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

General Information of Drug (ID: DMQHN7I)

• Drug Name: L-leucine Drug Info
• Synonyms: leucine; 61-90-5; (S)-2-Amino-4-methylpentanoic acid; H-Leu-OH; (S)-Leucine; (2S)-2-amino-4-methylpentanoic acid; (S)-(+)-Leucine; Leucin; L-Norvaline, 4-methyl-; (S)-2-Amino-4-methylvaleric acid; L-leucin; L-alpha-Aminoisocaproic acid; Leucin [German]; LEUCINE, L-; Leucine (VAN); leu; Leucinum; (2S)-alpha-leucine; L-(-)-2-Amino-4-methylpentanoic acid; 2-amino-4-methylvaleric acid; Leucinum [INN-Latin]; Leucine [USAN:INN]; L-Leuzin; Leucina [INN-Spanish]; Leucina [Latin,Spanish]; alpha-Aminoisocaproic acid

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 6106
  ChEBI ID: CHEBI:15603
  CAS Number: CAS 61-90-5
  TTD Drug ID: DMQHN7I
  VARIDT Drug ID: DR00303
  INTEDE Drug ID: DR2107

Molecule-Related Drug Atlas

Drug(s) Transported By L-type amino acid transporter 3 (SLC43A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-Phenylalanine	DMQXI9F	Malnutrition	5B50-5B71	Approved	[2]
L-valine	DM68RPD	Discovery agent	N.A.	Investigative	[2]
L-isoleucine	DM4B6H3	Discovery agent	N.A.	Investigative	[2]

Drug(s) Transported By L-type amino acid transporter 4 (SLC43A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-Phenylalanine	DMQXI9F	Malnutrition	5B50-5B71	Approved	[3]
L-valine	DM68RPD	Discovery agent	N.A.	Investigative	[3]
L-isoleucine	DM4B6H3	Discovery agent	N.A.	Investigative	[3]

Drug(s) Transported By L-type amino acid transporter 1 (SLC7A5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-glutamine	DM69G8X	Short bowel syndrome	KB89.1	Approved	[4]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[7]
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[8]
Pregabalin	DMDVP3B	Chronic obstructive pulmonary disease	CA22	Approved	[9]

Drug(s) Affected By Large neutral amino acids transporter small subunit 2 (SLC7A8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[10]
Selenium	DM25CGV	N. A.	N. A.	Approved	[11]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[12]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[13]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[16]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[17]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[18]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[12]

Drug(s) Affected By Amino acid transporter heavy chain SLC3A2 (SLC3A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[11]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[19]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[20]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[21]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[22]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[23]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[24]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[25]

Drug(s) Affected By ATP-binding cassette sub-family C member 8 (ABCC8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tolbutamide	DM02AWV	Advanced cancer	2A00-2F9Z	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Mifepristone	DMGZQEF	Cushing disease	5A70	Approved	[28]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[29]
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[26]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[30]
PMID28460551-Compound-2	DM4DOUB	N. A.	N. A.	Patented	[31]

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
L-type amino acid transporter 3 (SLC43A1)	DTBMSWG	LAT3_HUMAN	Substrate	[2]
L-type amino acid transporter 4 (SLC43A2)	DTK02I1	LAT4_HUMAN	Substrate	[3]
L-type amino acid transporter 1 (SLC7A5)	DT48T0N	LAT1_HUMAN	Substrate	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Leucyl-tRNA synthetase (LARS2) Main DME	DEP7BTH	SYLM_HUMAN	Substrate	[5]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Amino acid transporter heavy chain SLC3A2 (SLC3A2)	OTBR33M9	4F2_HUMAN	Regulation of Drug Effects	[6]
ATP-binding cassette sub-family C member 8 (ABCC8)	OTCWQ54I	ABCC8_HUMAN	Drug Response
Large neutral amino acids transporter small subunit 2 (SLC7A8)	OT8XXVO8	LAT2_HUMAN	Regulation of Drug Effects	[6]

References

• [1] 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: 3312).
• [2] Identification of a novel system L amino acid transporter structurally distinct from heterodimeric amino acid transporters. J Biol Chem. 2003 Oct 31;278(44):43838-45.
• [3] Anticipation of food intake induces phosphorylation switch to regulate basolateral amino acid transporter LAT4 (SLC43A2) function. J Physiol. 2019 Jan;597(2):521-542.
• [4] Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009 Feb 6;136(3):521-34.
• [5] Expression and characterization of the human mitochondrial leucyl-tRNA synthetase. Biochim Biophys Acta. 2000 Feb 29;1490(3):245-58.
• [6] Methylmercury Uptake into BeWo Cells Depends on LAT2-4F2hc, a System L Amino Acid Transporter. Int J Mol Sci. 2017 Aug 8;18(8):1730. doi: 10.3390/ijms18081730.
• [7] Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol. Sci Rep. 2017 Mar 8;7:43580.
• [8] Transport of gabapentin by LAT1 (SLC7A5). Biochem Pharmacol. 2013 Jun 1;85(11):1672-83.
• [9] Transport of Pregabalin Via L-Type Amino Acid Transporter 1 (SLC7A5) in Human Brain Capillary Endothelial Cell Line. Pharm Res. 2018 Oct 29;35(12):246.
• [10] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [11] 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.
• [12] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [13] 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.
• [14] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [15] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [16] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [17] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [18] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [19] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [20] 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.
• [21] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [22] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [23] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [24] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [25] 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.
• [26] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [27] 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.
• [28] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [29] Role of transporter genes in cisplatin resistance. In Vivo. 2008 May-Jun;22(3):279-83.
• [30] 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.
• [31] 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.