Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG7NW98)

• DOT Name: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2)
• Synonyms: 6PF-2-K/Fru-2,6-P2ase 2; PFK/FBPase 2; 6PF-2-K/Fru-2,6-P2ase heart-type isozyme
• Gene Name: PFKFB2
• UniProt ID: F262_HUMAN
• PDB ID: 5HTK
• EC Number: 2.7.1.105; 3.1.3.46
• Pfam ID: PF01591 ; PF00300
• Sequence:
  MSGASSSEQNNNSYETKTPNLRMSEKKCSWASYMTNSPTLIVMIGLPARGKTYVSKKLTR
  YLNWIGVPTKVFNLGVYRREAVKSYKSYDFFRHDNEEAMKIRKQCALVALEDVKAYLTEE
  NGQIAVFDATNTTRERRDMILNFAEQNSFKVFFVESVCDDPDVIAANILEVKVSSPDYPE
  RNRENVMEDFLKRIECYKVTYRPLDPDNYDKDLSFIKVINVGQRFLVNRVQDYIQSKIVY
  YLMNIHVQPRTIYLCRHGESEFNLLGKIGGDSGLSVRGKQFAQALRKFLEEQEITDLKVW
  TSQLKRTIQTAESLGVPYEQWKILNEIDAGVCEEMTYAEIEKRYPEEFALRDQEKYLYRY
  PGGESYQDLVQRLEPVIMELERQGNVLVISHQAVMRCLLAYFLDKGADELPYLRCPLHTI
  FKLTPVAYGCKVETIKLNVEAVNTHRDKPTNNFPKNQTPVRMRRNSFTPLSSSNTIRRPR
  NYSVGSRPLKPLSPLRAQDMQEGAD
• Function: Synthesis and degradation of fructose 2,6-bisphosphate.
• Tissue Specificity: Heart.
• KEGG Pathway:
  Fructose and mannose metabolism (hsa00051)
  Metabolic pathways (hsa01100)
  AMPK sig.ling pathway (hsa04152)
  Thyroid hormone sig.ling pathway (hsa04919)
• Reactome Pathway: Regulation of glycolysis by fructose 2,6-bisphosphate metabolism (R-HSA-9634600)
• BioCyc Pathway: MetaCyc:HS04690-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[1]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[3]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[4]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[10]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[11]

3 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 decreases the methylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[8]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2).	[8]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [5] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [6] 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.
• [7] 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.
• [8] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [10] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [11] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.