Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T97613
(Former ID: TTDI01766)
|
|||||
| Target Name |
Melatonin receptor type 1A (MTNR1A)
|
|||||
| Synonyms |
Mel1a receptor; Mel1AR; Mel-1A-R
Click to Show/Hide
|
|||||
| Gene Name |
MTNR1A
|
|||||
| Target Type |
Successful target
|
[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Insomnia [ICD-11: 7A00-7A0Z] | |||||
| Function |
Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity. High affinity receptor for melatonin.
Click to Show/Hide
|
|||||
| BioChemical Class |
GPCR rhodopsin
|
|||||
| UniProt ID | ||||||
| Sequence |
MQGNGSALPNASQPVLRGDGARPSWLASALACVLIFTIVVDILGNLLVILSVYRNKKLRN
AGNIFVVSLAVADLVVAIYPYPLVLMSIFNNGWNLGYLHCQVSGFLMGLSVIGSIFNITG IAINRYCYICHSLKYDKLYSSKNSLCYVLLIWLLTLAAVLPNLRAGTLQYDPRIYSCTFA QSVSSAYTIAVVVFHFLVPMIIVIFCYLRIWILVLQVRQRVKPDRKPKLKPQDFRNFVTM FVVFVLFAICWAPLNFIGLAVASDPASMVPRIPEWLFVASYYMAYFNSCLNAIIYGLLNQ NFRKEYRRIIVSLCTARVFFVDSSNDVADRVKWKPSPLMTNNNVVKVDSV Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Melatonin | Drug Info | Approved | Insomnia | [2], [3], [4] | |
| 2 | Ramelteon | Drug Info | Approved | Insomnia | [5], [6] | |
| 3 | Tasimelteon | Drug Info | Approved | Insomnia | [7], [3] | |
| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | LY-156735 | Drug Info | Phase 2 | Anxiety disorder | [8], [9] | |
| 2 | Neu-P11 | Drug Info | Phase 2 | Insomnia | [10] | |
| Discontinued Drug(s) | [+] 6 Discontinued Drugs | + | ||||
| 1 | Agomelatine | Drug Info | Withdrawn from market | Major depressive disorder | [11], [12] | |
| 2 | GR-131663 | Drug Info | Terminated | Anxiety disorder | [13] | |
| 3 | GR-133347 | Drug Info | Terminated | Anxiety disorder | [14] | |
| 4 | Luzindole | Drug Info | Terminated | Sleep-wake disorder | [15], [16] | |
| 5 | S-20928 | Drug Info | Terminated | Sleep-wake disorder | [17], [18] | |
| 6 | SL-18.1616 | Drug Info | Terminated | Insomnia | [19] | |
| Mode of Action | [+] 5 Modes of Action | + | ||||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Melatonin | Drug Info | [1], [20], [21] | |||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | Ramelteon | Drug Info | [22], [23] | |||
| 2 | GR-131663 | Drug Info | [27] | |||
| 3 | GR-133347 | Drug Info | [28] | |||
| 4 | Luzindole | Drug Info | [29] | |||
| 5 | S-20928 | Drug Info | [30] | |||
| Agonist | [+] 30 Agonist drugs | + | ||||
| 1 | Tasimelteon | Drug Info | [7] | |||
| 2 | LY-156735 | Drug Info | [24] | |||
| 3 | Neu-P11 | Drug Info | [25] | |||
| 4 | Agomelatine | Drug Info | [26] | |||
| 5 | SL-18.1616 | Drug Info | [31] | |||
| 6 | 2-iodo-melatonin | Drug Info | [34], [35] | |||
| 7 | 2-methoxy-alpha,beta-didehydro-agomelatine | Drug Info | [36] | |||
| 8 | 2-[125I]melatonin | Drug Info | [37] | |||
| 9 | 5-HEAT | Drug Info | [40] | |||
| 10 | 5-methoxy-luzindole | Drug Info | [37] | |||
| 11 | 6-Cl-MLT | Drug Info | [34] | |||
| 12 | 6-hydroxymelatonin | Drug Info | [34] | |||
| 13 | AAE-M-PBP-amine | Drug Info | [42] | |||
| 14 | BOMPPA | Drug Info | [44] | |||
| 15 | CBOBNEA | Drug Info | [45] | |||
| 16 | CIFEA | Drug Info | [46] | |||
| 17 | difluoroagomelatine | Drug Info | [48] | |||
| 18 | EFPPEA | Drug Info | [49] | |||
| 19 | GR 128107 | Drug Info | [50] | |||
| 20 | GR 196429 | Drug Info | [51] | |||
| 21 | IIK7 | Drug Info | [52] | |||
| 22 | isoamyl-agomelatine | Drug Info | [48] | |||
