]pyrimidin-2-yl)-1,4-diazepan-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone | 1139800: Displacement of [3H]radioligand from human orexin-2 receptor expressed in CHO cells after 3 hrs by scintillation counting analysis | ki | 0.0002 | uM |
| [(2R,5R)-5-[(5-fluoro-2-pyridinyl)oxymethyl]-2-methylpiperidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone | 1124758: Binding affinity to human OX2 receptor in cell membrane by in vitro radioligand binding assay | ki | 0.0002 | uM |
| [(2R,5R)-5-[(5-fluoro-2-pyridinyl)oxymethyl]-2-methylpiperidin-1-yl]-(5-methyl-2-pyrimidin-2-ylphenyl)methanone | 1582240: Displacement of [3H]4-(2,6-Difluoro-4-methoxybenzyl)-2-(5,6-dimethoxypyridin-3-yl)-2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide from human wild-type OX2 receptor expressed in baculovirus infected Sf21 insect cell membranes measured after 90 mins by liquid scintillation counting method | ki | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2R)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[(2R)-1-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-hydroxybutanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]propanoyl]amino]propanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-4-oxobutanoyl]amino]propanoyl]amino]-3-hydroxypropanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-N-[(2S)-1-[[2-[(2S)-2-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]pentanediamide | 256557: Agonist activity against human orexin 2 receptor; EC50; nM | ec50 | 0.0002 | uM |
| (2S)-1-[2-[(6-methyl-1H-benzimidazol-2-yl)sulfanyl]acetyl]-N-(2-pyrrol-1-ylphenyl)pyrrolidine-2-carboxamide | 321311: Displacement of 3H-N-(2-(1H-pyrrol-1-yl)phenyl)-1-(2-(1-methyl-1H-benzo[d]imidazol-2-ylthio)acetyl)pyrrolidine-2-carboxamide from human OX2R expressed in CHO cells | ki | 0.0002 | uM |
| [(2R,5R)-5-(4-methoxyisoquinolin-1-yl)oxy-2-methylpiperidin-1-yl]-[2-(triazol-2-yl)phenyl]methanone | 1190414: Antagonist activity at human OX2R by radioligand displacement assay | ki | 0.0002 | uM |
| [4-(6-fluoroquinazolin-2-yl)-1,4-diazepan-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone | 474967: Binding affinity to OX2 receptor by radioligand displacement assay | ki | 0.0002 | uM |
| [(2S,3R)-3-[(5-fluoro-2-pyridinyl)oxymethyl]-2-methylpiperidin-1-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone | 1453080: Displacement of (2S)-N-(2-pyrrol-1-ylphenyl)-1-[2-[1-(tritritiomethyl)benzimidazol-2-yl]sulfanylacetyl]pyrrolidine-2-carboxamide from recombinant human OX2 receptor expressed in CHO cell membranes after 3 hrs by Topcount method | ki | 0.0002 | uM |
CTD chemical–gene interactions
10 total (human), top 10 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Aflatoxin B1 | decreases methylation, increases methylation | 2 |
| 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone | increases expression | 1 |
| perfluorooctanoic acid | increases expression | 1 |
| aflatoxin B2 | decreases methylation | 1 |
| perfluorooctane sulfonic acid | increases expression | 1 |
| perfluorohexanesulfonic acid | decreases expression | 1 |
| Benzo(a)pyrene | affects methylation | 1 |
| Methylcholanthrene | affects binding, increases reaction | 1 |
| Tamoxifen | decreases expression | 1 |
| Valproic Acid | increases expression | 1 |
ChEMBL screening assays
301 unique, capped per target: 164 binding, 135 functional, 1 admet, 1 toxicity
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1006173 | Functional | Inhibition of human OX2 receptor expressed in CHO cells assessed as intercellular calcium mobilization by FLIPR assay | N-Glycine-sulfonamides as potent dual orexin 1/orexin 2 receptor antagonists. — Bioorg Med Chem Lett |
| CHEMBL1007903 | Binding | Binding affinity to OX2 receptor | Biomedical application of orexin/hypocretin receptor ligands in neuroscience. — J Med Chem |
| CHEMBL3993333 | ADMET | Antagonist activity at human OX2R expressed in CHOK1 cells assessed as inhibition of orexin A-induced intracellular calcium level preincubated for 15 mins followed by orexin A addition by Fura-2-AM dye based fluorescence assay | Design and Synthesis of Potent and Highly Selective Orexin 1 Receptor Antagonists with a Morphinan Skeleton and Their Pharmacologies. — J Med Chem |
Cellosaurus cell lines
4 cell lines: 3 spontaneously immortalized cell line, 1 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_H488 | CHO-K1/OX2 | Spontaneously immortalized cell line | Female |
| CVCL_KX82 | PathHunter CHO-K1 HCRTR2 beta-arrestin | Spontaneously immortalized cell line | Female |
| CVCL_LA50 | PathHunter U2OS HCRTR2 Total GPCR Internalization | Cancer cell line | Female |
| CVCL_ZI72 | GeneBLAzer HCRTR2-Galpha15-NFAT-bla CHO-K1 | Spontaneously immortalized cell line | Female |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Targeted by drugs: Almorexant, Daridorexant, Fazamorexant, Lemborexant, Seltorexant, Suvorexant