Natural Product (NP) Details

General Information of the NP (ID: NP4023)
Name
Citicoline
Synonyms
citicoline; cytidine 5'-diphosphocholine; CDP-choline; citicholine; 987-78-0; Citidoline; Cytidoline; Difosfocin; Cyscholin; Haocolin; Nicholin; Niticolin; Recofnan; Recognan; Somazina; Suncholin; Colite; Ensign; cytidine diphosphate choline; Cytidine diphosphocholine; Citicolinum; Citicolina; Cytidine diphosphorylcholine; Choline cytidine diphosphate; Cytidine choline diphosphate; Cytidine 5'-(choline diphosphate); CDP-colina; Cytidine 5'-(cholinyl pyrophosphate); Choline 5'-cytidine diphosphate; cyticholine; Cytidine 5'-diphosphoric choline; Cytidindiphosphocholin; Cereb; Cytidine 5'-diphosphate choline; Cytidine diphosphate choline ester; citidin difosfato de colina; Emicholin; Nicolin; Meibis; CDP-cholin; CDP-choline (neutral charge); Cytidinediphosphoric choline; UNII-536BQ2JVC7; Cytidine 5'-(trihydrogen diphosphate), P'-(2-(trimethylammonio)ethyl) ester, inner salt; IP 302; IP-302; Choline cytidine 5'-pyrophosphate ester; Choline, ester with cytidine 5'-pyrophosphate; CDP-cholin [German]; [2-CYTIDYLATE-O'-PHOSPHONYLOXYL]-ETHYL-TRIMETHYL-AMMONIUM; CDP-colina [Spanish]; Corenalin; Startonyl; Ubelin; Citicoline [INN:JAN]; CYTIDINE-5'-DIPHOSPHOCHOLINE; Citicolinum [INN-Latin]; Citicolina [INN-Spanish]; 536BQ2JVC7; CHEBI:16436; 2-(((((((2R,3S,4R,5R)-5-(4-Amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(hydroxy)phosphoryl)oxy)oxidophosphoryl)oxy)-N,N,N-trimethylethanaminium; Cytidindiphosphocholin [German]; Cytidine diphosphate cholin ester; C14H26N4O11P2; EINECS 213-580-7; Citidin difosfato de colina [Spanish]; Cytidine 5-diphosphocholine; NSC 122002; BRN 4170138; Citifar; Hornbest; Neucolis; Sintoclar; Somazine; Reagin; Rexort; Audes; Emicholine F; Cytidine, 5'-pyrophosphate, ester with choline; Cytidine 5'-(trihydrogen diphosphate), P'-[2-(trimethylammonio)ethyl] ester, inner salt; Nicholin (TN); Citicoline (JP17/INN); cytidine-5' diphosphocholine; SCHEMBL221081; AOB5033; Cytidine 5-diphosphate-trihydrogen; MFCD00868097; AKOS025312525; CCG-269597; DB04290; DB12153; Choline, hydroxide, 5'-ester with cytidine 5'-(trihydrogen pyrophosphate), inner salt; cytidine-5'-pyrophosphate-hydroxycholine; [[(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] 2-(trimethylazaniumyl)ethyl phosphate; Cytidine 5'-(trihydrogen diphosphate), mono(2-(trimethylammonio)ethyl) ester, hydroxide, inner salt; K771; P-hydroxide[2-(trimethylammonio)ethyl] ester; C00307; D00057; W-100063; Q28529682; 5'-O-[(S)-hydroxy({[2-(trimethylammonio)ethoxy]phosphinato}oxy)phosphoryl]cytidine; 5'-O-[hydroxy({[2-(trimethylammonio)ethoxy]phosphinato}oxy)phosphoryl]cytidine; {2-[({[(2R,3S,4R,5R)-5-(4-amino-2-oxo-1,2-dihydropyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl phosphonato)oxy]ethyl}trimethylazanium
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Species Origin Escherichia coli ...     Click to Show/Hide
Escherichia coli
SuperKingdom: Bacteria
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli
Disease Cerebral ischaemia [ICD-11: 8B1Z] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.989
 