| 23 | S24014 | Drug Info | [56] | |||
| 24 | S24773 | Drug Info | [56] | |||
| 25 | S26284 | Drug Info | [56] | |||
| 26 | UCM 765 | Drug Info | [58] | |||
| 27 | UCM 793 | Drug Info | [58] | |||
| 28 | [125I]DIV880 | Drug Info | [59] | |||
| 29 | [125I]S70254 | Drug Info | [59] | |||
| 30 | [125I]SD6 | Drug Info | [59] | |||
| Antagonist | [+] 9 Antagonist drugs | + | ||||
| 1 | (hydroxymethylphenyl)agomelatine | Drug Info | [32] | |||
| 2 | 2-(indolin-1yl)-melatonin | Drug Info | [33] | |||
| 3 | 4P-PDOT | Drug Info | [39] | |||
| 4 | DH97 | Drug Info | [47] | |||
| 5 | K185 | Drug Info | [52] | |||
| 6 | S22153 | Drug Info | [56] | |||
| 7 | S26131 | Drug Info | [56] | |||
| 8 | UCM 549 | Drug Info | [57] | |||
| 9 | UCM 724 | Drug Info | [57] | |||
| Inhibitor | [+] 17 Inhibitor drugs | + | ||||
| 1 | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [38] | |||
| 2 | 5-methoxycarbonylamino-N-acetyltryptamine | Drug Info | [41] | |||
| 3 | Beta,beta-dimethylmelatonin | Drug Info | [43] | |||
| 4 | Beta-methylmelatonin | Drug Info | [43] | |||
| 5 | N-(2,3,4,9-Tetrahydro-1H-carbazol-3-yl)-acetamide | Drug Info | [53] | |||
| 6 | N-(2,3-Dihydro-1H-phenalen-2-yl)-acetamide | Drug Info | [54] | |||
| 7 | N-(2-(5-methoxybenzofuran-3-yl)ethyl)acetamide | Drug Info | [41] | |||
| 8 | N-(3-(2,5-dimethoxyphenyl)propyl)acetamide | Drug Info | [55] | |||
| 9 | N-(3-(2-ethoxy-5-methoxyphenyl)propyl)acetamide | Drug Info | [55] | |||
| 10 | N-(3-(2-hydroxy-5-methoxyphenyl)propyl)acetamide | Drug Info | [55] | |||
| 11 | N-(3-(3-methoxyphenyl)-3-phenylallyl)acetamide | Drug Info | [33] | |||
| 12 | N-(3-(3-methoxyphenyl)propyl)acetamide | Drug Info | [55] | |||
| 13 | N-(3-(3-methoxyphenyl)propyl)propionamide | Drug Info | [55] | |||
| 14 | N-(3-(4-hydroxy-3-methoxyphenyl)propyl)acetamide | Drug Info | [55] | |||
| 15 | N-(3-(5-methoxy-2-propoxyphenyl)propyl)acetamide | Drug Info | [55] | |||
| 16 | N-acetylserotonin | Drug Info | [54] | |||
| 17 | UCM-454 | Drug Info | [33] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: Ramelteon | Ligand Info | |||||
| Structure Description | human melatonin receptor MT1 - Gi1 complex | PDB:7DB6 | ||||
| Method | Electron microscopy | Resolution | 3.30 Å | Mutation | No | [60] |
| PDB Sequence |
RPSWLASALA
31 CVLIFTIVVD41 ILGNLLVILS51 VYRNKKLRNA61 GNIFVVSLAV71 ADLVVAIYPY 81 PLVLMSIFNN91 GWNLGYLHCQ101 VSGFLMGLSV111 IGSIFNITGI121 AINRYCYICH 131 SLKYDKLYSS141 KNSLCYVLLI151 WLLTLAAVLP161 NLRAGTLQYD171 PRIYSCTFAQ 181 SVSSAYTIAV191 VVFHFLVPMI201 IVIFCYLRIW211 ILVLQVRQRV221 PQDFRNFVTM 240 FVVFVLFAIC250 WAPLNFIGLA260 VASDPASMVP270 RIPEWLFVAS280 YYMAYFNSCL 290 NAIIYGLLNQ300 NFRKEY
|
|||||
|
|
GLY104
3.609
MET107
4.366
GLY108
3.521
VAL111
3.772
ILE112
3.698
ALA158
4.696
VAL159
4.389
LEU163
3.453
LEU168
4.076
THR178
4.907
PHE179
3.580
|
|||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 2-iodo-melatonin | Ligand Info | |||||
| Structure Description | Melatonin receptor1-2-Iodomelatonin-Gicomplex | PDB:7VGY | ||||
| Method | Electron microscopy | Resolution | 3.10 Å | Mutation | No | [61] |
| PDB Sequence |
PSWLASALAC
32 VLIFTIVVDI42 LGNLLVILSV52 YRNKKLRNAG62 NIFVVSLAVA72 DLVVAIYPYP 82 LVLMSIFNNG92 WNLGYLHCQV102 SGFLMGLSVI112 GSIFNITGIA122 INRYCYICHS 132 LKYDKLYSSK142 NSLCYVLLIW152 LLTLAAVLPN162 LRAGTLQYDP172 RIYSCTFAQS 182 VSSAYTIAVV192 VFHFLVPMII202 VIFCYLRIWI212 LVLQVRQRVK222 PFRNFVTMFV 242 VFVLFAICWA252 PLNFIGLAVA262 SDPASMVPRI272 PEWLFVASYY282 MAYFNSCLNA 292 IIYGLLNQNF302 RKEYRRIIVS312 L
