Target Information
| Target General Information | Top | |||||
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| Target ID |
T78198
(Former ID: TTDC00091)
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| Target Name |
Purine nucleoside phosphorylase (PNP)
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| Synonyms |
PNP; Inosine phosphorylase
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| Gene Name |
PNP
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 5 Target-related Diseases | + | ||||
| 1 | Diabetes mellitus [ICD-11: 5A10] | |||||
| 2 | Gout [ICD-11: FA25] | |||||
| 3 | Psoriasis [ICD-11: EA90] | |||||
| 4 | Malignant haematopoietic neoplasm [ICD-11: 2B33] | |||||
| 5 | Mycosis fungoides [ICD-11: 2B01] | |||||
| Function |
The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta- (deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.
Click to Show/Hide
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| BioChemical Class |
Pentosyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.4.2.1
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| Sequence |
MENGYTYEDYKNTAEWLLSHTKHRPQVAIICGSGLGGLTDKLTQAQIFDYGEIPNFPRST
VPGHAGRLVFGFLNGRACVMMQGRFHMYEGYPLWKVTFPVRVFHLLGVDTLVVTNAAGGL NPKFEVGDIMLIRDHINLPGFSGQNPLRGPNDERFGDRFPAMSDAYDRTMRQRALSTWKQ MGEQRELQEGTYVMVAGPSFETVAECRVLQKLGADAVGMSTVPEVIVARHCGLRVFGFSL ITNKVIMDYESLEKANHEEVLAAGKQAAQKLEQFVSILMASIPLPDKAS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A05061 ; BADD_A06637 | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | BCX-3408 | Drug Info | Phase 2 | Plaque psoriasis | [2] | |
| 2 | Forodesine | Drug Info | Phase 1/2 | B-cell acute lymphoblastic leukaemia | [3], [4] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | CI-972 | Drug Info | Discontinued in Phase 1 | Rheumatoid arthritis | [5] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 33 Inhibitor drugs | + | ||||
| 1 | 2'3'-Dideoxyinosine | Drug Info | [6] | |||
| 2 | BCX-3408 | Drug Info | [1], [7], [8] | |||
| 3 | Forodesine | Drug Info | [9], [10], [11] | |||
| 4 | Guanosine | Drug Info | [6] | |||
| 5 | Peldesine | Drug Info | [6] | |||
| 6 | CI-972 | Drug Info | [12] | |||
| 7 | (+/-)-5'-deoxy-4'-fluoro-5'-methylthio-DADMe-ImmH | Drug Info | [13] | |||
| 8 | 2-Hydroxymethyl-Pyrrolidine-3,4-Diol | Drug Info | [14] | |||
| 9 | 3-((2-Pyrrolidine-1-yl)-ethyl)uracil | Drug Info | [15] | |||
| 10 | 3-Deoxyguanosine | Drug Info | [6] | |||
| 11 | 5'-deoxy-4'-hydroxy-5'-methylthio-DADMe-ImmH | Drug Info | [13] | |||
| 12 | 5'-Methylthio-ImmH | Drug Info | [13] | |||
| 13 | 5'-methylthio-immucillin-H | Drug Info | [15] | |||
| 14 | 5'-phenylthio-ImmH | Drug Info | [13] | |||
| 15 | 7-tert-butyl-2, 3-dihydro-3, 3-dimethyl substituted dihydrofuran 30 (DHDMBF30) | Drug Info | [16] | |||
| 16 | 8-amino-9-benzylguanine | Drug Info | [16] | |||
| 17 | 8-AMINOGUANINE | Drug Info | [17] | |||
| 18 | 8-aminoguanosine | Drug Info | [18] | |||
| 19 | 8-aza-DADMe-ImmH | Drug Info | [19] | |||
| 20 | 8-Azaguanine | Drug Info | [6] | |||
| 21 | 8-Iodo-Guanine | Drug Info | [6] | |||
| 22 | 9-(5,5-Difluoro-5-Phosphonopentyl)Guanine | Drug Info | [6], [20] | |||
| 23 | 9-Deazahypoxanthine | Drug Info | [6] | |||
| 24 | 9-Deazainosine | Drug Info | [6] | |||
| 25 | 9-DEAZAINOSINE-2',3'-O-ETHYLIDENEPHOSPHONATE | Drug Info | [21] | |||
| 26 | Aza-C-nucleosides | Drug Info | [22] | |||
| 27 | DADMe-ImmG | Drug Info | [19] | |||
| 28 | GUANOSINE-2',3'-O-ETHYLIDENEPHOSPHONATE | Drug Info | [21] | |||
| 29 | GUANOSINE-2',3'-O-METHYLIDENEPHOSPHONATE | Drug Info | [21] | |||
| 30 | Hypoxanthine | Drug Info | [6] | |||
