23-Dimensional Molecular Structure for the Life Science320084-712-4230-3451501

Hideaki Umeyama, Ph.D., ProfessorSchool of Pharmacy, Kitasato University5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japanphone : +81-3-5791-6330 fax : +81-3-3446-9553e-mail:umeyamah@pharm.kitasato-u.ac.jp

http://famshelp.gsc.riken.jp/famsbase/index.htmlhttp://www.pd-fams.com/index_ja.htmlhttp://www.pharm.kitasato-u.ac.jp/bmd/files/achievement.htmlhttp://www.pharm.kitasato-u.ac.jp/bmd/http://h20pharm.kitasato-u.websyllabus.jp/content/versionview/235/29

ramelteon(Rozerem)2005722FDA)ramelteon

GABA-BZ

ramelteon(Rozerem)Melatonin receptorsML3 ML1 ML2

20052920044200

ramelteon(Rozerem)

Ramelteon :melatonin receptor agonistRamelteon is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and selectivity over the MT3 receptor. Ramelteon demonstrates full agonist activity in vitro in cells expressing human MT1 or MT2 receptors, and high selectivity for human MT 1 and MT2 receptors compared to the MT3 receptor.

RamelteonIUPAC Name: N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzoxol-8-yl]ethyl]propanamide Canonical SMILES: CCC(=O)NCCC1CCC2=C1C3=C(C=C2)OCC3 Isomeric SMILES: CCC(=O)NCC[C@@H]1CCC2=C1C3=C(C=C2)OCC3 InChI: InChI=1/C16H21NO2/c1-2-15(18)17-9-7-12-4-3-11-5-6-14-13(16(11)12)8-10-19-14/h5-6,12H,2-4,7-10H2,1H3,(H,17,18)/t12-/m0/s1/f/h17H

ML1 ML2

GABA-BZ

GABA-BZ

MelatoninMelatonin, 5-methoxy-N-acetyltryptamine, is a naturally occurring hormone found in most animals and some of other living organisms, including (algae) and humans, at levels that vary in a daily cycle. It plays a role in the regulation of theCircadian rhythm of several biological functions.[2] Many biological effects of melatonin are produced through activation of melatonin receptors.

,

MelatoninIUPAC Name: N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide Canonical SMILES: CC(=O)NCCC1=CNC2=C1C=C(C=C2)OC InChI: InChI=1/C13H16N2O2/c1-9(16)14-6-5-10-8-15-13-4-3-11(17-2)7-12(10)13/h3-4,7-8,15H,5-6H2,1-2H3,(H,14,16)/f/h14H

Melatonin receptor type 1A (Mel-1A-R) (Mel1a melatonin receptor) [FUNCTION] High affinity receptor for melatonin. Likely to mediates 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.

Circadian rhythmReproductive Science Melatonin

[SUBCELLULAR LOCATION] Cell membrane; Multi-pass membrane protein.

[TISSUE SPECIFICITY] Hippocampus. hippocampus

[SIMILARITY] Belongs to the G-protein coupled receptor 1 family. [WEB RESOURCE] Name=Wikipedia; Note=Melatonin receptor entry; URL='http://en.wikipedia.org/wiki/Melatonin_receptor'.

P48039 MTR1A_HUMANP49286 MTR1B_HUMANQ13585 MTR1L_HUMAN

Melatonin receptor type 1A (Mel-1A-R) (Mel1a melatonin receptor) [FUNCTION] High affinity receptor for melatonin. Likely to mediates 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.

[SUBCELLULAR LOCATION] Cell membrane; Multi-pass membrane protein.

[TISSUE SPECIFICITY] Hippocampus. hippocampus

[SIMILARITY] Belongs to the G-protein coupled receptor 1 family. [WEB RESOURCE] Name=Wikipedia; Note=Melatonin receptor entry; URL='http://en.wikipedia.org/wiki/Melatonin_receptor'.

