Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZHY6R)

• DTT Name: Glycogen phosphorylase muscle form (GP)
• Synonyms: Muscle glycogen phosphorylase; Glycogen phosphorylase, muscle form; Glycogen phosphorylase b
• Gene Name: PYGM
• DTT Type: Patented-recorded target; [1]
• BioChemical Class: Glycosyltransferases
• UniProt ID: PYGM_HUMAN
• TTD ID: T98062
• EC Number: EC 2.4.1.1
• Sequence:
  MSRPLSDQEKRKQISVRGLAGVENVTELKKNFNRHLHFTLVKDRNVATPRDYYFALAHTV
  RDHLVGRWIRTQQHYYEKDPKRIYYLSLEFYMGRTLQNTMVNLALENACDEATYQLGLDM
  EELEEIEEDAGLGNGGLGRLAACFLDSMATLGLAAYGYGIRYEFGIFNQKISGGWQMEEA
  DDWLRYGNPWEKARPEFTLPVHFYGHVEHTSQGAKWVDTQVVLAMPYDTPVPGYRNNVVN
  TMRLWSAKAPNDFNLKDFNVGGYIQAVLDRNLAENISRVLYPNDNFFEGKELRLKQEYFV
  VAATLQDIIRRFKSSKFGCRDPVRTNFDAFPDKVAIQLNDTHPSLAIPELMRILVDLERM
  DWDKAWDVTVRTCAYTNHTVLPEALERWPVHLLETLLPRHLQIIYEINQRFLNRVAAAFP
  GDVDRLRRMSLVEEGAVKRINMAHLCIAGSHAVNGVARIHSEILKKTIFKDFYELEPHKF
  QNKTNGITPRRWLVLCNPGLAEVIAERIGEDFISDLDQLRKLLSFVDDEAFIRDVAKVKQ
  ENKLKFAAYLEREYKVHINPNSLFDIQVKRIHEYKRQLLNCLHVITLYNRIKREPNKFFV
  PRTVMIGGKAAPGYHMAKMIIRLVTAIGDVVNHDPAVGDRLRVIFLENYRVSLAEKVIPA
  ADLSEQISTAGTEASGTGNMKFMLNGALTIGTMDGANVEMAEEAGEENFFIFGMRVEDVD
  KLDQRGYNAQEYYDRIPELRQVIEQLSSGFFSPKQPDLFKDIVNMLMHHDRFKVFADYED
  YIKCQEKVSALYKNPREWTRMVIRNIATSGKFSSDRTIAQYAREIWGVEPSRQRLPAPDE
  AI
• Function: Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties. Phosphorylase is an important allosteric enzyme in carbohydrate metabolism.
• KEGG Pathway:
  Starch and sucrose metabolism (hsa00500)
  Metabolic pathways (hsa01100)
  Insulin signaling pathway (hsa04910)
  Glucagon signaling pathway (hsa04922)
• Reactome Pathway: Glycogen breakdown (glycogenolysis) (R-HSA-70221)
• BioCyc Pathway: MetaCyc:HS00949-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
URSOLIC ACID	DM4SOAW	Metabolic syndrome x	5C50-5D2Z	Phase 2	[2]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JTT-651	DMGP42Q	Type-2 diabetes	5A11	Discontinued in Phase 1	[1]

