Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4FJ0K3)

DOT Name	Cholinephosphotransferase 1 (CHPT1)
Synonyms	hCPT1; EC 2.7.8.2; AAPT1-like protein; Diacylglycerol cholinephosphotransferase 1
Gene Name	CHPT1
Related Disease	Gastrointestinal mucositis ( ) Glioblastoma multiforme ( ) Liver cirrhosis ( ) Psoriatic arthritis ( ) Triple negative breast cancer ( ) Advanced cancer ( ) Breast neoplasm ( ) Carcinoma ( ) Carnitine palmitoyltransferase II deficiency ( ) Cataract ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Colorectal neoplasm ( ) Dilated cardiomyopathy 1A ( ) Epithelial ovarian cancer ( ) Fatty liver disease ( ) Hypoglycemia ( ) Lung adenocarcinoma ( ) Lung carcinoma ( ) Metabolic disorder ( ) Mitochondrial trifunctional protein deficiency ( ) Neuroblastoma ( ) Non-alcoholic fatty liver disease ( ) Non-insulin dependent diabetes ( ) Non-small-cell lung cancer ( ) Obesity ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Prostate cancer ( ) Rectal carcinoma ( ) Renal cell carcinoma ( ) Schizophrenia ( ) Small-cell lung cancer ( ) Tourette syndrome ( ) Type-1/2 diabetes ( ) Acute myelogenous leukaemia ( ) Breast cancer ( ) Hepatocellular carcinoma ( ) Leukopenia ( ) Medulloblastoma ( ) Hyperlipidemia ( ) Lung cancer ( ) Adenocarcinoma ( ) Attention deficit hyperactivity disorder ( ) Breast carcinoma ( ) Pancreatic cancer ( ) Prostate carcinoma ( ) Psychotic disorder ( )
UniProt ID	CHPT1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.7.8.2
Pfam ID	PF01066
Sequence	MAAGAGAGSAPRWLRALSEPLSAAQLRRLEEHRYSAAGVSLLEPPLQLYWTWLLQWIPLW MAPNSITLLGLAVNVVTTLVLISYCPTATEEAPYWTYLLCALGLFIYQSLDAIDGKQARR TNSCSPLGELFDHGCDSLSTVFMAVGASIAARLGTYPDWFFFCSFIGMFVFYCAHWQTYV SGMLRFGKVDVTEIQIALVIVFVLSAFGGATMWDYTIPILEIKLKILPVLGFLGGVIFSC SNYFHVILHGGVGKNGSTIAGTSVLSPGLHIGLIIILAIMIYKKSATDVFEKHPCLYILM FGCVFAKVSQKLVVAHMTKSELYLQDTVFLGPGLLFLDQYFNNFIDEYVVLWMAMVISSF DMVIYFSALCLQISRHLHLNIFKTACHQAPEQVQVLSSKSHQNNMD
Function	Catalyzes the final step of de novo phosphatidylcholine (PC) synthesis, i.e. the transfer of choline phosphate from CDP-choline to the free hydroxyl of a diacylglycerol (DAG), producing a PC. It thereby plays a central role in the formation and maintenance of vesicular membranes.
Tissue Specificity	Highly expressed in testis, colon, small intestine, heart, prostate and spleen. Also detected in kidney, skeletal muscle, pancreas, leukocytes, ovary and thymus. Weakly expressed in the brain, placenta and lung. Overexpressed in cancerous breast epithelial cell lines.