| 31 | Immucillin-G | Drug Info | [22] | |||
| 32 | MT-Immucillin-H | Drug Info | [23] | |||
| 33 | Ribose-1-Phosphate | Drug Info | [6] | |||
| 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 Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | BCX-4208 (RO5092888), a Purine Nucleoside Phosphorylase (PNP) Inhibitor, Is a Novel, Potent Orally Active Anti-T-Cell and B-Cell Agent. 50th ASH Annual Meeting and Exposition. 2008. | |||||
| REF 2 | ClinicalTrials.gov (NCT01407874) A Randomized, Double-Blind, Dose-Response Study of the Safety and Uric Acid Effects of Oral Ulodesine Added to Allopurinol in Subjects With Gout and Concomitant Moderate Renal Insufficiency. U.S. National Institutes of Health. | |||||
| REF 3 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8272). | |||||
| REF 4 | Emerging drugs in cutaneous T cell lymphoma. Expert Opin Emerg Drugs. 2008 Jun;13(2):345-61. | |||||
| REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002367) | |||||
| REF 6 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 7 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 8 | Azetidine based transition state analogue inhibitors of N-ribosyl hydrolases and phosphorylases. J Med Chem. 2008 Feb 28;51(4):948-56. | |||||
| REF 9 | Forodesine has high antitumor activity in chronic lymphocytic leukemia and activates p53-independent mitochondrial apoptosis by induction of p73 an... Blood. 2009 Aug 20;114(8):1563-75. | |||||
| REF 10 | Synthesis of analogs of forodesine HCl, a human purine nucleoside phosphorylase inhibitor-Part I. Bioorg Med Chem Lett. 2009 May 15;19(10):2624-6. | |||||
| REF 11 | Novel therapies for cutaneous T-cell lymphomas. Clin Lymphoma Myeloma. 2008 Dec;8 Suppl 5:S187-92. | |||||
| REF 12 | Inhibitors of human purine nucleoside phosphorylase. Synthesis of pyrrolo[3,2-d]pyrimidines, a new class of purine nucleoside phosphorylase inhibitors as potentially T-cell selective immunosuppressive agents. Description of 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d] pyrimidin-4-one. J Med Chem. 1992 May 1;35(9):1605-9. | |||||
| REF 13 | Immucillins in custom catalytic-site cavities. Bioorg Med Chem Lett. 2008 Nov 15;18(22):5900-3. | |||||
| REF 14 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 15 | Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase. Eur J Med Chem. 2010 Nov;45(11):5140-9. | |||||
| REF 16 | Expression of human malaria parasite purine nucleoside phosphorylase in host enzyme-deficient erythrocyte culture. Enzyme characterization and identification of novel inhibitors. J Biol Chem. 1986 Sep 5;261(25):11667-73. | |||||
| REF 17 | Nucleosides. 5. Synthesis of guanine and formycin B derivatives as potential inhibitors of purine nucleoside phosphorylase. J Med Chem. 1993 Apr 16;36(8):1024-31. | |||||
| REF 18 | Differential metabolism of guanine nucleosides by human lymphoid cell lines. Proc Soc Exp Biol Med. 1985 Sep;179(4):427-31. | |||||
| REF 19 | Achieving the ultimate physiological goal in transition state analogue inhibitors for purine nucleoside phosphorylase. J Biol Chem. 2003 Aug 22;278(34):31465-8. | |||||
| REF 20 | Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mamma... Bioorg Med Chem. 2010 Mar 15;18(6):2275-2284. | |||||
| REF 21 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 22 | Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase. J Med Chem. 2003 Jul 17;46(15):3412-23. | |||||
| REF 23 | Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function. J Biol Chem. 2004 Apr 30;279(18):18103-6. | |||||
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