Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQHB52T)

• DOT Name: Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1)
• Synonyms: P5C reductase 1; P5CR 1; EC 1.5.1.2
• Gene Name: PYCR1
• Related Disease:
  Autosomal recessive cutis laxa type 2B
  PYCR1-related de Barsy syndrome
  Adult hepatocellular carcinoma
  B-cell neoplasm
  Benign prostatic hyperplasia
  Cockayne syndrome
  Colorectal carcinoma
  Congenital disorder of glycosylation
  Familial Alzheimer disease
  Hutchinson-Gilford progeria syndrome
  Kidney cancer
  Liver cancer
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Measles
  Neoplasm
  Non-small-cell lung cancer
  Pancreatitis
  Papillary renal cell carcinoma
  Premature aging syndrome
  Prostate cancer
  Prostate carcinoma
  Renal carcinoma
  Breast cancer
  Breast carcinoma
  Castration-resistant prostate carcinoma
  Clear cell renal carcinoma
  Corpus callosum, agenesis of
  Renal cell carcinoma
  Geroderma osteodysplastica
  Melanoma
  Advanced cancer
  Colitis
  De Barsy syndrome
  Hepatocellular carcinoma
  Intellectual disability
  Psychotic disorder
• UniProt ID: P5CR1_HUMAN
• PDB ID: 2GER; 2GR9; 2GRA; 2IZZ; 5UAT; 5UAU; 5UAV; 5UAW; 5UAX; 6XOZ; 6XP0; 6XP1; 6XP2; 6XP3; 8DKG
• EC Number: 1.5.1.2
• Pfam ID: PF03807 ; PF14748
• Sequence:
  MSVGFIGAGQLAFALAKGFTAAGVLAAHKIMASSPDMDLATVSALRKMGVKLTPHNKETV
  QHSDVLFLAVKPHIIPFILDEIGADIEDRHIVVSCAAGVTISSIEKKLSAFRPAPRVIRC
  MTNTPVVVREGATVYATGTHAQVEDGRLMEQLLSSVGFCTEVEEDLIDAVTGLSGSGPAY
  AFTALDALADGGVKMGLPRRLAVRLGAQALLGAAKMLLHSEQHPGQLKDNVSSPGGATIH
  ALHVLESGGFRSLLINAVEASCIRTRELQSMADQEQVSPAAIKKTILDKVKLDSPAGTAL
  SPSGHTKLLPRSLAPAGKD
• Function: Housekeeping enzyme that catalyzes the last step in proline biosynthesis. Can utilize both NAD and NADP, but has higher affinity for NAD. Involved in the cellular response to oxidative stress.
• KEGG Pathway:
  Arginine and proline metabolism (hsa00330)
  Metabolic pathways (hsa01100)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway: Glutamate and glutamine metabolism (R-HSA-8964539)
• BioCyc Pathway: MetaCyc:HS06848-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive cutis laxa type 2B	DIS7URGV	Definitive	Autosomal recessive	[1]
PYCR1-related de Barsy syndrome	DIS9EFII	Definitive	Autosomal recessive	[2]
Adult hepatocellular carcinoma	DIS6ZPAI	Strong	Biomarker	[3]
B-cell neoplasm	DISVY326	Strong	Altered Expression	[4]
Benign prostatic hyperplasia	DISI3CW2	Strong	Genetic Variation	[5]
Cockayne syndrome	DISW6GL2	Strong	Genetic Variation	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Congenital disorder of glycosylation	DIS400QP	Strong	Biomarker	[8]
Familial Alzheimer disease	DISE75U4	Strong	Genetic Variation	[9]
Hutchinson-Gilford progeria syndrome	DISY55BU	Strong	Genetic Variation	[10]
Kidney cancer	DISBIPKM	Strong	Biomarker	[11]
Liver cancer	DISDE4BI	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[4]
Lung carcinoma	DISTR26C	Strong	Biomarker	[4]
Measles	DISXSUID	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[15]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[16]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[17]
Premature aging syndrome	DIS51AGT	Strong	Genetic Variation	[18]
Prostate cancer	DISF190Y	Strong	Altered Expression	[4]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[4]
Renal carcinoma	DISER9XT	Strong	Biomarker	[11]
Breast cancer	DIS7DPX1	moderate	Biomarker	[19]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[19]
Castration-resistant prostate carcinoma	DISVGAE6	moderate	Biomarker	[20]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[21]
Corpus callosum, agenesis of	DISO9P40	moderate	Genetic Variation	[22]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[21]
Geroderma osteodysplastica	DISFPJ78	Supportive	Autosomal recessive	[23]
Melanoma	DIS1RRCY	Disputed	Altered Expression	[24]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[25]
Colitis	DISAF7DD	Limited	Altered Expression	[26]
De Barsy syndrome	DISUQYF3	Limited	Genetic Variation	[27]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[14]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[28]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[43]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[32]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[33]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[34]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[35]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[36]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[37]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[38]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[39]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[40]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[41]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[34]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[34]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[34]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[41]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[42]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[44]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[45]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[47]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pyrroline-5-carboxylate reductase 1, mitochondrial (PYCR1).	[40]

References

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