Drug Information

Drug (ID: DG01312) and It's Reported Resistant Information

• Name: Allopurinol
• Synonyms: Allopurinol; 315-30-0; 1H-Pyrazolo[3,4-d]pyrimidin-4-ol; Zyloprim; Zyloric; Lopurin; Atisuril; Bleminol; Caplenal; Suspendol; Uripurinol; Embarin; Foligan; Milurit; Progout; Urosin; Anoprolin; Cellidrin; Epidropal; Takanarumin; Ailural; Allopur; Allural; Alositol; Bloxanth; Cosuric; Hamarin; Ledopur; Lysuron; Uricemil; Uriprim; Xanturat; Aloral; Anzief; Apurin; Apurol; Geapur; Gotax; Remid; Urbol; Urolit; Urtias; Ketobun-A; Apulonga; Dabrosin; Dabroson; Ketanrift; Miniplanor; Nektrohan; Urobenyl; Adenock; Allozym; Aluline; Gichtex; Monarch; Riball; 4-Hydroxypyrazolo[3,4-d]pyrimidine; Hexanuret; Epuric; 1H-Pyrazolo[3,4-d]pyrimidin-4(5H)-one; Allo-Puren; 4-HPP; Allopurinol(I); Dura Al; Allopurinolum; Aloprim; Urtias 100; 4-Hydroxypyrazolopyrimidine; 1H-Pyrazolo(3,4-d)pyrimidin-4-ol; 4-Hydroxy-1H-pyrazolo(3,4-d)pyrimidine; Alopurinol; 4-Hydroxy-3,4-pyrazolopyrimidine; 4-Hydroxypyrazolo(3,4-d)pyrimidine; Alopurinol [INN-Spanish]; Allopurinolum [INN-Latin]; 180749-08-0; NSC-1390; 180749-06-8; 1H-pyrazolo[3,4-d]pyrimidin-4(7H)-one; 4-Hydroxypyrazolyl(3,4-d)pyrimidine; 4H-Pyrazolo(3,4-d)pyrimidin-4-one; 4'-Hydroxypyrazolol(3,4-d)pyrimidine; AL-100; BW 56-158; Zyloprim (TN); 73334-58-4; 1,5-Dihydro-4H-pyrazolo(3,4-d)pyrimidin-4-one; 2H-Pyrazolo[3,4-d]pyrimidin-4-ol; 4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1,5-dihydro-; B. W. 56-158; 1,5-Dihydro-4H-pyrazolo(3,4-d)pyrimidine-4-one; BW-56-158; UNII-63CZ7GJN5I; 180749-09-1; 1,5-Dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one; MLS000069453; 4H-Pyrazolo(3,4-d)pyrimidin-4-one, 1,5-dihydro-; CHEBI:40279; 1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one; MFCD00599413; 180749-07-9; 184789-03-5; 63CZ7GJN5I; SMR000059083; 4-Hydroxy-1H-pyrazolo[3,4-d]pyrimidine; 1H-Pyrazolo[3,4-d]pyrimidin-4-ol (9CI); 4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1,7-dihydro- (9CI); 1,5-Dihydropyrazolo[3,4-d]pyrimidin-4-one; 1H,4H,5H-pyrazolo[3,4-d]pyrimidin-4-one; NSC1390; 4H-Pyrazolo[3,4-d]pyrimidin-4-one, 1,2-dihydro-; NSC101655; NSC-101655; NCGC00015094-02; NCGC00094580-04; 4H-Pyrazolo[3,4-d]pyrimidin-4-one, 2,5-dihydro- (9CI); 4H-Pyrazolo[3,4-d]pyrimidin-4-one, 2,7-dihydro- (9CI); BW 56158; BW-56158; Sigapurol; Uritas; 1H,2H,4H-pyrazolo[3,4-d]pyrimidin-4-one; DSSTox_CID_2573; 1,5-Dihydro-pyrazolo[3,4-d]pyrimidin-4-one; DSSTox_RID_76636; DSSTox_GSID_22573; 4H-Pyrazolo[3, 1,5-dihydro-; Ailurial; WLN: T56 BMN GN INJ FQ; 4-Hydroxypyrazolyl[3,4-d]pyrimidine; 4'-Hydroxypyrazolol[3,4-d]pyrimidine; NSC 1390; CAS-315-30-0; CCRIS 626; NSC 101655; HSDB 3004; SR-05000001983; EINECS 206-250-9; Hexanurat; Uricto; ATH008; Xanthine oxidase; Prestwick_511; Xanthomax-100; Xanthomax-300; 4H-Pyrazolo[3,4-d]pyrimidin-4-one,1,2-dihydro-; Aluline 100; Aluline 300; Hamarin 100; Hamarin 300; Zyloric-300; Allopurinol [USAN:USP:INN:BAN:JAN]; Allopurinol (Zyloprim); Spectrum_000026; Opera_ID_1680; Spectrum2_000098; Spectrum3_000289; Spectrum4_000135; Spectrum5_000768; Lopac-A-8003; 1,4-d]pyrimidin-4-one; A 8003; cid_2094; SCHEMBL4627; CHEMBL1467; NCIOpen2_001825; Lopac0_000102; BSPBio_001798; KBioGR_000550; KBioSS_000386; MLS001148183; US9138393, Allopurinol; US9144538, Allopurinol; DivK1c_000685; SPECTRUM1500108; SPBio_000056; GTPL6795; SCHEMBL1128219; Allopurinol (JP17/USP/INN); DTXSID4022573; BDBM35440; HMS502C07; KBio1_000685; KBio2_000386; KBio2_002954; KBio2_005522; KBio3_001298; NINDS_000685; BDBM181133; HMS1920A15; HMS2091G15; HMS2234M09; HMS3259K13; HMS3260E06; HMS3371I11; HMS3651O13; HMS3714L22; Pharmakon1600-01500108; 4-Hydroxypyrazol[3,4-D]pyrimidine; ACT02732; AMY18272; BCP26973; HY-B0219; STR05189; Tox21_110082; Tox21_200922; Tox21_500102; 2204AH; 4-Hydroxy-pyrazolo[3,4-d]pyrimidin; AC-019; BBL009959; BDBM50016784; BDBM50140241; CCG-38916; NSC755858; s1630; SC1118; SC2251; STK378584; STK711106; ZINC13298313; AKOS000267490; AKOS000269759; AKOS024255717; Tox21_110082_1; Allopurinol, xanthine oxidase inhibitor; CCG-204197; CCG-221406; CCG-266128; DB00437; LP00102; MCULE-5186178136; NC00492; NSC-755858; SB10164; SDCCGSBI-0050090.P005; IDI1_000685; NCGC00015094-01; NCGC00015094-03; NCGC00015094-04; NCGC00015094-05; NCGC00015094-06; NCGC00015094-07; NCGC00015094-08; NCGC00015094-22; NCGC00091134-01; NCGC00091134-02; NCGC00091134-03; NCGC00094580-01; NCGC00094580-02; NCGC00094580-05; NCGC00188948-01; NCGC00258476-01; NCGC00260787-01; 291279-53-3; TS-00028; 2h-pyrazolo[3,4-d]pyrimidin-4(5h)-one; 2H-pyrazolo[3,4-d]pyrimidin-4(7H)-one; SBI-0050090.P004; DB-065332; 2H-Pyrazolo[3,4-d]pyrimidin-4-ol (9CI); A0907; EU-0100102; FT-0602537; FT-0661492; FT-0685730; FT-0764079; SW199406-4; 1,5-dihydropyrazolo[3,4-d]-pyrimidin-4-one; VU0611037-1; BIM-0061756.0001; D00224; F18007; AB00173448-03; AB00173448-04; AB00173448_05; AB01274719-01; AB01274719_02; 4h-pyrazolo[3,4-d]pyrimidin-4-one,1,7-dihydro-; 4h-pyrazolo[3,4-d]pyrimidin-4-one,2,5-dihydro-; 4h-pyrazolo[3,4-d]pyrimidin-4-one,2,7-dihydro-; AB-323/25048497; Allopurinol (4-Hydroxypyrazolo[3,4-d]pyrimidine); Q412486; SR-01000075595; 4H-pyrazolo[3,4-d]pyrimidin-4-one, 1,7-dihydro-; J-504736; SR-01000075595-1; SR-05000001983-1; SR-05000001983-2; W-106892; 1,2-DIHYDRO-4H-PYRAZOLO[3,4-D]PYRIMIDIN-4-ONE; 1,5-Dihydro-4H-pyrazolo(3,4-d)pyrimidin-4-one (9CI); F2173-0394; F3329-0375; Z228474686; Allopurinol, British Pharmacopoeia (BP) Reference Standard; Allopurinol, European Pharmacopoeia (EP) Reference Standard; Allopurinol, United States Pharmacopeia (USP) Reference Standard; 1,5-Dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one Synonym: Allopurinol; Allopurinol, Pharmaceutical Secondary Standard; Certified Reference Material; 1H-Pyrazolo[3,4-d]pyrimidin-4-ol;1H-PYRAZOLO[3,4-D]PYRIMIDIN-4(5H)-ONE; 9002-17-9
• Indication:
  In total 1 Indication(s)
  Hyperuricaemia [ICD-11: 5C55]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Leishmaniasis [ICD-11: 1F54]; [1]
• Target: Xanthine dehydrogenase/oxidase (XDH); XDH_HUMAN; [1]
• Formula: C5H4N4O
• IsoSMILES: C1=NNC2=C1C(=O)NC=N2
• InChI: 1S/C5H4N4O/c10-5-3-1-8-9-4(3)6-2-7-5/h1-2H,(H2,6,7,8,9,10)
• InChIKey: OFCNXPDARWKPPY-UHFFFAOYSA-N
• PubChem CID: 135401907
• ChEBI ID: CHEBI:40279
• TTD Drug ID: D04KYY
• VARIDT ID: DR00074
• INTEDE ID: DR0066
• DrugBank ID: DB00437

