Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T62306
(Former ID: TTDC00155)
|
|||||
| Target Name |
Motilin receptor (MLNR)
|
|||||
| Synonyms |
MLNR; Gprotein coupled receptor 38
Click to Show/Hide
|
|||||
| Gene Name |
MLNR
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 5 Target-related Diseases | + | ||||
| 1 | Gastroduodenal motor/secretory disorder [ICD-11: DA41] | |||||
| 2 | Pain [ICD-11: MG30-MG3Z] | |||||
| 3 | Digestive system disease [ICD-11: DE2Z] | |||||
| 4 | Gastro-oesophageal reflux disease [ICD-11: DA22] | |||||
| 5 | Irritable bowel syndrome [ICD-11: DD91] | |||||
| Function |
Receptor for motilin.
Click to Show/Hide
|
|||||
| BioChemical Class |
GPCR rhodopsin
|
|||||
| UniProt ID | ||||||
| Sequence |
MGSPWNGSDGPEGAREPPWPALPPCDERRCSPFPLGALVPVTAVCLCLFVVGVSGNVVTV
MLIGRYRDMRTTTNLYLGSMAVSDLLILLGLPFDLYRLWRSRPWVFGPLLCRLSLYVGEG CTYATLLHMTALSVERYLAICRPLRARVLVTRRRVRALIAVLWAVALLSAGPFLFLVGVE QDPGISVVPGLNGTARIASSPLASSPPLWLSRAPPPSPPSGPETAEAAALFSRECRPSPA QLGALRVMLWVTTAYFFLPFLCLSILYGLIGRELWSSRRPLRGPAASGRERGHRQTVRVL LVVVLAFIICWLPFHVGRIIYINTEDSRMMYFSQYFNIVALQLFYLSASINPILYNLISK KYRAAAFKLLLARKSRPRGFHRSRDTAGEVAGDTGGDTVGYTETSANVKTMG Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 6 Clinical Trial Drugs | + | ||||
| 1 | Camicinal | Drug Info | Phase 2 | Delayed gastric emptying | [2], [3] | |
| 2 | Mitemcinal fumarate | Drug Info | Phase 2 | Pain | [4] | |
| 3 | DS-3801 | Drug Info | Phase 1 | Constipation | [5] | |
| 4 | GSK-1322888 | Drug Info | Phase 1 | Gastroparesis | [6] | |
| 5 | KOS-2187 | Drug Info | Phase 1 | Gastroesophageal reflux disease | [7] | |
| 6 | RWJ-68023 | Drug Info | Phase 1 | Irritable bowel syndrome | [8] | |
| Discontinued Drug(s) | [+] 4 Discontinued Drugs | + | ||||
| 1 | KC-11458 | Drug Info | Discontinued in Phase 2 | Gastric motility disorder | [9] | |
| 2 | KW-5139 | Drug Info | Discontinued in Phase 2 | Pain | [10] | |
| 3 | SLV-305 | Drug Info | Discontinued in Phase 2 | Gastric motility disorder | [11] | |
| 4 | SLV-311 | Drug Info | Discontinued in Phase 1 | Gastrointestinal disease | [12] | |
| Preclinical Drug(s) | [+] 2 Preclinical Drugs | + | ||||
| 1 | GSK-326416 | Drug Info | Preclinical | Gastroparesis | [7] | |
| 2 | TZP-202 | Drug Info | Preclinical | Dyspepsia | [13] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | MOTILIN | Drug Info | [1] | |||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | Camicinal | Drug Info | [14] | |||
| 2 | KC-11458 | Drug Info | [19] | |||
| 3 | KW-5139 | Drug Info | [20] | |||
| 4 | SLV-305 | Drug Info | [14] | |||
| 5 | SLV-311 | Drug Info | [21] | |||
| Agonist | [+] 13 Agonist drugs | + | ||||
| 1 | Mitemcinal fumarate | Drug Info | [15] | |||
| 2 | DS-3801 | Drug Info | [16] | |||
| 3 | GSK-1322888 | Drug Info | [6] | |||
| 4 | KOS-2187 | Drug Info | [17] | |||
| 5 | GSK-326416 | Drug Info | [7] | |||
| 6 | CEM-301 | Drug Info | [14] | |||
| 7 | EM-523 | Drug Info | [23] | |||
| 8 | KOS1326 | Drug Info | [23] | |||
| 9 | ME36 | Drug Info | [23] | |||
| 10 | ME4 | Drug Info | [23] | |||
| 11 | ME67 | Drug Info | [23] | |||
| 12 | RQ-00201894 | Drug Info | [14] | |||
| 13 | [Leu13]motilin (human) | Drug Info | [26] | |||
| Antagonist | [+] 5 Antagonist drugs | + | ||||
| 1 | RWJ-68023 | Drug Info | [18] | |||
| 2 | TZP-202 | Drug Info | [22] | |||
| 3 | GM-109 | Drug Info | [24] | |||
| 4 | MA-2029 | Drug Info | [25] | |||
| 5 | TZP-201 | Drug Info | [14] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| 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).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
|
|
| 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 | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 1.07E-04 | Radiality | 3.98E-03 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.00E+00 | Topological coefficient | . | Eccentricity | 1 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| 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 Profiles in Patients | Top | |||||
