Target Information

Target General Infomation
Target ID
T78198
Former ID
TTDC00091
Target Name
Purine nucleoside phosphorylase
Gene Name
PNP
Synonyms
Inosine phosphorylase; Purine-nucleoside phosphorylase; PNP
Target Type
Clinical Trial
Disease Autoimmune diabetes [ICD10: E08-E13]
Gout; Moderate-to-severe plaque psoriasis [ICD9:274.00274.1274.8274.9, 696; ICD10: M10, L40]
Refractory cutaneous T-cell lymphoma; B-cell acute lymphoblastic leukemia [ICD9: 202.1, 202.2, 202.8, 204.0, 208.9; ICD10: C81-C86, C84.0, C84.1, C91-C95, C91.0]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
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.
BioChemical Class
Pentosyltransferase
Target Validation
T78198
UniProt ID
P00491
EC Number
EC 2.4.2.1
Sequence
MENGYTYEDYKNTAEWLLSHTKHRPQVAIICGSGLGGLTDKLTQAQIFDYGEIPNFPRST
VPGHAGRLVFGFLNGRACVMMQGRFHMYEGYPLWKVTFPVRVFHLLGVDTLVVTNAAGGL
NPKFEVGDIMLIRDHINLPGFSGQNPLRGPNDERFGDRFPAMSDAYDRTMRQRALSTWKQ
MGEQRELQEGTYVMVAGPSFETVAECRVLQKLGADAVGMSTVPEVIVARHCGLRVFGFSL
ITNKVIMDYESLEKANHEEVLAAGKQAAQKLEQFVSILMASIPLPDKAS
Structure
1M73; 1PF7; 1PWY; 1RCT; 1RFG; 1RR6; 1RSZ; 1RT9; 1ULA; 1ULB; 1V2H; 1V3Q; 1V41; 1V45; 1YRY; 2A0W; 2A0X; 2A0Y; 2OC4; 2OC9; 2ON6; 2Q7O; 3BGS; 3D1V; 3GB9; 3GGS; 3INY; 3K8O; 3K8Q; 3PHB; 4EAR; 4EB8; 4ECE; 4GKA
Drugs and Mode of Action
Drug(s) 2'3'-Dideoxyinosine Drug Info Phase 2 Discovery agent [521413]
BCX-3408 Drug Info Phase 2 Discovery agent [522068]
BCX-4208 Drug Info Phase 2 Gout; Moderate-to-severe plaque psoriasis [523572]
Ulodesine Drug Info Phase 2 Autoimmune diabetes [523572]
Forodesine Drug Info Phase 1/2 Refractory cutaneous T-cell lymphoma; B-cell acute lymphoblastic leukemia [536739], [543027]
Guanosine Drug Info Phase 1 Discovery agent [467804], [523731]
Peldesine Drug Info Phase 1 Discovery agent [521434]
CI-972 Drug Info Discontinued in Phase 1 Rheumatoid arthritis [545178]
Inhibitor (+/-)-5'-deoxy-4'-fluoro-5'-methylthio-DADMe-ImmH Drug Info [529677]
2'3'-Dideoxyinosine Drug Info [551393]
2,8-Diamino-9-benzyl-1,9-dihydro-purin-6-one Drug Info [534048]
2-Hydroxymethyl-Pyrrolidine-3,4-Diol Drug Info [551391]
3-((2-Pyrrolidine-1-yl)-ethyl)uracil Drug Info [531149]
3-Deoxyguanosine Drug Info [551393]
5'-deoxy-4'-hydroxy-5'-methylthio-DADMe-ImmH Drug Info [529677]
5'-Methylthio-ImmH Drug Info [529677]
5'-methylthio-immucillin-H Drug Info [531149]
5'-phenylthio-ImmH Drug Info [529677]
8-amino-5'-deoxy-5'-chloroguanosine Drug Info [537731]
8-amino-9-benzylguanine Drug Info [537731]
8-AMINOGUANINE Drug Info [534048]
8-aminoguanosine Drug Info [537760]
8-aza-DADMe-ImmH Drug Info [535759]
8-Azaguanine Drug Info [551393]
8-Iodo-Guanine Drug Info [551393]
9-(5',5'-difluoro-5'-phosphonopentyl)guanine Drug Info [530755]
9-(5,5-Difluoro-5-Phosphonopentyl)Guanine Drug Info [551393]
9-Deazahypoxanthine Drug Info [551393]
9-Deazainosine Drug Info [551393]
9-DEAZAINOSINE-2',3'-O-ETHYLIDENEPHOSPHONATE Drug Info [551374]
Aza-C-nucleosides Drug Info [535761]
BCX-3408 Drug Info [529290]
BCX-4208 Drug Info [549732]
CI-972 Drug Info [536061]
DADMe-ImmG Drug Info [535759]
DADMe-ImmH Drug Info [535759]
Forodesine Drug Info [536974], [537256], [537497]
Guanosine Drug Info [551393]
GUANOSINE-2',3'-O-ETHYLIDENEPHOSPHONATE Drug Info [551374]
GUANOSINE-2',3'-O-METHYLIDENEPHOSPHONATE Drug Info [551374]
Hypoxanthine Drug Info [551393]
Immucillin-G Drug Info [535761]
MT-Immucillin-H Drug Info [551399]
Peldesine Drug Info [551393]
Ribose-1-Phosphate Drug Info [551393]
Ulodesine Drug Info [1572591]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Arsenate detoxification I (glutaredoxin)
Purine nucleotides degradation
Urate biosynthesis/inosine 5&#039
-phosphate degradation
Purine deoxyribonucleosides degradation
Purine ribonucleosides degradation to ribose-1-phosphate
Guanosine nucleotides degradation
Adenosine nucleotides degradation
Superpathway of purine nucleotide salvage
Adenine and adenosine salvage III
Guanine and guanosine salvage
KEGG Pathway Purine metabolism
