Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTEXB9Z)

• DTT Name: Glycinamide ribonucleotide formyltransferase (GART)
• Synonyms: Trifunctional purine biosynthetic protein adenosine-3; PRGS; PGFT
• Gene Name: GART
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Carbon-nitrogen ligase
• UniProt ID: PUR2_HUMAN
• TTD ID: T89918
• Sequence:
  MAARVLIIGSGGREHTLAWKLAQSHHVKQVLVAPGNAGTACSEKISNTAISISDHTALAQ
  FCKEKKIEFVVVGPEAPLAAGIVGNLRSAGVQCFGPTAEAAQLESSKRFAKEFMDRHGIP
  TAQWKAFTKPEEACSFILSADFPALVVKASGLAAGKGVIVAKSKEEACKAVQEIMQEKAF
  GAAGETIVIEELLDGEEVSCLCFTDGKTVAPMPPAQDHKRLLEGDGGPNTGGMGAYCPAP
  QVSNDLLLKIKDTVLQRTVDGMQQEGTPYTGILYAGIMLTKNGPKVLEFNCRFGDPECQV
  ILPLLKSDLYEVIQSTLDGLLCTSLPVWLENHTALTVVMASKGYPGDYTKGVEITGFPEA
  QALGLEVFHAGTALKNGKVVTHGGRVLAVTAIRENLISALEEAKKGLAAIKFEGAIYRKD
  VGFRAIAFLQQPRSLTYKESGVDIAAGNMLVKKIQPLAKATSRSGCKVDLGGFAGLFDLK
  AAGFKDPLLASGTDGVGTKLKIAQLCNKHDTIGQDLVAMCVNDILAQGAEPLFFLDYFSC
  GKLDLSVTEAVVAGIAKACGKAGCALLGGETAEMPDMYPPGEYDLAGFAVGAMERDQKLP
  HLERITEGDVVVGIASSGLHSNGFSLVRKIVAKSSLQYSSPAPDGCGDQTLGDLLLTPTR
  IYSHSLLPVLRSGHVKAFAHITGGGLLENIPRVLPEKLGVDLDAQTWRIPRVFSWLQQEG
  HLSEEEMARTFNCGVGAVLVVSKEQTEQILRDIQQHKEEAWVIGSVVARAEGSPRVKVKN
  LIESMQINGSVLKNGSLTNHFSFEKKKARVAVLISGTGSNLQALIDSTREPNSSAQIDIV
  ISNKAAVAGLDKAERAGIPTRVINHKLYKNRVEFDSAIDLVLEEFSIDIVCLAGFMRILS
  GPFVQKWNGKMLNIHPSLLPSFKGSNAHEQALETGVTVTGCTVHFVAEDVDAGQIILQEA
  VPVKRGDTVATLSERVKLAEHKIFPAALQLVASGTVQLGENGKICWVKEE
• Function: A trifunctional polypeptide. Has Phosphoribosylamineglycine ligase, Phosphoribosylglycinamide formyltransferase, AIR synthetase (FGAM cyclase) activity which is required for de novo purine biosynthesis.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  One carbon pool by folate (hsa00670)
  Metabolic pathways (hsa01100)
  Biosynthesis of antibiotics (hsa01130)
• Reactome Pathway: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)
• BioCyc Pathway: MetaCyc:HS08358-MON

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PELITREXOL	DMR6USG	Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]
LY309887	DMJPCHK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(10r)-10-Formyl-5,8,10-Trideazafolic Acid	DMVTLF9	Discovery agent	N.A.	Investigative	[3]
10-CF3C(OH)2-DDACTHF	DMQOUJ7	Discovery agent	N.A.	Investigative	[3]
10-Formyl-5,8,10-Trideazafolic Acid	DMEBHML	Discovery agent	N.A.	Investigative	[3]
10-trifluoroacetyl-DDACTHF	DMEAGI6	Discovery agent	N.A.	Investigative	[4]
Dideazaacyclotetrahydrofolic acid	DM9WU3R	Discovery agent	N.A.	Investigative	[5]
Dideazafolate	DMAIOC9	Discovery agent	N.A.	Investigative	[6]
Glycinamide Ribonucleotide	DMW180Y	Discovery agent	N.A.	Investigative	[3]

References

• [1] Results of 2 phase I studies of intravenous (iv) pelitrexol (AG2037), a glycinamide ribonucleotide formyltransferase (GARFT) inhibitor, in patients (pts) with solid tumors. J Clin Oncol (Meeting Abstracts) July 2004 vol. 22 no. 14_suppl 3075.
• [2] New antimetabolites in cancer chemotherapy and their clinical impact. Br J Cancer. 1998;78 Suppl 3:1-7.
• [3] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [4] Discovery of a potent, nonpolyglutamatable inhibitor of glycinamide ribonucleotide transformylase. J Med Chem. 2006 May 18;49(10):2998-3002.
• [5] Asymmetric synthesis of inhibitors of glycinamide ribonucleotide transformylase. J Med Chem. 2008 Sep 11;51(17):5441-8.
• [6] N10-substituted 5,8-dideazafolate inhibitors of glycinamide ribonucleotide transformylase. J Med Chem. 1987 Jul;30(7):1254-6.