KEGG Pathway	Phospho.te and phosphi.te metabolism (hsa00440 ) Glycerophospholipid metabolism (hsa00564 ) Ether lipid metabolism (hsa00565 ) Metabolic pathways (hsa01100 ) Choline metabolism in cancer (hsa05231 )
Reactome Pathway	Synthesis of PC (R-HSA-1483191 )

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Gastrointestinal mucositis	DIS140OB	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[2]
Liver cirrhosis	DIS4G1GX	Definitive	Biomarker	[3]
Psoriatic arthritis	DISLWTG2	Definitive	Biomarker	[4]
Triple negative breast cancer	DISAMG6N	Definitive	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Carcinoma	DISH9F1N	Strong	Biomarker	[8]
Carnitine palmitoyltransferase II deficiency	DIS3GFD9	Strong	Altered Expression	[9]
Cataract	DISUD7SL	Strong	Biomarker	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[14]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Altered Expression	[15]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[16]
Fatty liver disease	DIS485QZ	Strong	Altered Expression	[17]
Hypoglycemia	DISRCKR7	Strong	Biomarker	[18]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[19]
Lung carcinoma	DISTR26C	Strong	Biomarker	[20]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[21]
Mitochondrial trifunctional protein deficiency	DIS2MYYR	Strong	Altered Expression	[22]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[23]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[24]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[25]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[26]
Obesity	DIS47Y1K	Strong	Biomarker	[27]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[16]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[16]
Prostate cancer	DISF190Y	Strong	Biomarker	[28]
Rectal carcinoma	DIS8FRR7	Strong	Biomarker	[29]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[11]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[30]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[31]
Tourette syndrome	DISX9D54	Strong	Biomarker	[32]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[33]
Acute myelogenous leukaemia	DISCSPTN	moderate	Biomarker	[34]
Breast cancer	DIS7DPX1	moderate	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[35]
Leukopenia	DISJMBMM	moderate	Genetic Variation	[36]
Medulloblastoma	DISZD2ZL	moderate	Biomarker	[37]
Hyperlipidemia	DIS61J3S	Disputed	Biomarker	[33]
Lung cancer	DISCM4YA	Disputed	Biomarker	[38]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[39]
Attention deficit hyperactivity disorder	DISL8MX9	Limited	Biomarker	[40]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[5]
Pancreatic cancer	DISJC981	Limited	Biomarker	[41]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[28]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[42]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cholinephosphotransferase 1 (CHPT1).	[43]
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9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cholinephosphotransferase 1 (CHPT1).	[44]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cholinephosphotransferase 1 (CHPT1).	[45]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cholinephosphotransferase 1 (CHPT1).	[46]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cholinephosphotransferase 1 (CHPT1).	[47]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cholinephosphotransferase 1 (CHPT1).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cholinephosphotransferase 1 (CHPT1).	[49]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cholinephosphotransferase 1 (CHPT1).	[50]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Cholinephosphotransferase 1 (CHPT1).	[51]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cholinephosphotransferase 1 (CHPT1).	[52]
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⏷ Show the Full List of 9 Drug(s)

References

1	Preventative effects of selenium-enriched Bifidobacterium longum on irinotecan-induced small intestinal mucositis in mice.Benef Microbes. 2019 May 28;10(5):569-577. doi: 10.3920/BM2018.0096. Epub 2019 Apr 9.
2	Phase 2 Study of Radiation Therapy Plus Low-Dose Temozolomide Followed by Temozolomide and Irinotecan for Glioblastoma: NRG Oncology RTOG Trial 0420.Int J Radiat Oncol Biol Phys. 2019 Mar 15;103(4):878-886. doi: 10.1016/j.ijrobp.2018.11.008. Epub 2018 Nov 27.
3	Non-transplant therapies for patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B cirrhosis.Lancet Oncol. 2017 Feb;18(2):e101-e112. doi: 10.1016/S1470-2045(16)30569-1.
4	Vitamin D Ameliorates Fat Accumulation with AMPK/SIRT1 Activity in C2C12 Skeletal Muscle Cells.Nutrients. 2019 Nov 17;11(11):2806. doi: 10.3390/nu11112806.
5	Apatinib + CPT-11 + S-1 for treatment of refractory brain metastases in patient with triple-negative breast cancer: Case report and literature review.Medicine (Baltimore). 2018 Apr;97(15):e0349. doi: 10.1097/MD.0000000000010349.
6	Development and validation of a UHPLC-MS/MS method for the identification of irinotecan photodegradation products in water samples.Environ Pollut. 2020 Jan;256:113370. doi: 10.1016/j.envpol.2019.113370. Epub 2019 Oct 10.
7	Modulation of cholinephosphotransferase activity in breast cancer cell lines by Ro5-4864, a peripheral benzodiazepine receptor agonist.Biochem Biophys Res Commun. 2005 Jul 22;333(1):35-41. doi: 10.1016/j.bbrc.2005.05.071.
8	Carnitine palmitoyltransferase I in human carcinomas: a novel role in histone deacetylation?.Cancer Biol Ther. 2007 Oct;6(10):1606-13. doi: 10.4161/cbt.6.10.4742. Epub 2007 Jul 13.
