Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM5GY6Z)

• Drug Name: PH-709829 Drug Info
• Synonyms: PTGWFYYEAUFEAS-ZYHUDNBSSA-N; CHEMBL403858; PHA-709829; SCHEMBL844377; GTPL3997; BDBM50377050

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 10107234
  CAS Number: CAS 508202-22-0
  TTD Drug ID: DM5GY6Z

Molecule-Related Drug Atlas

Drug(s) Targeting Neuronal acetylcholine receptor alpha-7 (CHRNA7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ziprasidone	DMM58JY	Bipolar disorder	6A60	Approved	[3]
ALCURONIUM	DM2U4XQ	Anaesthesia	9A78.6	Approved	[4]
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[5]
CYTISINE	DMUF0BJ	Tobacco dependence	6C4A.2	Phase 3	[6]
EVP-6124	DMLQO7F	Alzheimer disease	8A20	Phase 3	[7]
GTS-21	DMEN5KA	Parkinson disease	8A00.0	Phase 2	[8]
JNJ-39393406	DMUOEKM	Depression	6A70-6A7Z	Phase 2	[9]
ABT-126	DM2OS51	Alzheimer disease	8A20	Phase 2	[10]
TC-6987	DMNFP21	Asthma	CA23	Phase 2	[11]
AQW-051	DMD2RFO	Alzheimer disease	8A20	Phase 2	[12]

Drug(s) Targeting 5-HT 3A receptor (HTR3A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dolasetron	DMMG26Z	Nausea	MD90	Approved	[13]
Alosetron	DML2A03	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[14]
Tropisetron	DMNSJ7V	Fibromyalgia	MG30.01	Approved	[15]
Palonosetron	DMBHMOX	Nausea	MD90	Approved	[16]
Levetiracetam	DMTGDN8	Epilepsy	8A60-8A68	Approved	[15]
Procaine	DM4LSNE	Anaesthesia	9A78.6	Approved	[17]
Cilansetron	DMP0NGX	Irritable bowel syndrome	DD91.0	Phase 3	[18]
BEMESETRON	DMSPJX9	N. A.	N. A.	Discontinued in Phase 3	[19]
Norcisapride	DMJSKUI	Gastroesophageal reflux disease	DA22.Z	Discontinued in Phase 2	[20]
YM-114	DML2IXO	Nausea	MD90	Discontinued in Phase 2	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Inhibitor	[2]
Neuronal acetylcholine receptor alpha-7 (CHRNA7)	TTLA931	ACHA7_HUMAN	Inhibitor	[2]

References

• [1] 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: 3997).
• [2] Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor:... Bioorg Med Chem Lett. 2008 Jun 15;18(12):3611-5.
• [3] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [4] Pharmacological characteristics and binding modes of caracurine V analogues and related compounds at the neuronal alpha7 nicotinic acetylcholine re... J Med Chem. 2007 Sep 20;50(19):4616-29.
• [5] Clinical pipeline report, company report or official report of Roche (2009).
• [6] 3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. Bioorg Med Chem Lett. 2005 Nov 15;15(22):4889-97.
• [7] Normalizing effects of EVP-6124, an alpha-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia. J Psychiatr Pract. 2014 Jan;20(1):12-24.
• [8] The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21). Behav Brain Res. 2000 Aug;113(1-2):169-81.
• [9] Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study. Neuropharmacology. 2013 Jan;64:197-204.
• [10] A phase 2 randomized, controlled trial of the alpha7 agonist ABT-126 in mild-to-moderate Alzheimer's dementia. Alzheimer's & Dementia: Translational Research & Clinical Interventions Volume 1, Issue 1, June 2015, Pages 81-90.
• [11] ClinicalTrials.gov (NCT01293669) Glycemic Control, Safety and Tolerability of TC-6987 Monotherapy in Type 2 Diabetes Mellitus. U.S. National Institutes of Health.
• [12] AQW051, a novel and selective nicotinic acetylcholine receptor alpha7 partial agonist, reduces l-Dopa-induced dyskinesias and extends the duration of l-Dopa effects in parkinsonian monkeys. Parkinsonism Relat Disord. 2014 Nov;20(11):1119-23.
• [13] Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, do... Lancet Oncol. 2009 Feb;10(2):115-24.
• [14] Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis. Am J Gastroenterol. 2009 Jul;104(7):1831-43; quiz 1844.
• [15] Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
• [16] Management of postoperative nausea and vomiting: focus on palonosetron. Ther Clin Risk Manag. 2009 Feb;5(1):21-34.
• [17] Local anesthetics have different mechanisms and sites of action at recombinant 5-HT3 receptors. Reg Anesth Pain Med. 2007 Nov-Dec;32(6):462-70.
• [18] Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea.Expert Opin Investig Drugs.2005 Feb;14(2):185-93.
• [19] Zatosetron, a potent, selective, and long-acting 5HT3 receptor antagonist: synthesis and structure-activity relationships. J Med Chem. 1992 Jan 24;35(2):310-9.
• [20] 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.
• [21] Effect of serotonin (5-HT)3-receptor antagonists YM060, YM114 (KAE-393), ondansetron and granisetron on 5-HT4 receptors and gastric emptying in rodents. Jpn J Pharmacol. 1995 Nov;69(3):205-14.