P48039MTR1A_HUMAN >gi|1346544|sp|P48039.1|MTR1A_HUMAN Melatonin receptor type 1A (Mel-1A-R) (Mel1a melatonin receptor)MQGNGSALPNASQPVLRGDGARPSWLASALACVLIFTIVVDILGNLLVILSVYRNKKLRNAGNIFVVSLAVADLVVAIYPYPLVLMSIFNNGWNLGYLHCQVSGFLMGLSVIGSIFNITGIAINRYCYICHSLKYDKLYSSKNSLCYVLLIWLLTLAAVLPNLRAGTLQYDPRIYSCTFAQSVSSAYTIAVVVFHFLVPMIIVIFCYLRIWILVLQVRQRVKPDRKPKLKPQDFRNFVTMFVVFVLFAICWAPLNFIGLAVASDPASMVPRIPEWLFVASYYMAYFNSCLNAIIYGLLNQNFRKEYRRIIVSLCTARVFFVDSSNDVADRVKWKPSPLMTNNNVVKVDSV

Sequence identities of melatonin receptors 1e-100(350,1-350)100%ref|NP_005949.1| melatonin receptor 1A [Homo sapiens] gb|AAH74947.1| Melatonin receptor 1A [Homo sapiens] gb|AAH74946.1| Melatonin receptor 1A [Homo sapiens] dbj|BAA85303.1| melatonin 1a receptor [Homo sapiens] sp|P48039 sp ncbi|MTR1A_HUMAN Melatonin receptor type 1A (Mel-1A-R) (Mel1a melatonin receptor) gb|AAB17720.1| Mel-1a melatonin receptor; Length=350

7e-83(319,23-341)62%ref|NP_005950.1| melatonin receptor 1B [Homo sapiens] gb|AAH69163.1| Melatonin receptor 1B [Homo sapiens] gb|AAS00461.1| melatonin receptor 1B [Homo sapiens] dbj|BAA92315.1| melatonin 1b receptor [Homo sapiens] sp|P49286 sp ncbi|MTR1B_HUMAN Melatonin receptor type 1B (Mel-1B-R) (Mel1b melatonin receptor) gb|AAC50612.1| Mel1b-melatonin receptor; Length=362

1e-86(296,24-319)52%ref|NP_004215.1| G protein-coupled receptor 50 [Homo sapiens] sp|Q13585 sp ncbi|MTR1L_HUMAN Melatonin-related receptor (G protein-coupled receptor 50) (H9) gb|AAC50614.1| melatonin-related receptor; Length=613

5e-47(300,7-306)25%gb|AAH13780.1| Adenosine A2a receptor [Homo sapiens] ref|NP_000666.2| adenosine A2a receptor [Homo sapiens] gb|AAN01273.1| adenosine receptor A2a [Homo sapiens] gb|AAP35645.1| adenosine A2a receptor [Homo sapiens] gb|AAA83270.1| A2a adenosine receptor subtype [Homo sapiens] emb|CAA48504.1| A2a adenosine receptor [Homo sapiens] gb|AAX41777.1| adenosine A2a receptor [synthetic construct] emb|CAG30253.1| ADORA2A [Homo sapiens] sp|P29274 sp ncbi|AA2AR_HUMAN Adenosine A2a receptor; Length=412

Ramelteon; RozeremRamelteon; Rozerem; Rozerem (TN) ...

MW: 259.343440 g/mol | MF: C16H21NO2IUPAC Name: N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzoxol-8-yl]ethyl]propanamide Canonical SMILES: CCC(=O)NCCC1CCC2=C1C3=C(C=C2)OCC3 Isomeric SMILES: CCC(=O)NCC[C@@H]1CCC2=C1C3=C(C=C2)OCC3

Melatonin; Melatonine CID: 896 IUPAC: N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide MW: 232.278340 g/mol | MF: C13H16N2O2

IUPAC Name: N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide Canonical SMILES: CC(=O)NCCC1=CNC2=C1C=C(C=C2)OC

Molecular Weight: 232.27834 g/mol Molecular Formula: C13H16N2O2 XLogP: 1.6 Hydrogen Bond Donor Count: 2 Hydrogen Bond Acceptor Count: 3 Rotatable Bond Count: 4 Tautomer Count: 2

Melatonin receptor type 1B (Mel-1B-R)>gi|1346548|sp|P49286.1|MTR1B_HUMAN Melatonin receptor type 1B (Mel-1B-R) (Mel1b melatonin receptor)MSENGSFANCCEAGGWAVRPGWSGAGSARPSRTPRPPWVAPALSAVLIVTTAVDVVGNLLVILSVLRNRKLRNAGNLFLVSLALADLVVAFYPYPLILVAIFYDGWALGEEHCKASAFVMGLSVIGSVFNITAIAINRYCYICHSMAYHRIYRRWHTPLHICLIWLLTVVALLPNFFVGSLEYDPRIYSCTFIQTASTQYTAAVVVIHFLLPIAVVSFCYLRIWVLVLQARRKAKPESRLCLKPSDLRSFLTMFVVFVIFAICWAPLNCIGLAVAINPQEMAPQIPEGLFVTSYLLAYFNSCLNAIVYGLLNQNFRREYKRILLALWNPRHCIQDASKGSHAEGLQSPAPPIIGVQHQADAL

