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

General Information of Drug (ID: DMI4XBM)

• Drug Name: Citicoline Drug Info
• Synonyms: Alphcolin; CerAxon; Citicholine; Hipercol; Neurex; Nicholin; Somazina; Trausan; Citicoline sodium; Cytidil diphosphocholine; CDP-choline; IP-302; Cytidine-5-diphosphocholine

Indication

Disease Entry	ICD 11	Status	REF
Cerebrovascular ischaemia	8B1Z	Approved	[1]

• Cross-matching ID:
  PubChem CID: 13804
  ChEBI ID: CHEBI:16436
  CAS Number: CAS 987-78-0
  TTD Drug ID: DMI4XBM
  INTEDE Drug ID: DR2077

Molecule-Related Drug Atlas

Drug(s) Affected By Poly polymerase 1 (PARP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[5]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[6]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[7]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[8]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[9]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[10]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[9]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[11]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]

Drug(s) Affected By Caspase-3 (CASP3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sevoflurane	DMC9O43	Anaesthesia	9A78.6	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[16]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[17]
Docetaxel	DMDI269	Advanced cancer	2A00-2F9Z	Approved	[18]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[19]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[20]
Mannitol	DMSCDY9	Bronchiectasis	CA24	Approved	[21]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[22]
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
ASM-like phosphodiesterase 3a (SMPDL3A)	DEQJ8N3	ASM3A_HUMAN	Substrate	[2]
CDP-choline phosphohydrolase (ADPRM)	DEH6S1Q	ADPRM_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[4]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Gene/Protein Processing	[4]

References

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• [2] The structure and catalytic mechanism of human sphingomyelin phosphodiesterase like 3a--an acid sphingomyelinase homologue with a novel nucleotide hydrolase activity. FEBS J. 2016 Mar;283(6):1107-23.
• [3] Molecular bases of catalysis and ADP-ribose preference of human Mn2+-dependent ADP-ribose/CDP-alcohol diphosphatase and conversion by mutagenesis to a preferential cyclic ADP-ribose phosphohydrolase. PLoS One. 2015 Feb 18;10(2):e0118680.
• [4] Citicoline increases glutathione redox ratio and reduces caspase-3 activation and cell death in staurosporine-treated SH-SY5Y human neuroblastoma cells. Brain Res. 2002 Dec 6;957(1):84-90. doi: 10.1016/s0006-8993(02)03605-3.
• [5] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [6] Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
• [7] Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
• [8] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [9] The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
• [10] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [11] Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
• [12] Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
• [13] Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.
• [14] Different apoptosis ratios and gene expressions in two human cell lines after sevoflurane anaesthesia. Acta Anaesthesiol Scand. 2009 Oct;53(9):1192-9. doi: 10.1111/j.1399-6576.2009.02036.x. Epub 2009 Jun 30.
• [15] [Mechanisms underlying the effect of arsenic trioxide on proliferation inhibition and apoptosis induction in myeloma cell line u266]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2007 Oct;15(5):982-5.
• [16] Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPAR-dependent pathway. Oncotarget. 2016 Mar 1;7(9):10345-62. doi: 10.18632/oncotarget.7213.
• [17] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [18] Comparison of burst of reactive oxygen species and activation of caspase-3 in apoptosis of K562 and HL-60 cells induced by docetaxel. Cancer Lett. 2004 Oct 8;214(1):103-13. doi: 10.1016/j.canlet.2004.03.047.
• [19] Induction of mitochondrial manganese superoxide dismutase confers resistance to apoptosis in acute myeloblastic leukaemia cells exposed to etoposide. Br J Haematol. 2000 Mar;108(3):574-81. doi: 10.1046/j.1365-2141.2000.01852.x.
• [20] Cisplatin-enhanced sensitivity of glioblastoma multiforme U251 cells to adenovirus-delivered TRAIL in vitro. Tumour Biol. 2010 Dec;31(6):613-22. doi: 10.1007/s13277-010-0077-x. Epub 2010 Jul 11.
• [21] Insulin-like growth factor I is the key growth factor in serum that protects neuroblastoma cells from hyperosmotic-induced apoptosis. J Cell Physiol. 2000 Jan;182(1):24-32. doi: 10.1002/(SICI)1097-4652(200001)182:1<24::AID-JCP3>3.0.CO;2-6.
• [22] mRNA expression analysis of a variety of apoptosis-related genes, including the novel gene of the BCL2-family, BCL2L12, in HL-60 leukemia cells after treatment with carboplatin and doxorubicin. Biol Chem. 2004 Nov;385(11):1099-103. doi: 10.1515/BC.2004.143.
• [23] Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-B axis: Shedding new light on resistance to Aprepitant. Int J Biochem Cell Biol. 2018 Oct;103:105-114. doi: 10.1016/j.biocel.2018.08.010. Epub 2018 Aug 23.