Details of Drug Off-Target (DOT)

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

• DOT Name: Glycogen phosphorylase, muscle form (PYGM)
• Synonyms: EC 2.4.1.1; Myophosphorylase
• Gene Name: PYGM
• Related Disease: Glycogen storage disease V
• UniProt ID: PYGM_HUMAN
• PDB ID: 1Z8D
• EC Number: 2.4.1.1
• Pfam ID: PF00343
• Sequence:
  MSRPLSDQEKRKQISVRGLAGVENVTELKKNFNRHLHFTLVKDRNVATPRDYYFALAHTV
  RDHLVGRWIRTQQHYYEKDPKRIYYLSLEFYMGRTLQNTMVNLALENACDEATYQLGLDM
  EELEEIEEDAGLGNGGLGRLAACFLDSMATLGLAAYGYGIRYEFGIFNQKISGGWQMEEA
  DDWLRYGNPWEKARPEFTLPVHFYGHVEHTSQGAKWVDTQVVLAMPYDTPVPGYRNNVVN
  TMRLWSAKAPNDFNLKDFNVGGYIQAVLDRNLAENISRVLYPNDNFFEGKELRLKQEYFV
  VAATLQDIIRRFKSSKFGCRDPVRTNFDAFPDKVAIQLNDTHPSLAIPELMRILVDLERM
  DWDKAWDVTVRTCAYTNHTVLPEALERWPVHLLETLLPRHLQIIYEINQRFLNRVAAAFP
  GDVDRLRRMSLVEEGAVKRINMAHLCIAGSHAVNGVARIHSEILKKTIFKDFYELEPHKF
  QNKTNGITPRRWLVLCNPGLAEVIAERIGEDFISDLDQLRKLLSFVDDEAFIRDVAKVKQ
  ENKLKFAAYLEREYKVHINPNSLFDIQVKRIHEYKRQLLNCLHVITLYNRIKREPNKFFV
  PRTVMIGGKAAPGYHMAKMIIRLVTAIGDVVNHDPAVGDRLRVIFLENYRVSLAEKVIPA
  ADLSEQISTAGTEASGTGNMKFMLNGALTIGTMDGANVEMAEEAGEENFFIFGMRVEDVD
  KLDQRGYNAQEYYDRIPELRQVIEQLSSGFFSPKQPDLFKDIVNMLMHHDRFKVFADYED
  YIKCQEKVSALYKNPREWTRMVIRNIATSGKFSSDRTIAQYAREIWGVEPSRQRLPAPDE
  AI
• 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)
• BioCyc Pathway: MetaCyc:HS00949-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glycogen storage disease V	DISJNC0O	Strong	Autosomal recessive	[1]

1 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 Glycogen phosphorylase, muscle form (PYGM).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[4]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[5]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[3]
Daunorubicin	DMQUSBT	Approved	Daunorubicin decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[3]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[6]
Prednisone	DM2HG4X	Approved	Prednisone decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Glycogen phosphorylase, muscle form (PYGM).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Glycogen phosphorylase, muscle form (PYGM).	[11]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] 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.
• [3] Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment. Arch Toxicol. 2016 Nov;90(11):2763-2777.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch Toxicol. 2018 Apr;92(4):1507-1524.
• [6] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [7] Muscle glycogen of steroid myopathy patients. J Neurol Sci. 1996 Mar;136(1-2):192-5. doi: 10.1016/0022-510x(95)00331-u.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [10] 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.
• [11] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.