Target Information
| Target General Information | Top | |||||
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| Target ID |
T59679
(Former ID: TTDS00107)
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| Target Name |
5-HT 4 receptor (HTR4)
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| Synonyms |
Serotonin receptor 4; 5-hydroxytryptamine receptor 4; 5-HT4 receptor; 5-HT4; 5-HT-4
Click to Show/Hide
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| Gene Name |
HTR4
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Gastro-oesophageal reflux disease [ICD-11: DA22] | |||||
| 2 | Irritable bowel syndrome [ICD-11: DD91] | |||||
| Function |
The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen.
Click to Show/Hide
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MDKLDANVSSEEGFGSVEKVVLLTFLSTVILMAILGNLLVMVAVCWDRQLRKIKTNYFIV
SLAFADLLVSVLVMPFGAIELVQDIWIYGEVFCLVRTSLDVLLTTASIFHLCCISLDRYY AICCQPLVYRNKMTPLRIALMLGGCWVIPTFISFLPIMQGWNNIGIIDLIEKRKFNQNSN STYCVFMVNKPYAITCSVVAFYIPFLLMVLAYYRIYVTAKEHAHQIQMLQRAGASSESRP QSADQHSTHRMRTETKAAKTLCIIMGCFCLCWAPFFVTNIVDPFIDYTVPGQVWTAFLWL GYINSGLNPFLYAFLNKSFRRAFLIILCCDDERYRRPSILGQTVPCSTTTINGSTHVLRD AVECGGQWESQCHPPATSPLVAAQPSDT Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 4 Approved Drugs | + | ||||
| 1 | Cisapride | Drug Info | Approved | Gastroesophageal reflux disease | [2], [3] | |
| 2 | HTF 919 | Drug Info | Approved | Constipation | [4], [5] | |
| 3 | R0-93877 | Drug Info | Approved | Irritable bowel syndrome | [6] | |
| 4 | Tegaserod | Drug Info | Approved | Irritable bowel syndrome | [4] | |
| Clinical Trial Drug(s) | [+] 16 Clinical Trial Drugs | + | ||||
| 1 | Renzapride | Drug Info | Phase 3 | Irritable bowel syndrome | [7], [8] | |
| 2 | DSP-6952 | Drug Info | Phase 2 | Constipation | [11] | |
| 3 | Lintopride | Drug Info | Phase 2 | Nausea | [12] | |
| 4 | PF-885706 | Drug Info | Phase 2 | Gastroesophageal reflux disease | [13] | |
| 5 | PRX-3140 | Drug Info | Phase 2 | Post-traumatic stress disorder | [14] | |
| 6 | SB-207266A | Drug Info | Phase 2 | Irritable bowel syndrome | [15] | |
| 7 | SPD-557 | Drug Info | Phase 2 | Diabetic gastroparesis | [16] | |
| 8 | TD-5108 | Drug Info | Phase 2 | Gastroparesis | [17], [18] | |
| 9 | TD-8954 | Drug Info | Phase 2 | Gastrointestinal disease | [19] | |
| 10 | YKP-GI | Drug Info | Phase 2 | Constipation | [20], [21] | |
| 11 | BIMU-1 | Drug Info | Phase 1 | Cognitive impairment | [22], [23] | |
| 12 | DA-6886 | Drug Info | Phase 1 | Irritable bowel syndrome | [24] | |
| 13 | M-0004 | Drug Info | Phase 1 | Gastroesophageal reflux disease | [25] | |
| 14 | PF-04995274 | Drug Info | Phase 1 | Alzheimer disease | [26] | |
| 15 | SER-101 | Drug Info | Phase 1 | Congestive heart failure | [27] | |
| 16 | SUVN-D4010 | Drug Info | Phase 1 | Alzheimer disease | [28], [29] | |
| Discontinued Drug(s) | [+] 7 Discontinued Drugs | + | ||||
| 1 | Fabesetron | Drug Info | Discontinued in Phase 2 | Irritable bowel syndrome | [31] | |
| 2 | Naronapride | Drug Info | Discontinued in Phase 2 | Gastroesophageal reflux disease | [32] | |
| 3 | Norcisapride | Drug Info | Discontinued in Phase 2 | Gastroesophageal reflux disease | [33] | |
| 4 | SL65.0155 | Drug Info | Discontinued in Phase 2 | Parkinson disease | [34], [35] | |
| 5 | DAU-6285 | Drug Info | Terminated | Vomiting | [39], [40] | |
| 6 | LY-353433 | Drug Info | Terminated | Inflammatory bowel disease | [41] | |
| 7 | SK-951 | Drug Info | Terminated | Gastrointestinal disease | [42] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Agonist | [+] 24 Agonist drugs | + | ||||
| 1 | Cisapride | Drug Info | [1], [43] | |||
| 2 | HTF 919 | Drug Info | [44] | |||
| 3 | R0-93877 | Drug Info | [45] | |||
| 4 | Tegaserod | Drug Info | [8] | |||
| 5 | Mosapride | Drug Info | [46] | |||
| 6 | DSP-6952 | Drug Info | [48] | |||
| 7 | PF-885706 | Drug Info | [49] | |||
| 8 | SPD-557 | Drug Info | [51] | |||
| 9 | TD-5108 | Drug Info | [43], [46] | |||
