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

General Information of Drug (ID: DMGRZW2)

• Drug Name: Betaine Drug Info
• Synonyms: Cystadane

Indication

Disease Entry	ICD 11	Status	REF
Cystitis	GC00	Approved	[1]
Homocystinuria	5C50.B	Approved	[1]
Inborn error of metabolism	5C50-5C59	Approved	[2]

• Cross-matching ID:
  PubChem CID: 247
  ChEBI ID: CHEMBL17750
  CAS Number: CAS 107-43-7
  TTD Drug ID: DMGRZW2
  VARIDT Drug ID: DR00314

Molecule-Related Drug Atlas

Drug(s) Transported By Na(+)/Cl(-) betaine/GABA transporter (SLC6A12)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[6]
Glycine	DMIOZ29	Allergic rhinitis	CA08.0	Approved	[7]
L-Proline	DMKSTWR	Malnutrition	5B50-5B71	Approved	[7]
CHOLINE	DM5D9YK	Insomnia	7A00-7A0Z	Investigative	[7]

Drug(s) Affected By E3 ubiquitin-protein ligase MARCHF6 (MARCHF6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[8]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[5]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[9]
Diethylstilbestrol	DMN3UXQ	Gonorrheal vaginitis	GA02	Approved	[10]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[11]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[12]
Vorinostat	DMWMPD4	Adult acute monocytic leukemia		Approved	[13]
Tocopherol	DMBIJZ6	N. A.	N. A.	Phase 2	[8]
ANW-32821	DMMJOZD	N. A.	N. A.	Phase 2	[5]
CB-5083	DM12GN7	Multiple myeloma	2A83	Phase 1	[5]

Drug(s) Affected By Betaine--homocysteine S-methyltransferase 1 (BHMT)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[14]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[15]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[16]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[9]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[17]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[18]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[19]
GSK2110183	DMZHB37	leukaemia	2A60-2B33	Phase 2	[20]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[21]
PMID28460551-Compound-2	DM4DOUB	N. A.	N. A.	Patented	[22]

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Na(+)/Cl(-) betaine/GABA transporter (SLC6A12)	DTBPTJF	S6A12_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Betaine--homocysteine S-methyltransferase 1 (BHMT)	OTYB6PXZ	BHMT1_HUMAN	Regulation of Drug Effects	[4]
E3 ubiquitin-protein ligase MARCHF6 (MARCHF6)	OTBTA03N	MARH6_HUMAN	Protein Interaction/Cellular Processes	[5]

References

• [1] Betaine FDA Label
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4550).
• [3] Deletion of the betaine-GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult mice. Epilepsy Res. 2011 Jun;95(1-2):70-81.
• [4] Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-homocysteine methyltransferase. J Biol Chem. 2008 Apr 4;283(14):8939-45. doi: 10.1074/jbc.M710449200. Epub 2008 Jan 29.
• [5] Cholesterol increases protein levels of the E3 ligase MARCH6 and thereby stimulates protein degradation. J Biol Chem. 2019 Feb 15;294(7):2436-2448. doi: 10.1074/jbc.RA118.005069. Epub 2018 Dec 13.
• [6] The Transporter Classification Database (TCDB): recent advances. Nucleic Acids Res. 2016 Jan 4;44(D1):D372-9. (ID: 2.A.22.3.1)
• [7] Interpreting metabolomic profiles using unbiased pathway models. PLoS Comput Biol. 2010 Feb 26;6(2):e1000692.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] 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.
• [14] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [15] All-trans-retinoic acid intensifies endoplasmic reticulum stress in N-acetylglucosaminyltransferase V repressed human hepatocarcinoma cells by perturbing homocysteine metabolism. J Cell Biochem. 2010 Feb 15;109(3):468-77.
• [16] 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.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Interplay between cellular methyl metabolism and adaptive efflux during oncogenic transformation from chronic arsenic exposure in human cells. J Biol Chem. 2008 Jul 11;283(28):19342-50.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [21] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [22] 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.