Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQW7TMB)

• DOT Name: Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1)
• Synonyms: GPD-C; GPDH-C; EC 1.1.1.8
• Gene Name: GPD1
• Related Disease: Transient infantile hypertriglyceridemia and hepatosteatosis
• UniProt ID: GPDA_HUMAN
• PDB ID: 1WPQ; 1X0V; 1X0X; 6E8Y; 6E8Z; 6E90; 6PYP
• EC Number: 1.1.1.8
• Pfam ID: PF07479 ; PF01210
• Sequence:
  MASKKVCIVGSGNWGSAIAKIVGGNAAQLAQFDPRVTMWVFEEDIGGKKLTEIINTQHEN
  VKYLPGHKLPPNVVAVPDVVQAAEDADILIFVVPHQFIGKICDQLKGHLKANATGISLIK
  GVDEGPNGLKLISEVIGERLGIPMSVLMGANIASEVADEKFCETTIGCKDPAQGQLLKEL
  MQTPNFRITVVQEVDTVEICGALKNVVAVGAGFCDGLGFGDNTKAAVIRLGLMEMIAFAK
  LFCSGPVSSATFLESCGVADLITTCYGGRNRKVAEAFARTGKSIEQLEKELLNGQKLQGP
  ETARELYSILQHKGLVDKFPLFMAVYKVCYEGQPVGEFIHCLQNHPEHM
• Function: Has glycerol-3-phosphate dehydrogenase activity.
• Tissue Specificity: Expressed in liver (at protein level).
• KEGG Pathway: Glycerophospholipid metabolism (hsa00564)
• Reactome Pathway: Synthesis of PA (R-HSA-1483166)
• BioCyc Pathway: MetaCyc:HS09586-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Transient infantile hypertriglyceridemia and hepatosteatosis	DIS9H0TD	Strong	Autosomal recessive	[1]

14 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[5]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[6]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[8]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[9]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[12]
ORG2058	DMH1M6N	Investigative	ORG2058 increases the expression of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glycerol-3-phosphate dehydrogenase , cytoplasmic (GPD1).	[10]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] 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.
• [3] 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.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [7] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [10] 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.
• [11] 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.
• [12] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [13] The antiproliferative effects of progestins in T47D breast cancer cells are tempered by progestin induction of the ETS transcription factor Elf5. Mol Endocrinol. 2010 Jul;24(7):1380-92. doi: 10.1210/me.2009-0516. Epub 2010 Jun 2.