Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS1YFGR)

• DOT Name: Glycogen phosphorylase, liver form (PYGL)
• Synonyms: EC 2.4.1.1
• Gene Name: PYGL
• Related Disease:
  Glycogen storage disease VI
  Disorder of glycogen metabolism
  Gerstmann-Straussler-Scheinker syndrome
  Glycogen storage disease I
  Glycogen storage disease III
  Glycogen storage disease V
  Hepatocellular carcinoma
• UniProt ID: PYGL_HUMAN
• PDB ID: 1EM6; 1EXV; 1FA9; 1FC0; 1L5Q; 1L5R; 1L5S; 1L7X; 1XOI; 2ATI; 2QLL; 2ZB2; 3CEH; 3CEJ; 3CEM; 3DD1; 3DDS; 3DDW; 8EMS
• EC Number: 2.4.1.1
• Pfam ID: PF00343
• Sequence:
  MAKPLTDQEKRRQISIRGIVGVENVAELKKSFNRHLHFTLVKDRNVATTRDYYFALAHTV
  RDHLVGRWIRTQQHYYDKCPKRVYYLSLEFYMGRTLQNTMINLGLQNACDEAIYQLGLDI
  EELEEIEEDAGLGNGGLGRLAACFLDSMATLGLAAYGYGIRYEYGIFNQKIRDGWQVEEA
  DDWLRYGNPWEKSRPEFMLPVHFYGKVEHTNTGTKWIDTQVVLALPYDTPVPGYMNNTVN
  TMRLWSARAPNDFNLRDFNVGDYIQAVLDRNLAENISRVLYPNDNFFEGKELRLKQEYFV
  VAATLQDIIRRFKASKFGSTRGAGTVFDAFPDQVAIQLNDTHPALAIPELMRIFVDIEKL
  PWSKAWELTQKTFAYTNHTVLPEALERWPVDLVEKLLPRHLEIIYEINQKHLDRIVALFP
  KDVDRLRRMSLIEEEGSKRINMAHLCIVGSHAVNGVAKIHSDIVKTKVFKDFSELEPDKF
  QNKTNGITPRRWLLLCNPGLAELIAEKIGEDYVKDLSQLTKLHSFLGDDVFLRELAKVKQ
  ENKLKFSQFLETEYKVKINPSSMFDVQVKRIHEYKRQLLNCLHVITMYNRIKKDPKKLFV
  PRTVIIGGKAAPGYHMAKMIIKLITSVADVVNNDPMVGSKLKVIFLENYRVSLAEKVIPA
  TDLSEQISTAGTEASGTGNMKFMLNGALTIGTMDGANVEMAEEAGEENLFIFGMRIDDVA
  ALDKKGYEAKEYYEALPELKLVIDQIDNGFFSPKQPDLFKDIINMLFYHDRFKVFADYEA
  YVKCQDKVSQLYMNPKAWNTMVLKNIAASGKFSSDRTIKEYAQNIWNVEPSDLKISLSNE
  SNKVNGN
• Function: Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.
• KEGG Pathway:
  Starch and sucrose metabolism (hsa00500)
  Metabolic pathways (hsa01100)
  Necroptosis (hsa04217)
  Insulin sig.ling pathway (hsa04910)
  Glucagon sig.ling pathway (hsa04922)
  Insulin resistance (hsa04931)
• Reactome Pathway:
  Glycogen breakdown (glycogenolysis) (R-HSA-70221)
  Neutrophil degranulation (R-HSA-6798695)
• BioCyc Pathway: MetaCyc:HS02099-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glycogen storage disease VI	DIS46FMA	Definitive	Autosomal recessive	[1]
Disorder of glycogen metabolism	DISYGNOB	Strong	Biomarker	[2]
Gerstmann-Straussler-Scheinker syndrome	DISIO6KC	Strong	Genetic Variation	[3]
Glycogen storage disease I	DISY4Q9T	Strong	Genetic Variation	[4]
Glycogen storage disease III	DISTXQ1P	Strong	Genetic Variation	[4]
Glycogen storage disease V	DISJNC0O	Strong	Genetic Variation	[3]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Flavopiridol	DMKSUOI	Phase 2	Glycogen phosphorylase, liver form (PYGL) affects the binding of Flavopiridol.	[30]

23 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 Glycogen phosphorylase, liver form (PYGL).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Glycogen phosphorylase, liver form (PYGL).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Glycogen phosphorylase, liver form (PYGL).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Glycogen phosphorylase, liver form (PYGL).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Glycogen phosphorylase, liver form (PYGL).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[15]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[10]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Glycogen phosphorylase, liver form (PYGL).	[16]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Glycogen phosphorylase, liver form (PYGL).	[17]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN decreases the activity of Glycogen phosphorylase, liver form (PYGL).	[19]
ACYLINE	DM9GRTK	Phase 2	ACYLINE increases the expression of Glycogen phosphorylase, liver form (PYGL).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Glycogen phosphorylase, liver form (PYGL).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Glycogen phosphorylase, liver form (PYGL).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[27]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Glycogen phosphorylase, liver form (PYGL).	[28]
P-Coumaric Acid	DMGJSVD	Investigative	P-Coumaric Acid decreases the activity of Glycogen phosphorylase, liver form (PYGL).	[29]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Glycogen phosphorylase, liver form (PYGL).	[18]
T83193	DMHO29Y	Patented	T83193 affects the binding of Glycogen phosphorylase, liver form (PYGL).	[24]

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 affects the methylation of Glycogen phosphorylase, liver form (PYGL).	[21]

References

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