| 10 | YKP-GI | Drug Info | [53] | |||
| 11 | DA-6886 | Drug Info | [51] | |||
| 12 | M-0004 | Drug Info | [51] | |||
| 13 | PF-04995274 | Drug Info | [54] | |||
| 14 | SUVN-D4010 | Drug Info | [28], [29] | |||
| 15 | Naronapride | Drug Info | [57] | |||
| 16 | SL65.0155 | Drug Info | [59] | |||
| 17 | SK-951 | Drug Info | [62] | |||
| 18 | alpha-methyl-5-HT | Drug Info | [66] | |||
| 19 | ER-21018 | Drug Info | [51] | |||
| 20 | RQ-00000010 | Drug Info | [51] | |||
| 21 | RS 57639 | Drug Info | [66] | |||
| 22 | RS 67333 | Drug Info | [76] | |||
| 23 | RS67506 | Drug Info | [77] | |||
| 24 | SUVN-1004028 | Drug Info | [51] | |||
| Modulator | [+] 13 Modulator drugs | + | ||||
| 1 | Renzapride | Drug Info | [47] | |||
| 2 | Lintopride | Drug Info | [12] | |||
| 3 | PRX-3140 | Drug Info | [50] | |||
| 4 | TD-8954 | Drug Info | [52] | |||
| 5 | BIMU-1 | Drug Info | [23] | |||
| 6 | Fabesetron | Drug Info | [56] | |||
| 7 | DAU-6285 | Drug Info | [60] | |||
| 8 | (R)-zacopride | Drug Info | [63] | |||
| 9 | MDDR 287569 | Drug Info | [4], [70] | |||
| 10 | ML-10302 | Drug Info | [72] | |||
| 11 | SC-52491 | Drug Info | [79] | |||
| 12 | SC-54750 | Drug Info | [79] | |||
| 13 | VRX-03011 | Drug Info | [80] | |||
| Antagonist | [+] 14 Antagonist drugs | + | ||||
| 1 | SB-207266A | Drug Info | [45] | |||
| 2 | SER-101 | Drug Info | [55] | |||
| 3 | LY-353433 | Drug Info | [61] | |||
| 4 | SB 203186 | Drug Info | [44] | |||
| 5 | AF-3473 | Drug Info | [51] | |||
| 6 | GR 125487 | Drug Info | [68] | |||
| 7 | ML 10375 | Drug Info | [71] | |||
| 8 | R-116712 | Drug Info | [73] | |||
| 9 | RO 116 1148 | Drug Info | [74] | |||
| 10 | RS 100235 | Drug Info | [75] | |||
| 11 | RS 116 0086 | Drug Info | [74] | |||
| 12 | SB 204070 | Drug Info | [66] | |||
| 13 | [11C]SB207145 | Drug Info | [81] | |||
| 14 | [123I]SB 207710 | Drug Info | [51] | |||
| Inhibitor | [+] 7 Inhibitor drugs | + | ||||
| 1 | Norcisapride | Drug Info | [58] | |||
| 2 | 1-((S)-2-aminopropyl)-1H-indazol-6-ol | Drug Info | [64] | |||
| 3 | 4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one | Drug Info | [65] | |||
| 4 | BARETTIN | Drug Info | [67] | |||
| 5 | GR-113808 | Drug Info | [69] | |||
| 6 | SB-207710 | Drug Info | [78] | |||
| 7 | SEROTONIN | Drug Info | [67] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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 Tissue Distribution
Human Pathway Affiliation
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Calcium signaling pathway | hsa04020 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| cAMP signaling pathway | hsa04024 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Serotonergic synapse | hsa04726 | Affiliated Target |
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| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "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 Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Calcium signaling pathway | |||||
| 2 | cAMP signaling pathway | |||||
| 3 | Neuroactive ligand-receptor interaction | |||||
| 4 | Serotonergic synapse | |||||
| Panther Pathway | [+] 2 Panther Pathways | + | ||||
| 1 | Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway | |||||
| 2 | 5HT4 type receptor mediated signaling pathway | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Excitatory Neural Signalling Through 5-HTR 4 and Serotonin | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Serotonin receptors | |||||
| 2 | G alpha (s) signalling events | |||||
| WikiPathways | [+] 5 WikiPathways | + | ||||
| 1 | Serotonin Receptor 4/6/7 and NR3C Signaling | |||||
| 2 | Monoamine GPCRs | |||||
| 3 | GPCRs, Class A Rhodopsin-like | |||||
| 4 | GPCR ligand binding | |||||
| 5 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Metoclopramide stimulates catecholamine- and granin-derived peptide secretion from pheochromocytoma cells through activation of serotonin type 4 (5... Endocr Relat Cancer. 2009 Mar;16(1):281-90. | |||||