|
|||||
|
|
GLY104
4.303
MET107
3.517
GLY108
3.540
VAL111
3.869
ILE112
3.877
ALA158
4.259
VAL159
3.960
ASN162
3.649
LEU168
4.053
PHE179
3.535
GLN181
3.388
|
|||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
|
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
|
| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Circadian entrainment | hsa04713 | Affiliated Target |
|
| Class: Organismal Systems => Environmental adaptation | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Drug Property Profile of Target | Top | |
|---|---|---|
| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
|
|
||
| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
|
|
||
| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
|
|
||
| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Circadian entrainment | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Class A/1 (Rhodopsin-like receptors) | |||||
| 2 | G alpha (i) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | GPCRs, Class A Rhodopsin-like | |||||
| 2 | Small Ligand GPCRs | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | The human MT1 melatonin receptor stimulates cAMP production in the human neuroblastoma cell line SH-SY5Y cells via a calcium-calmodulin signal transduction pathway. J Neuroendocrinol. 2005 Mar;17(3):170-8. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 224). | |||||
| REF 3 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 4 | Melatonin and melatonergic drugs on sleep: possible mechanisms of action. Int J Neurosci. 2009;119(6):821-46. | |||||
| REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1356). | |||||
| REF 6 | Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62. | |||||
| REF 7 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7393). | |||||
| REF 8 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1351). | |||||
| REF 9 | Melatonin and its receptors: a new class of sleep-promoting agents. J Clin Sleep Med. 2007 Aug 15;3(5 Suppl):S17-23. | |||||
| REF 10 | ClinicalTrials.gov (NCT01489969) Sleep Laboratory Study to Investigate the Safety and Efficacy of Neu-P11 in Primary Insomnia Patients. U.S. National Institutes of Health. | |||||
| REF 11 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 198). | |||||
| REF 12 | Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92. | |||||
| REF 13 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003455) | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003420) | |||||
| REF 15 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1363). | |||||
| REF 16 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000705) | |||||
| REF 17 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1360). | |||||
| REF 18 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006913) | |||||
| REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014349) | |||||
| REF 20 | Coexpression of MT1 and RORalpha1 melatonin receptors in the Syrian hamster Harderian gland. J Pineal Res. 2005 Aug;39(1):21-6. | |||||
| REF 21 | Pharmacological characterization of human recombinant melatonin mt(1) and MT(2) receptors. Br J Pharmacol. 2000 Mar;129(5):877-86. | |||||