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Leishmaniasis [ICD-11: 1F54]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: S-adenosylmethionine synthase (METK) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Visceral leishmaniasis [ICD-11: 1F54.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Leishmania infantum strain; 5671
• Experiment for Molecule Alteration: Quantitative PCR assays
• Mechanism Description: A reduction in copy number for LinJ.30.3560, encoding the S-adenosylmethionine synthetase (METK) gene, was found in two resistant clinical isolates and four induced resistant clonal strains. Using quantitative real time PCR, this reduction in METK copy number was also found in three additional resistant clinical isolates. Since allopurinol can be incorporated into energetic nucleotides such as ATP it may be that such allopurinol containing nucleotides inhibit S-adenosylmethionine synthetase or are utilized by it, producing faulty products, which in turn inhibit the parasite's growth. Down-regulation of S-adenosylmethionine synthetase in resistant strains may reduce the levels of such faulty products.

References

• Ref 1: Resistance of Leishmania infantum to allopurinol is associated with chromosome and gene copy number variations including decrease in the S-adenosylmethionine synthetase (METK) gene copy number .Int J Parasitol Drugs Drug Resist. 2018 Dec;8(3):403-410. doi: 10.1016/j.ijpddr.2018.08.002. Epub 2018 Aug 23. 10.1016/j.ijpddr.2018.08.002