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

General Information of Drug (ID: DMH15UV)

• Drug Name: Tetrahydrofolic acid Drug Info
• Synonyms: Tetrahydrafolate; Tetrahydrofolate; Tetrahydropteroylglutamate; Tetrahydropteroylglutamic acid; BIT3012; FH4; H4PteGlu; Folate-H4; Th-folate; Tetra-H-folate; Tetrahydropteroyl mono-L-glutamate; N-(5,6,7,8-tetrahydropteroyl)-L-glutamic acid; N-(4-(((2-Amino-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)glutamic acid; N-[4-{[(2-amino-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}benzoyl]-L-glutamic acid; N-(4-(((2-Amino-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-glutamic acid; N-[4-({[(6S)-2-AMINO-4-OXO-1,4,5,6,7,8-HEXAHYDROPTERIDIN-6-YL]METHYL}AMINO)BENZOYL]-L-GLUTAMIC ACID; N-[4-({[(6S)-2-amino-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzoyl]-L-glutamic acid; (2S)-2-[[4-[(2-amino-4-oxo-5,6,7,8-tetrahydro-1H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid; (2S)-2-[[4-[[(6S)-2-amino-4-oxo-5,6,7,8-tetrahydro-1H-pteridin-6-yl]methylamino]benzoyl]amino]pentanedioic acid; (6S)-5,6,7,8-tetrahydropteroylglutamate; (6S)-H4folate; (6S)-THFA; (6S)-Tetrahydrofolic acid; (6S)-tetrahydrofolate; 2-[[4-[(2-amino-4-oxo-5,6,7,8-tetrahydro-1H-pteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid; 5,6,7,8-Tetrahydropteroyl-L-glutamic acid; 5,6,7,8-tetrahydrofolate; 5,6,7,8-tetrahydrofolic acid

Indication

Disease Entry	ICD 11	Status	REF
Malnutrition	5B50-5B71	Approved	[1]

• Therapeutic Class: Dietary supplement
• Cross-matching ID:
  PubChem CID: 135444742
  ChEBI ID: CHEBI:20506
  CAS Number: CAS 135-16-0
  TTD Drug ID: DMH15UV

Molecule-Related Drug Atlas

Drug(s) Targeting Folate receptor (FOLR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[5]

Drug(s) Affected By Insulin-like growth factor 1 receptor (IGF1R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[6]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[7]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[8]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[9]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[10]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[11]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[12]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[13]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[13]
Clodronate	DM9Y6X7	Hypercalcaemia	5B91.0	Approved	[14]

Drug(s) Affected By Mitochondrial 10-formyltetrahydrofolate dehydrogenase (ALDH1L2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[15]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[16]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[18]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[19]
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[20]
Indomethacin	DMSC4A7	Bursitis		Approved	[21]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[22]
Mitotane	DMU1GX0	Adrenocortical carcinoma	2D11.Z	Approved	[23]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[24]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Folate receptor (FOLR)	TTQOD3G	NOUNIPROTAC	Binder	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Insulin-like growth factor 1 receptor (IGF1R)	OTXJIF13	IGF1R_HUMAN	Gene/Protein Processing	[3]
Mitochondrial 10-formyltetrahydrofolate dehydrogenase (ALDH1L2)	OTCH86VF	AL1L2_HUMAN	Biotransformations	[4]

References

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• [4] Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase. Chem Biol Interact. 2011 May 30;191(1-3):129-36. doi: 10.1016/j.cbi.2011.01.008. Epub 2011 Jan 14.
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• [9] Simvastatin inhibits the proliferation of human prostate cancer PC-3 cells via down-regulation of the insulin-like growth factor 1 receptor. Biochem Biophys Res Commun. 2008 Jul 25;372(2):356-61. doi: 10.1016/j.bbrc.2008.05.043. Epub 2008 May 19.
• [10] Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
• [11] Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: therapeutic potential for ovarian cancer. Cancer Sci. 2009 Dec;100(12):2459-64.
• [12] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [15] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [16] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [17] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [18] Inter-laboratory comparison of human renal proximal tubule (HK-2) transcriptome alterations due to Cyclosporine A exposure and medium exhaustion. Toxicol In Vitro. 2009 Apr;23(3):486-99.
• [19] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [20] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [21] Anti-inflammatory agent indomethacin reduces invasion and alters metabolism in a human breast cancer cell line. Neoplasia. 2007 Mar;9(3):222-35.
• [22] 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.
• [23] Effects of mitotane on gene expression in the adrenocortical cell line NCI-H295R: a microarray study. Pharmacogenomics. 2012 Sep;13(12):1351-61. doi: 10.2217/pgs.12.116.
• [24] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.