Pyrimidine metabolism
Nicotinate and nicotinamide metabolism
Metabolic pathways
NetPath Pathway TCR Signaling Pathway
EGFR1 Signaling Pathway
PANTHER Pathway Adenine and hypoxanthine salvage pathway
Xanthine and guanine salvage pathway
PathWhiz Pathway Purine Metabolism
Nicotinate and Nicotinamide Metabolism
Reactome Purine salvage
Purine catabolism
WikiPathways miR-targeted genes in squamous cell - TarBase
miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in epithelium - TarBase
Metabolism of nucleotides
References
Ref 467804(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: 4567).
Ref 521413ClinicalTrials.gov (NCT00000657) Comparison of 2',3'-Dideoxyinosine (Didanosine, ddI) and Zidovudine in Therapy of Patients With the AIDS Dementia Complex. U.S. National Institutes of Health.
Ref 521434ClinicalTrials.gov (NCT00002237) A Study of Peldesine (BCX-34) in HIV-Infected Patients. U.S. National Institutes of Health.
Ref 522068ClinicalTrials.gov (NCT00504270) A Study of R3421 in Patients With Moderate to Severe Chronic Plaque Psoriasis.. U.S. National Institutes of Health.
Ref 523572ClinicalTrials.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 523731ClinicalTrials.gov (NCT01493570) Assessment of Exposure of BI 409306 in Cerebrospinal Fluid (CSF) Relative to Plasma as Well as to Evaluation of the Effect of Different Doses of BI 409306 on the cGMP(Cyclic Guanosine Monophosphate) Levels in CSF in Healthy Male Volunteers. U.S. National Institutes of Health.
Ref 536739Emerging drugs in cutaneous T cell lymphoma. Expert Opin Emerg Drugs. 2008 Jun;13(2):345-61.
Ref 543027(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 545178Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002367)
Ref
Ref 529290J Med Chem. 2008 Feb 28;51(4):948-56. Epub 2008 Feb 6.Azetidine based transition state analogue inhibitors of N-ribosyl hydrolases and phosphorylases.
Ref 529677Bioorg Med Chem Lett. 2008 Nov 15;18(22):5900-3. Epub 2008 Aug 19.Immucillins in custom catalytic-site cavities.
Ref 530755Bioorg Med Chem. 2010 Mar 15;18(6):2275-84. Epub 2010 Feb 4.Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mammalian PNPs.
Ref 531149Eur J Med Chem. 2010 Nov;45(11):5140-9. Epub 2010 Aug 14.Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase.
Ref 534048J Med Chem. 1993 Apr 16;36(8):1024-31.Nucleosides. 5. Synthesis of guanine and formycin B derivatives as potential inhibitors of purine nucleoside phosphorylase.
Ref 535759Achieving the ultimate physiological goal in transition state analogue inhibitors for purine nucleoside phosphorylase. J Biol Chem. 2003 Aug 22;278(34):31465-8. Epub 2003 Jul 3.
Ref 535761Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase. J Med Chem. 2003 Jul 17;46(15):3412-23.
Ref 536061Inhibitors 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 536974Novel therapies for cutaneous T-cell lymphomas. Clin Lymphoma Myeloma. 2008 Dec;8 Suppl 5:S187-92.
Ref 537256Synthesis of analogs of forodesine HCl, a human purine nucleoside phosphorylase inhibitor-Part I. Bioorg Med Chem Lett. 2009 May 15;19(10):2624-6. Epub 2009 Apr 9.
Ref 537497Forodesine has high anti-tumor activity in chronic lymphocytic leukemia and activates p53-independent mitochondrial apoptosis via induction of p73 and BIM. Blood. 2009 Jun 18.
Ref 537731Expression 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 537760Differential metabolism of guanine nucleosides by human lymphoid cell lines. Proc Soc Exp Biol Med. 1985 Sep;179(4):427-31.
Ref 549732BCX-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 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551391DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-4. Nucleic Acids Res. 2011 January
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551399Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function. J Biol Chem. 2004 Apr 30;279(18):18103-6. Epub 2004 Feb 23.
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.