Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT77CFJ6)

• DOT Name: Pantothenate kinase 3 (PANK3)
• Synonyms: hPanK3; EC 2.7.1.33; Pantothenic acid kinase 3
• Gene Name: PANK3
• UniProt ID: PANK3_HUMAN
• PDB ID: 2I7P; 3MK6; 3SMS; 5KPR; 5KPT; 5KPZ; 5KQ8; 5KQD; 6B3V; 6PE6; 6X4J; 6X4K; 6X4L; 7UE3; 7UE4; 7UE5; 7UE6; 7UE7; 7UE8; 7UEO; 7UEP; 7UEQ; 7UER; 7UES; 7UET; 7UEU; 7UEV; 7UEX; 7UEY
• EC Number: 2.7.1.33
• Pfam ID: PF03630
• Sequence:
  MKIKDAKKPSFPWFGMDIGGTLVKLSYFEPIDITAEEEQEEVESLKSIRKYLTSNVAYGS
  TGIRDVHLELKDLTLFGRRGNLHFIRFPTQDLPTFIQMGRDKNFSTLQTVLCATGGGAYK
  FEKDFRTIGNLHLHKLDELDCLVKGLLYIDSVSFNGQAECYYFANASEPERCQKMPFNLD
  DPYPLLVVNIGSGVSILAVHSKDNYKRVTGTSLGGGTFLGLCSLLTGCESFEEALEMASK
  GDSTQADKLVRDIYGGDYERFGLPGWAVASSFGNMIYKEKRESVSKEDLARATLVTITNN
  IGSVARMCAVNEKINRVVFVGNFLRVNTLSMKLLAYALDYWSKGQLKALFLEHEGYFGAV
  GALLGLPNFS
• Function: Catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.
• Tissue Specificity: Highly expressed in the liver.
• KEGG Pathway:
  Pantothe.te and CoA biosynthesis (hsa00770)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Coenzyme A biosynthesis (R-HSA-196783)
• BioCyc Pathway: MetaCyc:HS04372-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Pantothenate kinase 3 (PANK3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Pantothenate kinase 3 (PANK3).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pantothenate kinase 3 (PANK3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pantothenate kinase 3 (PANK3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pantothenate kinase 3 (PANK3).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Pantothenate kinase 3 (PANK3).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Pantothenate kinase 3 (PANK3).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Pantothenate kinase 3 (PANK3).	[7]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Pantothenate kinase 3 (PANK3).	[8]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Pantothenate kinase 3 (PANK3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pantothenate kinase 3 (PANK3).	[10]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Pantothenate kinase 3 (PANK3).	[11]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Pantothenate kinase 3 (PANK3).	[3]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Pantothenate kinase 3 (PANK3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pantothenate kinase 3 (PANK3).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Pantothenate kinase 3 (PANK3).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Pantothenate kinase 3 (PANK3).	[16]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Pantothenate kinase 3 (PANK3).	[17]

References

• [1] 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.
• [2] 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.
• [3] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [7] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [8] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [9] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] 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.
• [15] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.