Details of the Drug

General Information of Drug (ID: DMOJA5G)

Drug Name
Nuplazid
Synonyms
Pimavanserin tartrate; UNII-NA83F1SJSR; 706782-28-7; ACP 103; ACP-103; 706782-28-7 (tartrate); NA83F1SJSR; Pimavanserin tartrate [USAN]; Bis(1-(4-Fluorobenzyl)-1-(1-methylpiperidin-4-yl)-3-(4-(2-methylpropoxy)benzyl)urea) (2R,3R)-2,3-dihydroxybutanedioate; Pimavanserin tartrate (USAN); 1-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-(1-methylpiperidin-4-yl)urea, ((2R,3R)-2,3-dihydroxysuccinate) (2:1); Nuplazide (TN); pimavanserin hemitartrate; DTXSID50220958; CHEBI:133014; HMS3886L06; HY-14557A; Pimavanserin Dihydroxysuccinate(2:1); AKOS027327334; CCG-270608; CS-7954; 1-(4-fluorobenzyl)-3-(4-isobutoxybenzyl)-1-(1-methylpiperidin-4-yl)urea (2R,3R)-2,3-dihydroxysuccinate; AC-29901; AS-56699; N-(4-Fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1); Urea, N-((4-fluorophenyl)methyl)-N-(1-methyl-4-piperidinyl)-N'-((4-(2-methylpropoxy)phenyl)methyl)-, (2R,3R)-2,3-dihydroxybutanedioate (2:1); D08969; Q27284759; bis(4-{[(4-fluorophenyl)methyl]({[4-(2-methylpropoxy)phenyl]methyl}carbamoyl)amino}-1-methylpiperidin-1-ium) (2R,3R)-2,3-dihydroxybutanedioate; bis{N-[(4-fluorophenyl)methyl]-N-(1-methylpiperidin-4-yl)-N'-{[4-(2-methylpropoxy)phenyl]methyl}urea} (2R,3R)-2,3-dihydroxybutanedioate
Indication
Disease Entry ICD 11 Status REF
Alzheimer disease 8A20 Phase 2 [1]
Drug Type
Small molecular drug
Structure
3D MOL is unavailable 2D MOL
#Ro5 Violations (Lipinski):
4		 Molecular Weight 1005.2
Topological Polar Surface Area Not Available
Rotatable Bond Count 19
Hydrogen Bond Donor Count 6
Hydrogen Bond Acceptor Count 14
Chemical Identifiers
Formula
C54H74F2N6O10
IUPAC Name
(2R,3R)-2,3-dihydroxybutanedioic acid;1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)-3-[[4-(2-methylpropoxy)phenyl]methyl]urea
Canonical SMILES
CC(C)COC1=CC=C(C=C1)CNC(=O)N(CC2=CC=C(C=C2)F)C3CCN(CC3)C.CC(C)COC1=CC=C(C=C1)CNC(=O)N(CC2=CC=C(C=C2)F)C3CCN(CC3)C.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O
InChI
InChI=1S/2C25H34FN3O2.C4H6O6/c2*1-19(2)18-31-24-10-6-20(7-11-24)16-27-25(30)29(23-12-14-28(3)15-13-23)17-21-4-8-22(26)9-5-21;5-1(3(7)8)2(6)4(9)10/h2*4-11,19,23H,12-18H2,1-3H3,(H,27,30);1-2,5-6H,(H,7,8)(H,9,10)/t;;1-,2-/m..1/s1
InChIKey
RGSULKHNAKTFIZ-CEAXSRTFSA-N
Cross-matching ID
PubChem CID
11672491
ChEBI ID
CHEBI:133014
CAS Number
706782-28-7
TTD ID
DDI6B0

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
5-HT 2A receptor (HTR2A) TTJQOD7 5HT2A_HUMAN Agonist [2]
5-HT 2C receptor (HTR2C) TTWJBZ5 5HT2C_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 2C receptor (HTR2C) DTT HTR2C 1.02E-02 -0.45 -0.37
5-HT 2C receptor (HTR2C) DTT HTR2C 2.27E-01 0.27 0.6
5-HT 2A receptor (HTR2A) DTT HTR2A 1.68E-01 -0.3 -0.14
5-HT 2A receptor (HTR2A) DTT HTR2A 5.59E-01 0.15 0.21
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT02035553) A Study of the Safety and Efficacy of Pimavanserin in Patients With Alzheimer's Disease Psychosis. U.S. National Institutes of Health.
2 The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation and a novel therapeutic drug. Psychopharmacology (Berl). 2018 Nov;235(11):3083-3091.
3 Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
4 Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
5 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
6 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
7 Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
8 Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. Eur J Pharmacol. 2001 May 18;420(1):33-43.
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
10 Beneficial effects of sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, supplemented with pioglitazone on diabetic model mice. Endocr Res. 2009;34(1-2):18-30.
11 Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day.Schizophr Res.2012 Nov;141(2-3):144-52.
12 Clinical pipeline report, company report or official report of Lundbeck.
13 Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
14 The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes. Anesth Analg. 2004 May;98(5):1401-6, table of contents.
15 Inverse agonist and neutral antagonist actions of antidepressants at recombinant and native 5-hydroxytryptamine2C receptors: differential modulatio... Mol Pharmacol. 2008 Mar;73(3):748-57.
16 Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60.
17 Spinal serotonin receptor activation modulates the exercise ventilatory response with increased dead space in goats. Respir Physiol Neurobiol. 2008 May 31;161(3):230-8.
18 Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
19 Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists ... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12.
20 SR46349-B, a 5-HT(2A/2C) receptor antagonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Neuropsychopharmacology. 2002 Sep;27(3):430-41.
21 Prediction of Efficacy of Vabicaserin, a 5-HT2C Agonist, for the Treatment of Schizophrenia Using a Quantitative Systems Pharmacology Model.CPT Pharmacometrics Syst Pharmacol.2014 Apr 23;3:e111.