Details of the Drug

General Information of Drug (ID: DMZ8QRI)

Drug Name
PF-04995274
Synonyms
UNII-XI179PG9LV; PF 04995274; XI179PG9LV; 1331782-27-4; CHEMBL2152922; (R)-4-((4-(((4-(Tetrahydrofuran-3-yloxy)-1,2-benzisoxazol-3-yl)oxy)methyl)piperidin-1-yl)methyl)tetrahydro-2H-pyran-4-ol; PF04995274; compound 2d [PMID: 22974325]; SCHEMBL619629; GTPL9059; WLLOFQROROXOMO-GOSISDBHSA-N; ZINC95577747; BDBM50398598; DB12675; NCGC00386746-01; PF-04995274, > 4-[[4-[[4-[(3R)-oxolan-3-yl]oxy-1,2-benzoxazol-3-yl]oxymethyl]piperidin-1-yl]methyl]oxan-4-ol
Indication
Disease Entry ICD 11 Status REF
Alzheimer disease 8A20 Phase 1 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 432.5
Topological Polar Surface Area (xlogp) 2.4
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C23H32N2O6
IUPAC Name
4-[[4-[[4-[(3R)-oxolan-3-yl]oxy-1,2-benzoxazol-3-yl]oxymethyl]piperidin-1-yl]methyl]oxan-4-ol
Canonical SMILES
C1COC[C@@H]1OC2=CC=CC3=C2C(=NO3)OCC4CCN(CC4)CC5(CCOCC5)O
InChI
InChI=1S/C23H32N2O6/c26-23(7-12-27-13-8-23)16-25-9-4-17(5-10-25)14-29-22-21-19(30-18-6-11-28-15-18)2-1-3-20(21)31-24-22/h1-3,17-18,26H,4-16H2/t18-/m1/s1
InChIKey
WLLOFQROROXOMO-GOSISDBHSA-N
Cross-matching ID
PubChem CID
53354764
CAS Number
1331782-27-4
DrugBank ID
DB12675
TTD ID
D02YKI

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
5-HT 4 receptor (HTR4) TT07C3Y 5HT4R_HUMAN Agonist [2]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Alzheimer disease
ICD Disease Classification 8A20
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
5-HT 4 receptor (HTR4) DTT HTR4 6.16E-01 -0.03 -0.24
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 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.
2 Pharmacokinetics, safety and tolerability of PF04995274: A 5HT4 partial agonist being developed for the treatment of Alzheimer's disease. Alzheimer's and Dementia.
3 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.
4 Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
5 Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
6 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.
7 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.
8 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.
9 The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility. Aliment Pharmacol Ther. 1995 Oct;9(5):563-9.
10 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.
11 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.