Sequence identities of Melatonin receptors 5e-94(362,1-362)100%ref|NP_005950.1| melatonin receptor 1B [Homo sapiens] gb|AAH69163.1| Melatonin receptor 1B [Homo sapiens] gb|AAS00461.1| melatonin receptor 1B [Homo sapiens] dbj|BAA92315.1| melatonin 1b receptor [Homo sapiens] sp|P49286 sp ncbi|MTR1B_HUMAN Melatonin receptor type 1B (Mel-1B-R) (Mel1b melatonin receptor) gb|AAC50612.1| Mel1b-melatonin receptor; Length=362

3e-86(337,9-345)59%ref|NP_005949.1| melatonin receptor 1A [Homo sapiens] gb|AAH74947.1| Melatonin receptor 1A [Homo sapiens] gb|AAH74946.1| Melatonin receptor 1A [Homo sapiens] dbj|BAA85303.1| melatonin 1a receptor [Homo sapiens] sp|P48039 sp ncbi|MTR1A_HUMAN Melatonin receptor type 1A (Mel-1A-R) (Mel1a melatonin receptor) gb|AAB17720.1| Mel-1a melatonin receptor; Length=350

4e-85(315,1-315)47%ref|NP_004215.1| G protein-coupled receptor 50 [Homo sapiens] sp|Q13585 sp ncbi|MTR1L_HUMAN Melatonin-related receptor (G protein-coupled receptor 50) (H9) gb|AAC50614.1| melatonin-related receptor; Length=613

Melatonin-related receptor (G protein-coupled receptor 50)>gi|2494977|sp|Q13585.1|MTR1L_HUMAN Melatonin-related receptor (G protein-coupled receptor 50) (H9)MGPTLAVPTPYGCIGCKLPQPEYPPALIIFMFCAMVITIVVDLIGNSMVILAVTKNKKLRNSGNIFVVSLSVADMLVAIYPYPLMLHAMSIGGWDLSQLQCQMVGFITGLSVVGSIFNIVAIAINRYCYICHSLQYERIFSVRNTCIYLVITWIMTVLAVLPNMYIGTIEYDPRTYTCIFNYLNNPVFTVTIVCIHFVLPLLIVGFCYVRIWTKVLAARDPAGQNPDNQLAEVRNFLTMFVIFLLFAVCWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREYWTIFHAMRHPIIFFPGLISDIREMQEARTLARARAHARDQAREQDRAHACPAVEETPMNVRNVPLPGDAAAGHPDRASGHPKPHSRSSSAYRKSASTHHKSVFSHSKAASGHLKPVSGHSKPASGHPKSATVYPKPASVHFKGDSVHFKGDSVHFKPDSVHFKPASSNPKPITGHHVSAGSHSKSAFSAATSHPKPIKPATSHAEPTTADYPKPATTSHPKPAAADNPELSASHCPEIPAIAHPVSDDSDLPESASSPAAGPTKPAASQLESDTIADLPDPTVVTTSTNDYHDVVVVDVEDDPDEMAV

Sequence Identities of MTR1L Melatonin-related receptor 0.0(613,1-613)100%ref|NP_004215.1| G protein-coupled receptor 50 [Homo sapiens] sp|Q13585 sp ncbi|MTR1L_HUMAN Melatonin-related receptor (G protein-coupled receptor 50) (H9) gb|AAC50614.1| melatonin-related receptor; Length=613FAMD

1e-101(328,22-349)47%ref|NP_005949.1| melatonin receptor 1A [Homo sapiens] gb|AAH74947.1| Melatonin receptor 1A [Homo sapiens] gb|AAH74946.1| Melatonin receptor 1A [Homo sapiens] dbj|BAA85303.1| melatonin 1a receptor [Homo sapiens] sp|P48039 sp ncbi|MTR1A_HUMAN Melatonin receptor type 1A (Mel-1A-R) (Mel1a melatonin receptor) gb|AAB17720.1| Mel-1a melatonin receptor; Length=350FAMD