MDCK Permeability
 -5.108
 
PAMPA
 +++
 
HIA
 - - -
 
Distribution
VDss
 -0.55
 
PPB
 16.6%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 +
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 - - -
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 - - -
HLM Stability
 - - -
 
Excretion
CLplasma
 1.716
 
T1/2
 1.769
Toxicity
DILI
 +++
 
Rat Oral Acute Toxicity
 +
 
FDAMDD
 +++
 
Respiratory
 +++
 
Human Hepatotoxicity
 - -
 
Ototoxicity
 - - -
 
Drug-induced Nephrotoxicity
 +++
 
Drug-induced Neurotoxicity
 ++
 
Hematotoxicity
 - - -
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C14H26N4O11P2
PubChem CID
13804
Canonical SMILES
C[N+](C)(C)CCOP(=O)([O-])OP(=O)(O)OCC1C(C(C(O1)N2C=CC(=NC2=O)N)O)O
InChI
1S/C14H26N4O11P2/c1-18(2,3)6-7-26-30(22,23)29-31(24,25)27-8-9-11(19)12(20)13(28-9)17-5-4-10(15)16-14(17)21/h4-5,9,11-13,19-20H,6-8H2,1-3H3,(H3-,15,16,21,22,23,24,25)/t9-,11-,12-,13-/m1/s1
InChIKey
RZZPDXZPRHQOCG-OJAKKHQRSA-N
CAS Number
CAS 987-78-0
ChEBI ID
CHEBI:16436
TTD Drug ID
D02CFP
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Hypothermia      Cerebral ischaemia     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Middle cerebral artery occlusion (MCAo) was performed for 2 hours on Sprague-Dawley (SD) rats using intraluminal thread insertion.
                    Experimental
                    Result(s)		 By suppressing apoptotic processes citicoline with hypothermia is more effective than either used alone in ameliorating cerebral damage after transient focal ischemia.
          Growth factor      Diminished ovarian reserve     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 Synergistic effects of a low-dose combination of the growth factor bFGF and citicoline after temporary experimental focal cerebral ischemia and furthermore support the effectiveness of a combination treatment regimen for the management of acute stroke.
          Mexidol      Ischemic stroke     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 In patients treated with neipilept or with the combination of citicoline with 2-ethyl-6-methyl-3-hydroxypyridine succinate, plasma phosphatidylcholine was significantly increased.
          Physiotherapy      Oral cavity carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Clinical Trial
                    Experimental
                    Result(s)		 Citicoline in combination to physiotherapy appears to be a promising agent to improve gross motor function in patients with cerebral palsy versus physiotherapy alone.
          Benfotiamine      Substance abuse     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Experimental
                    Result(s)		 Co-administration of benfotiamine and citicoline was more effective than either alone in improving memory.
References
Reference 1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Reference 2 Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats. J Clin Neurosci. 2010 Feb;17(2):227-31.
Reference 3 Synergistic effects of a combination of low-dose basic fibroblast growth factor and citicoline after temporary experimental focal ischemia. Stroke. 1999 Feb;30(2):427-31; discussion 431-2.
Reference 4 [The study of the membrane-protective potential of the combination of 2-ethyl-6-methyl-3-hydroxypyridine-succinate and citicoline]. Zh Nevrol Psikhiatr Im S S Korsakova. 2018;118(1):18-22.
Reference 5 Combination of citicoline and physiotherapy in children with cerebral palsy. Int J Prev Med. 2014 Oct;5(10):1308-13.
Reference 6 Protective Effects of Citicoline and Benfotiamine Each Alone and in Combination on Streptozotocin-induced Memory Impairment in Mice. Clin Psychopharmacol Neurosci. 2020 Feb 29;18(1):81-92.
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