| REF 22 | MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85. | |||||
| REF 23 | Ramelteon: a melatonin receptor agonist for the treatment of insomnia. J Postgrad Med. 2008 Jan-Mar;54(1):45-8. | |||||
| REF 24 | Melatonin and sleep in aging population. Exp Gerontol. 2005 Dec;40(12):911-25. | |||||
| REF 25 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 288). | |||||
| REF 26 | Melatonin receptor agonists: SAR and applications to the treatment of sleep-wake disorders. Curr Top Med Chem. 2008;8(11):954-68. | |||||
| REF 27 | Novel non-indolic melatonin receptor agonists differentially entrain endogenous melatonin rhythm and increase its amplitude. Eur J Pharmacol. 1999 Oct 15;382(3):157-66. | |||||
| REF 28 | US patent application no. 5,151,446, Substituted 2-amidotetralins as melatonin agonists and antagonists. | |||||
| REF 29 | Luzindole (N-0774): a novel melatonin receptor antagonist. J Pharmacol Exp Ther. 1988 Sep;246(3):902-10. | |||||
| REF 30 | Effects of two melatonin analogues, S-20098 and S-20928, on melatonin receptors in the pars tuberalis of the rat. J Pineal Res. 1998 Oct;25(3):172-6. | |||||
| REF 31 | US patent application no. 2005,016,4987, Melatonin combination therapy for improving sleep quality. | |||||
| REF 32 | Synthesis of 3-phenylnaphthalenic derivatives as new selective MT(2) melatoninergic ligands. Bioorg Med Chem. 2008 Sep 15;16(18):8339-48. | |||||
| REF 33 | 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues: a novel class of MT2-selective melatonin receptor antagonists. J Med Chem. 2009 Feb 12;52(3):826-33. | |||||
| REF 34 | Characterization of a retinal melatonin receptor. J Pharmacol Exp Ther. 1985 Aug;234(2):395-401. | |||||
| REF 35 | Synthesis of nitroindole derivatives with high affinity and selectivity for melatoninergic binding sites MT(3). J Med Chem. 2002 Apr 25;45(9):1853-9. | |||||
| REF 36 | Synthesis of new N-(arylcyclopropyl)acetamides and N-(arylvinyl)acetamides as conformationally-restricted ligands for melatonin receptors. Bioorg Med Chem Lett. 2013 Jan 15;23(2):430-4. | |||||
| REF 37 | Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Naunyn Schmiedebergs Arch Pharmacol. 1997 Mar;355(3):365-75. | |||||
| REF 38 | Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97. | |||||
| REF 39 | Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms. FASEB J. 1998 Sep;12(12):1211-20. | |||||
| REF 40 | A new melatonin receptor ligand with mt1-agonist and MT2-antagonist properties. J Pineal Res. 2000 Nov;29(4):234-40. | |||||
| REF 41 | Design and synthesis of benzofuranic derivatives as new ligands at the melatonin-binding site MT3. Bioorg Med Chem. 2008 May 1;16(9):4954-62. | |||||
| REF 42 | MT1-selective melatonin receptor ligands: synthesis, pharmacological evaluation, and molecular dynamics investigation of N-{[(3-O-substituted)anilino]alkyl}amides. ChemMedChem. 2012 Nov;7(11):1954-64. | |||||
| REF 43 | Mapping the melatonin receptor. 7. Subtype selective ligands based on beta-substituted N-acyl-5-methoxytryptamines and beta-substituted N-acyl-5-me... J Med Chem. 2006 Jun 15;49(12):3509-19. | |||||
| REF 44 | Development of substituted N-[3-(3-methoxylphenyl)propyl] amides as MT(2)-selective melatonin agonists: improving metabolic stability. Bioorg Med Chem. 2013 Jan 15;21(2):547-52. | |||||