1e-92(332,20-351)44%ref|NP_005950.1| melatonin receptor 1B [Homo sapiens] gb|AAH69163.1| Melatonin receptor 1B [Homo sapiens] gb|AAS00461.1| melatonin receptor 1B [Homo sapiens] dbj|BAA92315.1| melatonin 1b receptor [Homo sapiens] sp|P49286 sp ncbi|MTR1B_HUMAN Melatonin receptor type 1B (Mel-1B-R) (Mel1b melatonin receptor) gb|AAC50612.1| Mel1b-melatonin receptor; Length=362FAMD

-

Serotonin N-acetyltransferase (Aralkylamine N-acetyltransferase) (AA-NAT) (Serotonin acetylase) (NIH)-

Serotonin N-acetyltransferase [FUNCTION] Catalyzes the N-acetylation of serotonin intoN-acetylserotonin. [CATALYTIC ACTIVITY] Acetyl-CoA + a 2-arylethylamine = CoA + AnN-acetyl-2-arylethylamine.>gi|11387096|sp|Q16613.1|SNAT_HUMAN Serotonin N-acetyltransferase (Aralkylamine N-acetyltransferase) (AA-NAT) (Serotonin acetylase)MSTQSTHPLKPEAPRLPPGIPESPSCQRRHTLPASEFRCLTPEDAVSAFEIEREAFISVLGVCPLYLDEIRHFLTLCPELSLGWFEEGCLVAFIIGSLWDKERLMQESLTLHRSGGHIAHLHVLAVHRAFRQQGRGPILLWRYLHHLGSQPAVRRAALMCEDALVPFYERFSFHAVGPCAITVGSLTFMELHCSLRGHPFLRRNSGC

Ramelteon:Drug interactions Ramelteon should be administered with caution in patients taking other CYP1A2 inhibitors, strong CYP3A4 inhibitors such as ketoconazole, and strong CYP2C9 inhibitors such as fluconazole.Efficacy may be reduced when ramelteon is used in combination with potent CYP enzyme inducers such as rifampin, since ramelteon concentrations may be decreased.

P05177.3|CP1A2_HUMAN Cytochrome P450 1A2 (CYPIA2)>gi|117144|sp|P05177.3|CP1A2_HUMAN Cytochrome P450 1A2 (CYPIA2) (P450-P3) (P(3)450) (P450 4)MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKNPHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDGQSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELMAGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFPILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGNLIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLSDRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPELWEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLEFSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN

P05177.3|CP1A2_HUMANP05177CP1A2_HUMAN

gi|116241312|sp|P08684.4|CP3A4_HUMAN Cytochrome P450 3A4>gi|116241312|sp|P08684.4|CP3A4_HUMAN Cytochrome P450 3A4 (Quinine 3-monooxygenase) (CYPIIIA4) (Nifedipine oxidase) (Cytochrome P450 3A3) (CYPIIIA3) (HLp) (Taurochenodeoxycholate 6-alpha-hydroxylase) (NF-25) (P450-PCN1)MALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFDMECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIAEDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSMDVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVFPREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSIIFIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVNETLRLFPIAMRLERVCKKDVEINGMFIPKGVVVMIPSYALHRDPKYWTEPEKFLPERFSKKNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGGLLQPEKPVVLKVESRDGTVSGA

sp|P11712.3|CP2C9_HUMAN Cytochrome P450 2C9>gi|6686268|sp|P11712.3|CP2C9_HUMAN Cytochrome P450 2C9 ((R)-limonene 6-monooxygenase) ((S)-limonene

6-monooxygenase) ((S)-limonene 7-monooxygenase) (CYPIIC9) (P450 PB-1) (P450 MP-4/MP-8) (S-mephenytoin

4-hydroxylase) (P-450MP)MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPV

23-Dimensional Molecular Structure for the Life Science320084-712-41501

Hideaki Umeyama, Ph.D., ProfessorSchool of Pharmacy, Kitasato University5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japanphone : +81-3-5791-6330 fax : +81-3-3446-9553e-mail:umeyamah@pharm.kitasato-u.ac.jp

http://famshelp.gsc.riken.jp/famsbase/index.htmlhttp://www.pd-fams.com/index_ja.htmlhttp://www.pharm.kitasato-u.ac.jp/bmd/files/achievement.htmlhttp://www.pharm.kitasato-u.ac.jp/bmd/http://h20pharm.kitasato-u.websyllabus.jp/content/versionview/235/29