41 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1-D-glucopyranosyl cytosine	DM4NBUH	Discovery agent	N.A.	Investigative	[3]
1-D-glucopyranosyl uracil	DM90ULM	Discovery agent	N.A.	Investigative	[3]
1-Deoxy-1-Methoxycarbamido-Beta-D-Glucopyranose	DMOEQDP	Discovery agent	N.A.	Investigative	[4]
1-N-Acetyl-Beta-D-Glucosamine	DMF87Z5	Discovery agent	N.A.	Investigative	[4]
2-Deoxy-Glucose-6-Phosphate	DMMPL3D	Discovery agent	N.A.	Investigative	[4]
2-Hydroxyiminoolean-12-en-28-oic acid	DMNXV2I	Discovery agent	N.A.	Investigative	[2]
2-Hydroxyiminours-12-en-28-oic acid	DMDKF03	Discovery agent	N.A.	Investigative	[2]
2-isooleanolic acid	DMOVRX7	Discovery agent	N.A.	Investigative	[2]
2-isoursolic acid	DMEZFKS	Discovery agent	N.A.	Investigative	[2]
2-Oxoolean-12-en-28-oic acid	DMDMK81	Discovery agent	N.A.	Investigative	[2]
23-hydroxybetulinic acid	DM27GH0	Discovery agent	N.A.	Investigative	[5]
2alpha-Hydroxyolean-12-en-28-oic acid	DMHY2RA	Discovery agent	N.A.	Investigative	[2]
2alpha-Hydroxyurs-12-en-28-oic acid	DM1RSCP	Discovery agent	N.A.	Investigative	[2]
2beta,3alpha-dihydroxyolean-12-en-28-oic acid	DMV4OY2	Discovery agent	N.A.	Investigative	[6]
2beta,3alpha-dihydroxyurs-12-en-28-oic acid	DMU4Q8C	Discovery agent	N.A.	Investigative	[6]
3alpha-Hydroxyurs-12-en-28-oic Acid	DMV6OPB	Discovery agent	N.A.	Investigative	[5]
4-{2-[(3-Nitrobenzoyl)Amino]Phenoxy}Phthalic Acid	DMMGHNA	Discovery agent	N.A.	Investigative	[7]
Acurea	DMMQKCV	Discovery agent	N.A.	Investigative	[8]
Alpha-D-Glucopyranosyl-2-Carboxylic Acid Amide	DMD2TPA	Discovery agent	N.A.	Investigative	[4]
Alpha-D-Glucose-1-Phosphate	DMU36HT	Discovery agent	N.A.	Investigative	[4]
Alpha-D-Glucose-6-Phosphate	DMR0EVN	Discovery agent	N.A.	Investigative	[4]
ASIATIC ACID	DMT8Y65	Discovery agent	N.A.	Investigative	[5]
Benzyl 2-hydroxyiminoolean-12-en-28-oate	DMT3JYE	Discovery agent	N.A.	Investigative	[2]
Beta-D-Glucopyranose Spirohydantoin	DMZ2BR9	Discovery agent	N.A.	Investigative	[4]
Beta-D-Glucose	DM5IHYP	Discovery agent	N.A.	Investigative	[4]
BETULIN	DMGQRON	Discovery agent	N.A.	Investigative	[5]
C-(1-Azido-Alpha-D-Glucopyranosyl) Formamide	DMMPXHQ	Discovery agent	N.A.	Investigative	[9]
C-(1-Hydrogyl-Beta-D-Glucopyranosyl) Formamide	DM3VF9M	Discovery agent	N.A.	Investigative	[4]
Ethyl 2beta-hydroxyolean-12-en-28-oate	DMPUCMV	Discovery agent	N.A.	Investigative	[2]
Fluoro-Phosphite Ion	DMIRBYE	Discovery agent	N.A.	Investigative	[4]
Heptulose-2-Phosphate	DMIAQX4	Discovery agent	N.A.	Investigative	[4]
Indirubin-5-sulfonate	DM08VHZ	Discovery agent	N.A.	Investigative	[4]
Inosinic Acid	DMLR86H	Discovery agent	N.A.	Investigative	[4]
L-serine-O-phosphate	DMTJ1NH	Discovery agent	N.A.	Investigative	[4]
N'-Pyridoxyl-Lysine-5'-Monophosphate	DM3ZHBO	Discovery agent	N.A.	Investigative	[4]
N-Acetyl-N'-Beta-D-Glucopyranosyl Urea	DMUNCFQ	Discovery agent	N.A.	Investigative	[9]
N-Benzoyl-N'-Beta-D-Glucopyranosyl Urea	DM7U81L	Discovery agent	N.A.	Investigative	[4]
N-Butyl 2beta-hydroxyolean-12-en-28-oate	DMAQT6S	Discovery agent	N.A.	Investigative	[2]
Nojirimycine Tetrazole	DMYZRTB	Discovery agent	N.A.	Investigative	[7]
OLEANOLIC_ACID	DMWDMJ3	Discovery agent	N.A.	Investigative	[5]
Oleanonic acid	DMYPJC3	Discovery agent	N.A.	Investigative	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	2.69E-01	-0.23	-0.14

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026877)
• [2] Synthesis of 3-deoxypentacyclic triterpene derivatives as inhibitors of glycogen phosphorylase. J Nat Prod. 2009 Aug;72(8):1414-8.
• [3] 1-(3-Deoxy-3-fluoro-beta-d-glucopyranosyl) pyrimidine derivatives as inhibitors of glycogen phosphorylase b: Kinetic, crystallographic and modellin... Bioorg Med Chem. 2010 May 15;18(10):3413-25.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystal... J Med Chem. 2008 Jun 26;51(12):3540-54.
• [6] Practical synthesis of bredemolic acid, a natural inhibitor of glycogen phosphorylase. J Nat Prod. 2008 Nov;71(11):1877-80.
• [7] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [8] Binding of N-acetyl-N '-beta-D-glucopyranosyl urea and N-benzoyl-N '-beta-D-glucopyranosyl urea to glycogen phosphorylase b: kinetic and crystallographic studies. Eur J Biochem. 2002 Mar;269(6):1684-96.
• [9] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.