| 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: 240). | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020210. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006410) | |||||
| REF 6 | 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89. | |||||
| 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: 244). | |||||
| REF 8 | Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313. | |||||
| REF 9 | 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: 225). | |||||
| REF 10 | ClinicalTrials.gov (NCT00421746) A Clinical Study Assessing the Potential of Piboserod for the Treatment of Heart Failure. U.S. National Institutes of Health. | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034751) | |||||
| REF 12 | The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility. Aliment Pharmacol Ther. 1995 Oct;9(5):563-9. | |||||
| REF 13 | ClinicalTrials.gov (NCT00730665) Efficacy And Safety Of PF-00885706 For The Relief Of Symptoms In Subjects With Gastro-esophageal Reflux Disease (GERD). U.S. National Institutes of Health. | |||||
| 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 800021864) | |||||
| REF 15 | Clinical pipeline report, company report or official report of Department of Pharmacology University of Wisconsin School of Medicine. | |||||
| REF 16 | ClinicalTrials.gov (NCT01370863) An Explorative Trial to Evaluate the Pharmacodynamic Effect of SPD557 on Reflux Parameters in Refractory GERD Patients. U.S. National Institutes of Health. | |||||
| 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: 8425). | |||||
| REF 18 | ClinicalTrials.gov (NCT00391820) Evaluate the Safety and Efficacy of a 5-HT4 Agonist in Chronic Constipation (ACCORD Trial). U.S. National Institutes of Health. | |||||
| REF 19 | ClinicalTrials.gov (NCT03827655) A Study of TAK-954 to Treat Gastrointestinal Dysfunction in Adults After Surgery. U.S. National Institutes of Health. | |||||
| REF 20 | 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: 8427). | |||||
| REF 21 | ClinicalTrials.gov (NCT01989234) A Multicenter, Double-Blind, Randomized, Placebo-Controlled, 12-Week, Dose-Range-Finding Trial of YKP10811 Capsules Administered Once Daily to Subjects With Chronic Idiopathic Constipation. U.S. National Institutes of Health. | |||||
| REF 22 | 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: 234). | |||||
| REF 23 | Gastroprokinetic properties of the benzimidazolone derivative BIMU 1, an agonist at 5-hydroxytryptamine4 and antagonist at 5-hydroxytryptamine3 receptors. Naunyn Schmiedebergs Arch Pharmacol. 1994 Apr;349(4):338-45. | |||||
| REF 24 | ClinicalTrials.gov (NCT01633723) Phase I Clinical Trial of DA-6886 in Healthy Male Subjects. U.S. National Institutes of Health. | |||||
| REF 25 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026666) | |||||
| REF 26 | ClinicalTrials.gov (NCT01193062) Study In Healthy Subjects To Evaluate The Changes In The Protein sAPP-Alpha In Cerebrospinal Fluid Following A Single Oral Dose Of PF-04995274. U.S. National Institutes of Health. | |||||
| REF 27 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033318) | |||||
| REF 28 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 29 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 30 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004004) | |||||
| REF 31 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001434) | |||||
| REF 32 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019926) | |||||
| REF 33 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007174) | |||||
| REF 34 | 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: 29). | |||||
| REF 35 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014352) | |||||
| REF 36 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021879) | |||||
| REF 37 | 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: 238). | |||||
| REF 38 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003270) | |||||