9	Normal protein content but abnormally inhibited enzyme activity in muscle carnitine palmitoyltransferase II deficiency.J Neurol Sci. 2014 Apr 15;339(1-2):183-8. doi: 10.1016/j.jns.2014.02.011. Epub 2014 Feb 20.
10	Racial/ethnic differences in rates of complex cataract surgery among United States Medicare beneficiaries.J Cataract Refract Surg. 2018 Feb;44(2):140-143. doi: 10.1016/j.jcrs.2017.10.049. Epub 2018 Mar 7.
11	Impact of Perioperative Infection on Cancer Specific Survival after Nephrectomy for Renal Cell Carcinoma.J Urol. 2017 Nov;198(5):1027-1032. doi: 10.1016/j.juro.2017.05.070. Epub 2017 May 25.
12	Synergy between dihydromyricetin intervention and irinotecan chemotherapy delays the progression of colon cancer in mouse models.Food Funct. 2019 Apr 17;10(4):2040-2049. doi: 10.1039/c8fo01756e.
13	Protective effect of curcumin against irinotecaninduced intestinal mucosal injury via attenuation of NFB activation, oxidative stress and endoplasmic reticulum stress.Int J Oncol. 2019 Apr;54(4):1376-1386. doi: 10.3892/ijo.2019.4714. Epub 2019 Feb 11.
14	Survivin antagonizes chemotherapy-induced cell death of colorectal cancer cells.Oncotarget. 2018 Jun 12;9(45):27835-27850. doi: 10.18632/oncotarget.25600. eCollection 2018 Jun 12.
15	4-O-methylhonokiol protects against diabetic cardiomyopathy in type 2 diabetic mice by activation of AMPK-mediated cardiac lipid metabolism improvement.J Cell Mol Med. 2019 Aug;23(8):5771-5781. doi: 10.1111/jcmm.14493. Epub 2019 Jun 14.
16	The role of natural killer cells in combinatorial anti-cancer therapy using Sindbis viral vectors and irinotecan.Cancer Gene Ther. 2012 Aug;19(8):588-91. doi: 10.1038/cgt.2012.33. Epub 2012 Jun 8.
17	The adiponectin promoter activator NP-1 induces high levels of circulating TNF and weight loss in obese (fa/fa) Zucker rats.Sci Rep. 2018 Jun 29;8(1):9858. doi: 10.1038/s41598-018-27871-7.
18	Fatty acid oxidation disorders: outcome and long-term prognosis.J Inherit Metab Dis. 2010 Oct;33(5):501-6. doi: 10.1007/s10545-009-9001-1. Epub 2010 Jan 5.
19	Enhancement of CPT-11 antitumor activity by adenovirus-mediated expression of -glucuronidase in tumors.Cancer Gene Ther. 2011 Jun;18(6):381-9. doi: 10.1038/cgt.2011.3. Epub 2011 Feb 25.
20	Gefitinib enhances the antitumor activity of CPT-11 in vitro and in vivo by inhibiting ABCG2 but not ABCB1: a new clue to circumvent gastrointestinal toxicity risk.Chemotherapy. 2013;59(4):260-72. doi: 10.1159/000357772. Epub 2014 Jan 17.
21	Establishing a relationship between prolactin and altered fatty acid -oxidation via carnitine palmitoyl transferase 1 in breast cancer cells.BMC Cancer. 2011 Feb 4;11:56. doi: 10.1186/1471-2407-11-56.
22	Pharmacological inhibition of carnitine palmitoyltransferase 1 restores mitochondrial oxidative phosphorylation in human trifunctional protein deficient fibroblasts.Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1292-1299. doi: 10.1016/j.bbadis.2017.04.005. Epub 2017 Apr 6.
23	Enhanced Intratumoral Delivery of SN38 as a Tocopherol Oxyacetate Prodrug Using Nanoparticles in a Neuroblastoma Xenograft Model.Clin Cancer Res. 2018 Jun 1;24(11):2585-2593. doi: 10.1158/1078-0432.CCR-17-3811. Epub 2018 Mar 7.
24	Nonalcoholic fatty liver disease does not predict worse perioperative outcomes in bariatric surgery.Obes Res Clin Pract. 2019 Jul-Aug;13(4):416-418. doi: 10.1016/j.orcp.2019.06.006. Epub 2019 Jul 12.