|---|---|---|---|---|---|---|
| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
|---|---|---|---|---|---|---|
| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Peptide ligand-binding receptors | |||||
| 2 | G alpha (q) signalling events | |||||
| WikiPathways | [+] 4 WikiPathways | + | ||||
| 1 | GPCRs, Class A Rhodopsin-like | |||||
| 2 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 3 | GPCR ligand binding | |||||
| 4 | GPCR downstream signaling | |||||
| Target-Related Models and Studies | Top | |||||
|---|---|---|---|---|---|---|
| Target Validation | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Discovery of a new class of macrocyclic antagonists to the human motilin receptor. J Med Chem. 2006 Nov 30;49(24):7190-7. | |||||
| 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: 4035). | |||||
| REF 3 | ClinicalTrials.gov (NCT02210000) A Study to Evaluate the Effect of Camicinal on Gastroparesis Symptoms in Type 1 and 2 Diabetic Subjects With Gastroparesis. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT00050882) Safety and Effectiveness of an Investigational Agent (GM-611) in Patients With Diabetic Gastroparesis. U.S. National Institutes of Health. | |||||
| 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 800040749) | |||||
| REF 6 | ClinicalTrials.gov (NCT01294566) FTIH to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses of GSK1322888 in Healthy Caucasian and Japanese Volunteers. U.S. National Institutes of Health. | |||||
| REF 7 | Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26. | |||||
| REF 8 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021456) | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008138) | |||||
| REF 10 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002731) | |||||
| 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 800014470) | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017412) | |||||
| 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 800023009) | |||||
| REF 14 | 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: 297). | |||||
| REF 15 | Clinical pipeline report, company report or official report of Roche (2009). | |||||
| REF 16 | Clinical pipeline report, company report or official report of Daiichi Sankyo. | |||||
| REF 17 | Kosan Announces Selection of KOS-2187 As Motilide Clinical Candidate at World Congress of Gastroenterology Meeting. Kosan. 2006. | |||||
| REF 18 | Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function. Br J Clin Pharmacol. 2004 Apr;57(4):393-401. | |||||
| REF 19 | Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis. Aliment Pharmacol Ther. 2004 Aug 1;20(3):333-8. | |||||
| REF 20 | Stimulating action of KW-5139 (Leu13-motilin) on gastrointestinal motility in the rabbit. Br J Pharmacol. 1994 Jan;111(1):288-94. | |||||
| REF 21 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017412) | |||||
| REF 22 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023009) | |||||
| REF 23 | Desensitization of the human motilin receptor by motilides. J Pharmacol Exp Ther. 2005 Jun;313(3):1397-405. | |||||
| REF 24 | Design and synthesis of motilin antagonists derived from the [1-4] fragment of porcine motilin. J Med Chem. 2002 Jan 31;45(3):670-5. | |||||
| REF 25 | Oral administration of MA-2029, a novel selective and competitive motilin receptor antagonist, inhibits motilin-induced intestinal contractions and visceral pain in rabbits. Eur J Pharmacol. 2008 Mar10;581(3):296-305. | |||||
| REF 26 | Receptor for motilin identified in the human gastrointestinal system. Science. 1999 Jun 25;284(5423):2184-8. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.