Details of Drug Off-Target (DOT)

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

• DOT Name: Hypoxanthine-guanine phosphoribosyltransferase (HPRT1)
• Synonyms: HGPRT; HGPRTase; EC 2.4.2.8
• Gene Name: HPRT1
• Related Disease:
  Hypoxanthine guanine phosphoribosyltransferase partial deficiency
  Lesch-Nyhan syndrome
• UniProt ID: HPRT_HUMAN
• PDB ID: 1BZY; 1D6N; 1HMP; 1Z7G; 2VFA; 3GEP; 3GGC; 3GGJ; 4IJQ; 4KN6; 4RAB; 4RAC; 4RAD; 4RAN; 4RAO; 4RAQ; 5BRN; 5BSK; 5HIA; 5W8V; 6BNJ; 7SAN
• EC Number: 2.4.2.8
• Pfam ID: PF00156
• Sequence:
  MATRSPGVVISDDEPGYDLDLFCIPNHYAEDLERVFIPHGLIMDRTERLARDVMKEMGGH
  HIVALCVLKGGYKFFADLLDYIKALNRNSDRSIPMTVDFIRLKSYCNDQSTGDIKVIGGD
  DLSTLTGKNVLIVEDIIDTGKTMQTLLSLVRQYNPKMVKVASLLVKRTPRSVGYKPDFVG
  FEIPDKFVVGYALDYNEYFRDLNHVCVISETGKAKYKA
• Function: Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway:
  Defective HPRT1 disrupts guanine and hypoxanthine salvage (R-HSA-9734281)
  Azathioprine ADME (R-HSA-9748787)
  Purine salvage (R-HSA-74217)
• BioCyc Pathway: MetaCyc:HS09275-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypoxanthine guanine phosphoribosyltransferase partial deficiency	DISH99SV	Definitive	X-linked recessive	[1]
Lesch-Nyhan syndrome	DISGXKU7	Definitive	X-linked	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Hypoxanthine-guanine phosphoribosyltransferase (HPRT1) increases the Cytogenetic abnormality ADR of Etoposide.	[30]
Thioguanine	DM7NKEV	Approved	Hypoxanthine-guanine phosphoribosyltransferase (HPRT1) decreases the response to substance of Thioguanine.	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the mutagenesis of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[10]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[11]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the mutagenesis of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[12]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the mutagenesis of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[13]
Fructose	DM43AN2	Approved	Fructose decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[14]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[15]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[16]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[17]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[18]
T83193	DMHO29Y	Patented	T83193 decreases the mutagenesis of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[22]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[23]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[25]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[26]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[14]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the mutagenesis of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[27]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde decreases the mutagenesis of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[20]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the mutagenesis of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[28]
Lead acetate	DML0GZ2	Investigative	Lead acetate decreases the activity of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[29]

2 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 Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Hypoxanthine-guanine phosphoribosyltransferase (HPRT1).	[24]

References

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