Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZFTY4)

• DTT Name: Amidophosphoribosyltransferase (PPAT)
• Synonyms: Glutamine phosphoribosylpyrophosphate amidotransferase; GPAT; ATase
• Gene Name: PPAT
• DTT Type: Successful target; [1]
• BioChemical Class: Short-chain dehydrogenases reductase
• UniProt ID: PUR1_HUMAN
• TTD ID: T97713
• EC Number: EC 2.4.2.14
• Sequence:
  MELEELGIREECGVFGCIASGEWPTQLDVPHVITLGLVGLQHRGQESAGIVTSDGSSVPT
  FKSHKGMGLVNHVFTEDNLKKLYVSNLGIGHTRYATTGKCELENCQPFVVETLHGKIAVA
  HNGELVNAARLRKKLLRHGIGLSTSSDSEMITQLLAYTPPQEQDDTPDWVARIKNLMKEA
  PTAYSLLIMHRDVIYAVRDPYGNRPLCIGRLIPVSDINDKEKKTSETEGWVVSSESCSFL
  SIGARYYREVLPGEIVEISRHNVQTLDIISRSEGNPVAFCIFEYVYFARPDSMFEDQMVY
  TVRYRCGQQLAIEAPVDADLVSTVPESATPAALAYAGKCGLPYVEVLCKNRYVGRTFIQP
  NMRLRQLGVAKKFGVLSDNFKGKRIVLVDDSIVRGNTISPIIKLLKESGAKEVHIRVASP
  PIKYPCFMGINIPTKEELIANKPEFDHLAEYLGANSVVYLSVEGLVSSVQEGIKFKKQKE
  KKHDIMIQENGNGLECFEKSGHCTACLTGKYPVELEW
• Function: Catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) into 5-phosphoribosyl-1-amine (PRA), using the amine group from a glutamine side-chain.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)
• BioCyc Pathway: MetaCyc:HS05157-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Azathioprine	DMMZSXQ	Lupus nephritis	4A40.0Y	Approved	[1]
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[2]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
6-Chloropurine Riboside, 5'-Monophosphate	DMWB43U	Discovery agent	N.A.	Investigative	[3]
Mycophenolic bis(sulfonamide)	DMUQP3J	Discovery agent	N.A.	Investigative	[4]
Mycophenolic hydroxamic acid	DM4YRAH	Discovery agent	N.A.	Investigative	[5]
Tiazofurin adenine dinucleotide	DMEFVPH	Discovery agent	N.A.	Investigative	[6]

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Amidophosphoribosyltransferase (GPAT) DME Info
• Gene Name: PPAT

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[7]

References

• [1] IMPDH activity in thiopurine-treated patients with inflammatory bowel disease - relation to TPMT activity and metabolite concentrations. Br J Clin Pharmacol. 2008 Jan;65(1):69-77.
• [2] 6-mercaptopurine (6-MP) induces p53-mediated apoptosis of neural progenitor cells in the developing fetal rodent brain. Neurotoxicol Teratol. 2009 Jul-Aug;31(4):198-202.
• [3] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [4] Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: inhibition of inosine monophosphate dehydrogenase. Bioorg Med Chem. 2008 Aug 1;16(15):7462-9.
• [5] Structure-activity relationships for inhibition of inosine monophosphate dehydrogenase and differentiation induction of K562 cells among the mycoph... Bioorg Med Chem. 2010 Nov 15;18(22):8106-11.
• [6] Dual inhibitors of inosine monophosphate dehydrogenase and histone deacetylases for cancer treatment. J Med Chem. 2007 Dec 27;50(26):6685-91.
• [7] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150653776)