Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT953CX)

• DTT Name: Motilin receptor (MLNR)
• Synonyms: MLNR; Gprotein coupled receptor 38
• Gene Name: MLNR
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: MTLR_HUMAN
• TTD ID: T62306
• Sequence:
  MGSPWNGSDGPEGAREPPWPALPPCDERRCSPFPLGALVPVTAVCLCLFVVGVSGNVVTV
  MLIGRYRDMRTTTNLYLGSMAVSDLLILLGLPFDLYRLWRSRPWVFGPLLCRLSLYVGEG
  CTYATLLHMTALSVERYLAICRPLRARVLVTRRRVRALIAVLWAVALLSAGPFLFLVGVE
  QDPGISVVPGLNGTARIASSPLASSPPLWLSRAPPPSPPSGPETAEAAALFSRECRPSPA
  QLGALRVMLWVTTAYFFLPFLCLSILYGLIGRELWSSRRPLRGPAASGRERGHRQTVRVL
  LVVVLAFIICWLPFHVGRIIYINTEDSRMMYFSQYFNIVALQLFYLSASINPILYNLISK
  KYRAAAFKLLLARKSRPRGFHRSRDTAGEVAGDTGGDTVGYTETSANVKTMG
• Function: Receptor for motilin.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MOTILIN	DMVILAD	N. A.	N. A.	Phase 4	[1]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Camicinal	DMAKSMX	Delayed gastric emptying	DA41.00	Phase 2	[2]
Mitemcinal fumarate	DMOJ7QA	Pain	MG30-MG3Z	Phase 2	[3]
DS-3801	DM6WN9X	Constipation	DD91.1	Phase 1	[4]
GSK-1322888	DMNYGB8	Gastroparesis	DA41.00	Phase 1	[5]
KOS-2187	DM4953W	Gastroesophageal reflux disease	DA22.Z	Phase 1	[6]
RWJ-68023	DM4O07Q	Irritable bowel syndrome	DD91.0	Phase 1	[7]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KC-11458	DMOITN2	Gastric motility disorder	DA21	Discontinued in Phase 2	[8]
KW-5139	DMLOKXI	Pain	MG30-MG3Z	Discontinued in Phase 2	[9]
SLV-305	DMBZM0D	Gastric motility disorder	DA21	Discontinued in Phase 2	[2]
SLV-311	DM5TJIY	Gastrointestinal disease	DE2Z	Discontinued in Phase 1	[10]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK-326416	DMFJ0ZA	Gastroparesis	DA41.00	Preclinical	[11]
TZP-202	DMRGZQA	Dyspepsia	MD92	Preclinical	[12]

11 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CEM-301	DMQ0HCT	Gastric motility disorder	DA21	Investigative	[2]
EM-523	DMC4XJ6	Discovery agent	N.A.	Investigative	[13]
GM-109	DMMDU0K	Discovery agent	N.A.	Investigative	[14]
KOS1326	DMYDGA7	Discovery agent	N.A.	Investigative	[13]
MA-2029	DMKWQ52	Discovery agent	N.A.	Investigative	[15]
ME36	DMOZAQ6	Discovery agent	N.A.	Investigative	[13]
ME4	DMO5E2L	Discovery agent	N.A.	Investigative	[13]
ME67	DM3C6X2	Discovery agent	N.A.	Investigative	[13]
RQ-00201894	DM4T8KV	Gastroesophageal reflux disease	DA22.Z	Investigative	[2]
TZP-201	DMD6CLG	Diarrhea	ME05.1	Investigative	[2]
[Leu13]motilin (human)	DMXTY6L	Discovery agent	N.A.	Investigative	[16]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Irritable bowel syndrome	DD91.0	Rectal colon tissue	6.35E-02	-0.06	-0.27

References

• [1] Discovery of a new class of macrocyclic antagonists to the human motilin receptor. J Med Chem. 2006 Nov 30;49(24):7190-7.
• [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. (Target id: 297).
• [3] Clinical pipeline report, company report or official report of Roche (2009).
• [4] Clinical pipeline report, company report or official report of Daiichi Sankyo.
• [5] 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.
• [6] Kosan Announces Selection of KOS-2187 As Motilide Clinical Candidate at World Congress of Gastroenterology Meeting. Kosan. 2006.
• [7] Effects of a nonpeptide motilin receptor antagonist on proximal gastric motor function. Br J Clin Pharmacol. 2004 Apr;57(4):393-401.
• [8] Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis. Aliment Pharmacol Ther. 2004 Aug 1;20(3):333-8.
• [9] Stimulating action of KW-5139 (Leu13-motilin) on gastrointestinal motility in the rabbit. Br J Pharmacol. 1994 Jan;111(1):288-94.
• [10] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017412)
• [11] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [12] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800023009)
• [13] Desensitization of the human motilin receptor by motilides. J Pharmacol Exp Ther. 2005 Jun;313(3):1397-405.
• [14] 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.
• [15] 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.
• [16] Receptor for motilin identified in the human gastrointestinal system. Science. 1999 Jun 25;284(5423):2184-8.