Target Information
| Target General Information | Top | |||||
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| Target ID |
T89918
(Former ID: TTDR01240)
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| Target Name |
Glycinamide ribonucleotide formyltransferase (GART)
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| Synonyms |
Trifunctional purine biosynthetic protein adenosine-3; PRGS; PGFT
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| Gene Name |
GART
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| Function |
A trifunctional polypeptide. Has Phosphoribosylamineglycine ligase, Phosphoribosylglycinamide formyltransferase, AIR synthetase (FGAM cyclase) activity which is required for de novo purine biosynthesis.
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| BioChemical Class |
Carbon-nitrogen ligase
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| UniProt ID | ||||||
| Sequence |
MAARVLIIGSGGREHTLAWKLAQSHHVKQVLVAPGNAGTACSEKISNTAISISDHTALAQ
FCKEKKIEFVVVGPEAPLAAGIVGNLRSAGVQCFGPTAEAAQLESSKRFAKEFMDRHGIP TAQWKAFTKPEEACSFILSADFPALVVKASGLAAGKGVIVAKSKEEACKAVQEIMQEKAF GAAGETIVIEELLDGEEVSCLCFTDGKTVAPMPPAQDHKRLLEGDGGPNTGGMGAYCPAP QVSNDLLLKIKDTVLQRTVDGMQQEGTPYTGILYAGIMLTKNGPKVLEFNCRFGDPECQV ILPLLKSDLYEVIQSTLDGLLCTSLPVWLENHTALTVVMASKGYPGDYTKGVEITGFPEA QALGLEVFHAGTALKNGKVVTHGGRVLAVTAIRENLISALEEAKKGLAAIKFEGAIYRKD VGFRAIAFLQQPRSLTYKESGVDIAAGNMLVKKIQPLAKATSRSGCKVDLGGFAGLFDLK AAGFKDPLLASGTDGVGTKLKIAQLCNKHDTIGQDLVAMCVNDILAQGAEPLFFLDYFSC GKLDLSVTEAVVAGIAKACGKAGCALLGGETAEMPDMYPPGEYDLAGFAVGAMERDQKLP HLERITEGDVVVGIASSGLHSNGFSLVRKIVAKSSLQYSSPAPDGCGDQTLGDLLLTPTR IYSHSLLPVLRSGHVKAFAHITGGGLLENIPRVLPEKLGVDLDAQTWRIPRVFSWLQQEG HLSEEEMARTFNCGVGAVLVVSKEQTEQILRDIQQHKEEAWVIGSVVARAEGSPRVKVKN LIESMQINGSVLKNGSLTNHFSFEKKKARVAVLISGTGSNLQALIDSTREPNSSAQIDIV ISNKAAVAGLDKAERAGIPTRVINHKLYKNRVEFDSAIDLVLEEFSIDIVCLAGFMRILS GPFVQKWNGKMLNIHPSLLPSFKGSNAHEQALETGVTVTGCTVHFVAEDVDAGQIILQEA VPVKRGDTVATLSERVKLAEHKIFPAALQLVASGTVQLGENGKICWVKEE Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | PELITREXOL | Drug Info | Phase 2 | Solid tumour/cancer | [2] | |
| 2 | LY309887 | Drug Info | Phase 1 | Solid tumour/cancer | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 9 Inhibitor drugs | + | ||||
| 1 | PELITREXOL | Drug Info | [1], [4] | |||
| 2 | LY309887 | Drug Info | [5], [6] | |||
| 3 | (10r)-10-Formyl-5,8,10-Trideazafolic Acid | Drug Info | [7] | |||
| 4 | 10-CF3C(OH)2-DDACTHF | Drug Info | [7] | |||
| 5 | 10-Formyl-5,8,10-Trideazafolic Acid | Drug Info | [7] | |||
| 6 | 10-trifluoroacetyl-DDACTHF | Drug Info | [8] | |||
| 7 | Dideazaacyclotetrahydrofolic acid | Drug Info | [9] | |||
| 8 | Dideazafolate | Drug Info | [10] | |||
| 9 | Glycinamide Ribonucleotide | Drug Info | [7] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 3 BioCyc Pathways | + | ||||
| 1 | Purine nucleotides de novo biosynthesis | |||||
| 2 | 5-aminoimidazole ribonucleotide biosynthesis | |||||
| 3 | Tetrahydrofolate salvage from 5,10-methenyltetrahydrofolate | |||||
| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Purine metabolism | |||||
| 2 | One carbon pool by folate | |||||
| 3 | Metabolic pathways | |||||
| 4 | Biosynthesis of antibiotics | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | TCR Signaling Pathway | |||||
| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | De novo purine biosynthesis | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Purine Metabolism | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Purine ribonucleoside monophosphate biosynthesis | |||||
| WikiPathways | [+] 3 WikiPathways | + | ||||
| 1 | One Carbon Metabolism | |||||
| 2 | Metabolism of nucleotides | |||||
| 3 | Folate Metabolism | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 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. | |||||
| REF 2 | ClinicalTrials.gov (NCT00078468) Study of the GARFT Inhibitor AG2037 in Patients With Metastatic Colorectal Cancer Who Failed Treatment. U.S. National Institutes of Health. | |||||
| REF 3 | Phase I and pharmacokinetic study of LY309887: a specific inhibitor of purine biosynthesis. Cancer Chemother Pharmacol. 2001 Jun;47(6):525-31. | |||||
| REF 4 | Phase I study of AG2034, a targeted GARFT inhibitor, administered once every 3 weeks. Cancer Chemother Pharmacol. 2000;45(5):423-7. | |||||
| REF 5 | New antimetabolites in cancer chemotherapy and their clinical impact. Br J Cancer. 1998;78 Suppl 3:1-7. | |||||
| REF 6 | Cellular pharmacology of MTA: a correlation of MTA-induced cellular toxicity and in vitro enzyme inhibition with its effect on intracellular folate and nucleoside triphosphate pools in CCRF-CEM cells. Semin Oncol. 1999 Apr;26(2 Suppl 6):48-54. | |||||
| REF 7 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 8 | Discovery of a potent, nonpolyglutamatable inhibitor of glycinamide ribonucleotide transformylase. J Med Chem. 2006 May 18;49(10):2998-3002. | |||||
| REF 9 | Asymmetric synthesis of inhibitors of glycinamide ribonucleotide transformylase. J Med Chem. 2008 Sep 11;51(17):5441-8. | |||||
| REF 10 | N10-substituted 5,8-dideazafolate inhibitors of glycinamide ribonucleotide transformylase. J Med Chem. 1987 Jul;30(7):1254-6. | |||||
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