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

General Information of Drug (ID: DMU3O5H)

• Drug Name: malic acid Drug Info
• Synonyms: malate

Indication

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

• Cross-matching ID:
  PubChem CID: 525
  ChEBI ID: CHEBI:6650
  CAS Number: CAS 6915-15-7
  TTD Drug ID: DMU3O5H

Molecule-Related Drug Atlas

Drug(s) Targeting Polycystic kidney disease 2-like 1 (TRPP2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
benzamil	DM57SVW	Discovery agent	N.A.	Investigative	[5]
citric acid	DM80YI7	Discovery agent	N.A.	Investigative	[2]
flufenamate	DMN8AP0	Discovery agent	N.A.	Investigative	[5]
phenamil	DMJLUFM	Discovery agent	N.A.	Investigative	[5]

Drug(s) Affected By Malate dehydrogenase, cytoplasmic (MDH1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[6]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[7]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[8]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[9]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[10]
Dihydroartemisinin	DMBXVMZ	Malaria	1F40-1F45	Approved	[11]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[12]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[13]
Benzatropine	DMF7EXL	Parkinsonian disorder		Approved	[14]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[14]

Drug(s) Affected By Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[15]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[16]
Fructose	DM43AN2	Vomiting	MD90	Approved	[17]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[18]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[19]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Ketotifen	DM74XKS	Allergic conjunctivitis	9A60.02	Approved	[21]
Riboflavin	DM8YMWE	Acne vulgaris	ED80	Approved	[4]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[22]
Glutathione	DMAHMT9	Human immunodeficiency virus infection	1C62	Approved	[4]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Polycystic kidney disease 2-like 1 (TRPP2)	TTAHD89	PK2L1_HUMAN	Activator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Malate dehydrogenase, cytoplasmic (MDH1)	OTJEO4E8	MDHC_HUMAN	Gene/Protein Processing	[3]
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A)	OTHCDQ22	PRGC1_HUMAN	Gene/Protein Processing	[4]

References

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• [2] Transient receptor potential family members PKD1L3 and PKD2L1 form a candidate sour taste receptor. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12569-74.
• [3] Oxaloacetate enhances neuronal cell bioenergetic fluxes and infrastructure. J Neurochem. 2016 Apr;137(1):76-87. doi: 10.1111/jnc.13545. Epub 2016 Mar 11.
• [4] A cardiac-specific robotized cellular assay identified families of human ligands as inducers of PGC-1 expression and mitochondrial biogenesis. PLoS One. 2012;7(10):e46753. doi: 10.1371/journal.pone.0046753. Epub 2012 Oct 3.
• [5] 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. (Target id: 505).
• [6] 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.
• [7] Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
• [8] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [9] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [10] 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.
• [11] Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
• [12] 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.
• [13] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [14] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [15] 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.
• [16] Troglitazone induces cytotoxicity in part by promoting the degradation of peroxisome proliferator-activated receptor co-activator-1 protein. Br J Pharmacol. 2010 Oct;161(4):771-81. doi: 10.1111/j.1476-5381.2010.00900.x.
• [17] Effects of four-week high-fructose diet on gene expression in skeletal muscle of healthy men. Diabetes Metab. 2008 Feb;34(1):82-5. doi: 10.1016/j.diabet.2007.08.004. Epub 2007 Dec 11.
• [18] Glucosamine-induced endoplasmic reticulum stress affects GLUT4 expression via activating transcription factor 6 in rat and human skeletal muscle cells. Diabetologia. 2010 May;53(5):955-65. doi: 10.1007/s00125-010-1676-1. Epub 2010 Feb 18.
• [19] AMPK activator acadesine fails to alleviate isoniazid-caused mitochondrial instability in HepG2 cells. J Appl Toxicol. 2017 Oct;37(10):1219-1224. doi: 10.1002/jat.3483. Epub 2017 May 29.
• [20] 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.
• [21] Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis. Toxicol Appl Pharmacol. 2016 Jul 1;302:1-9. doi: 10.1016/j.taap.2016.04.007. Epub 2016 Apr 16.
• [22] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.