25	Mitochondrial oxidative stress, endothelial function and metabolic control in patients with type II diabetes and periodontitis: A randomised controlled clinical trial.Int J Cardiol. 2018 Nov 15;271:263-268. doi: 10.1016/j.ijcard.2018.05.019. Epub 2018 Aug 1.
26	Synergistic antitumor activity of the SN-38-incorporating polymeric micelles NK012 with S-1 in a mouse model of non-small cell lung cancer.Int J Cancer. 2010 Dec 1;127(11):2699-706. doi: 10.1002/ijc.25282.
27	Lentivirus-mediated CTRP6 silencing ameliorates diet-induced obesity in mice.Exp Cell Res. 2018 Jun 1;367(1):15-23. doi: 10.1016/j.yexcr.2018.01.027. Epub 2018 Jan 31.
28	Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade.Oncotarget. 2017 Apr 21;8(34):56051-56065. doi: 10.18632/oncotarget.17359. eCollection 2017 Aug 22.
29	Operative Mortality Prediction for Primary Rectal Cancer: Age Matters.J Am Coll Surg. 2019 Apr;228(4):627-633. doi: 10.1016/j.jamcollsurg.2018.12.014. Epub 2019 Jan 8.
30	Neurophysiological Characterization of Attentional Performance Dysfunction in Schizophrenia Patients in a Reverse-Translated Task.Neuropsychopharmacology. 2017 May;42(6):1338-1348. doi: 10.1038/npp.2016.268. Epub 2016 Dec 5.
31	Banxia Xiexin Decoction Is Effective to Prevent and Control Irinotecan-Induced Delayed Diarrhea in Recurrent Small Cell Lung Cancer.Integr Cancer Ther. 2018 Dec;17(4):1109-1114. doi: 10.1177/1534735418801532. Epub 2018 Sep 19.
32	The 5 choice continuous performance test (5C-CPT): A novel tool to assess cognitive control across species.J Neurosci Methods. 2017 Dec 1;292:53-60. doi: 10.1016/j.jneumeth.2017.07.011. Epub 2017 Jul 25.
33	Lipid-associated metabolic signalling networks in pancreatic beta cell function.Diabetologia. 2020 Jan;63(1):10-20. doi: 10.1007/s00125-019-04976-w. Epub 2019 Aug 19.
34	In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
35	Synthesis of Dual Target CPT-Ala-Nor Conjugates and Their Biological Activity Evaluation.Anticancer Agents Med Chem. 2019;19(4):502-508. doi: 10.2174/1871520619666190121121933.
36	Prediction of irinotecan toxicity in metastatic colorectal cancer patients based on machine learning models with pharmacokinetic parameters.J Pharmacol Sci. 2019 May;140(1):20-25. doi: 10.1016/j.jphs.2019.03.004. Epub 2019 May 4.
37	Neural stem cell-mediated CE/CPT-11 enzyme/prodrug therapy in transgenic mouse model of intracerebellar medulloblastoma.Gene Ther. 2013 Feb;20(2):143-50. doi: 10.1038/gt.2012.12. Epub 2012 Mar 8.
38	Co-treatment with therapeutic neural stem cells expressing carboxyl esterase and CPT-11 inhibit growth of primary and metastatic lung cancers in mice.Oncotarget. 2014 Dec 30;5(24):12835-48. doi: 10.18632/oncotarget.2547.
39	Gene-specific damage produced by topoisomerase inhibitors in human lung cancer cells and peripheral mononuclear cells as assayed by polymerase chain reaction-stop assay.Anticancer Res. 1998 Sep-Oct;18(5A):3389-93.
40	Attention deficit hyperactivity disorder symptoms in patients with cystic fibrosis.J Cyst Fibros. 2018 Mar;17(2):281-285. doi: 10.1016/j.jcf.2017.11.020. Epub 2017 Dec 19.
41	Excipient-free nanodispersion of 7-ethyl-10-hydroxycamptothecin exerts potent therapeutic effects against pancreatic cancer cell lines and patient-derived xenografts.Cancer Lett. 2019 Nov 28;465:36-44. doi: 10.1016/j.canlet.2019.08.019. Epub 2019 Aug 31.
42	AKT1 moderation of cannabis-induced cognitive alterations in psychotic disorder.Neuropsychopharmacology. 2011 Nov;36(12):2529-37. doi: 10.1038/npp.2011.141. Epub 2011 Jul 20.
43	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
44	Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
45	Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
46	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
47	Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
48	Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
49	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
50	Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
51	Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
52	From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.