| REF 45 | Design, synthesis and pharmacological evaluation of novel naphthalenic derivatives as selective MT(1) melatoninergic ligands. Bioorg Med Chem. 2010 May 15;18(10):3426-36. | |||||
| REF 46 | 1,6-Dihydro-2H-indeno[5,4-b]furan derivatives: design, synthesis, and pharmacological characterization of a novel class of highly potent MT selective agonists. J Med Chem. 2011 May 12;54(9):3436-44. | |||||
| REF 47 | Comparison of the structure-activity relationships of melatonin receptor agonists and antagonists: lengthening the N-acyl side-chain has differing effects on potency on Xenopus melanophores. Naunyn Schmiedebergs Arch Pharmacol. 1998 Nov;358(5):522-8. | |||||
| REF 48 | Design, synthesis and pharmacological evaluation of new series of naphthalenic analogues as melatoninergic (MT1/MT2) and serotoninergic 5-HT2C dual ligands (I). Eur J Med Chem. 2012 Mar;49:310-23. | |||||
| REF 49 | Synthesis of a novel series of tricyclic dihydrofuran derivatives: discovery of 8,9-dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridines as melatonin receptor (MT1/MT2) ligands. J Med Chem. 2011 Jun 23;54(12):4207-18. | |||||
| REF 50 | The putative melatonin receptor antagonist GR128107 is a partial agonist on Xenopus laevis melanophores. Br J Pharmacol. 1999 Mar;126(5):1237-45. | |||||
| REF 51 | GR196429: a nonindolic agonist at high-affinity melatonin receptors. J Pharmacol Exp Ther. 1998 Jun;285(3):1239-45. | |||||
| REF 52 | Mapping the melatonin receptor. 6. Melatonin agonists and antagonists derived from 6H-isoindolo[2,1-a]indoles, 5,6-dihydroindolo[2,1-a]isoquinolines, and 6,7-dihydro-5H-benzo[c]azepino[2,1-a]indoles.J Med Chem. 2000 Mar 23;43(6):1050-61. | |||||
| REF 53 | Mapping the melatonin receptor. 2. synthesis and biological activity of indole derived melatonin analogues with restricted conformations of the C-3 amidoethane side chain, Bioorg. Med. Chem. Lett. 4(13):1559-1564 (1994). | |||||
| REF 54 | Synthesis of 2-amido-2,3-dihydro-1H-phenalene derivatives as new conformationally restricted ligands for melatonin receptors. J Med Chem. 1996 Aug 2;39(16):3089-95. | |||||
| REF 55 | Synthesis of substituted N-[3-(3-methoxyphenyl)propyl] amides as highly potent MT(2)-selective melatonin ligands. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2582-5. | |||||
| REF 56 | New selective ligands of human cloned melatonin MT1 and MT2 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2003 Jun;367(6):553-61. | |||||
| REF 57 | Synthesis, enantiomeric resolution, and structure-activity relationship study of a series of 10,11-dihydro-5H-dibenzo[a,d]cycloheptene MT2 receptor antagonists. ChemMedChem. 2007 Dec;2(12):1741-9. | |||||
| REF 58 | N-(substituted-anilinoethyl)amides: design, synthesis, and pharmacological characterization of a new class of melatonin receptor ligands. J Med Chem. 2007 Dec 27;50(26):6618-26. | |||||
| REF 59 | New radioligands for describing the molecular pharmacology of MT1 and MT2 melatonin receptors. Int J Mol Sci. 2013 Apr 25;14(5):8948-62. | |||||
| REF 60 | Cryo-EM structure of the human MT(1)-G(i) signaling complex. Nat Struct Mol Biol. 2021 Aug;28(8):694-701. | |||||
| REF 61 | Structural basis of the ligand binding and signaling mechanism of melatonin receptors. Nat Commun. 2022 Jan 24;13(1):454. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.