| REF 39 | 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: 246). | |||||
| REF 40 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002002) | |||||
| REF 41 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007508) | |||||
| REF 42 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011740) | |||||
| REF 43 | The in vivo gastrointestinal activity of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul;378(1):139-47. | |||||
| REF 44 | 5-Hydroxytryptamine mediated contractions in isolated preparations of equine ileum and pelvic flexure: pharmacological characterization of a new 5-HT(4) agonist. J Vet Pharmacol Ther. 2002 Feb;25(1):49-58. | |||||
| REF 45 | Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32. | |||||
| REF 46 | The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jul;378(1):125-37. | |||||
| REF 47 | Pharmacology and metabolism of renzapride : a novel therapeutic agent for the potential treatment of irritable bowel syndrome. Drugs R D. 2008;9(1):37-63. | |||||
| REF 48 | DSP-6952, a high affinity serotonin (5-HT4) receptor partial agonist. Sumitomo Dainippon Pharma Co. Ltd. | |||||
| REF 49 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025579) | |||||
| REF 50 | Clinical pipeline report, company report or official report of Nanotherapeutics. | |||||
| REF 51 | 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: 9). | |||||
| REF 52 | The Pharmacology of TD-8954, a Potent and Selective 5-HT(4) Receptor Agonist with Gastrointestinal Prokinetic Properties. Front Pharmacol. 2011 May 30;2:25. | |||||
| REF 53 | A randomized trial of 5-hydroxytryptamine4-receptor agonist, YKP10811, on colonic transit and bowel function in functional constipation. Clin Gastroenterol Hepatol. 2015 Apr;13(4):701-8.e1. | |||||
| REF 54 | Pharmacokinetics, safety and tolerability of PF04995274: A 5HT4 partial agonist being developed for the treatment of Alzheimer's disease. Alzheimer's and Dementia. | |||||
| REF 55 | Phase I clinical trail of SER101 (RO1160367) for treating heart failure leukemia. Roche. | |||||
| REF 56 | Pharmacological characterization of FK1052, a dihydropyridoindole derivative, as a new serotonin 3 and 4 dual receptor antagonist. J Pharmacol Exp Ther. 1993 May;265(2):752-8. | |||||
| REF 57 | Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012 Apr;35(7):745-67. | |||||
| REF 58 | mu-Opioid/5-HT4 dual pharmacologically active agents-efforts towards an effective opioid analgesic with less GI and respiratory side effects (Part I). Bioorg Med Chem Lett. 2009 Oct 1;19(19):5679-83. | |||||
| REF 59 | SL65.0155, a novel 5-hydroxytryptamine(4) receptor partial agonist with potent cognition-enhancing properties. J Pharmacol Exp Ther. 2002 Aug;302(2):731-41. | |||||
| REF 60 | The novel 5-HT4 receptor antagonist DAU 6285 antagonizes 5-hydroxytryptamine-induced tachycardia in pigs. Eur J Pharmacol. 1993 Mar 23;233(2-3):295-7. | |||||
| REF 61 | LY353433, a potent, orally effective, long-acting 5-HT(4) receptor antagonist: comparison to cisapride and RS23597-190. J Pharmacol Exp Ther. 1996 Apr;277(1):97-104. | |||||
| REF 62 | Identification of SK-951, a novel benzofuran derivative, as an agonist to 5-HT4 receptors. Jpn J Pharmacol. 1999 Feb;79(2):203-12. | |||||
| REF 63 | R-zacopride, a 5-HT3 antagonist/5-HT4 agonist, reduces sleep apneas in rats. Pharmacol Biochem Behav. 2001 May-Jun;69(1-2):283-9. | |||||
| REF 64 | 1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. J Med Chem. 2006 Jan 12;49(1):318-28. | |||||
| REF 65 | 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 66 | [3H]RS 57639, a high affinity, selective 5-HT4 receptor partial agonist, specifically labels guinea-pig striatal and rat cloned (5-HT4S and 5-HT4L) receptors. Neuropharmacology. 1997 Apr-May;36(4-5):671-9. | |||||
| REF 67 | Brominated cyclodipeptides from the marine sponge Geodia barretti as selective 5-HT ligands. J Nat Prod. 2006 Oct;69(10):1421-4. | |||||
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