Drug Information

Drug (ID: DG00860) and It's Reported Resistant Information

• Name: Azacitidine
• Synonyms: 5-azacytidine; Azacitidine; 320-67-2; Ladakamycin; Azacytidine; Vidaza; Mylosar; 5-azacitidine; Azacitidinum; Azacitidina; Azacitidinum [INN-Latin]; 5-AZAC; Azacitidina [INN-Spanish]; NSC-102816; C8H12N4O5; NSC 102816; U-18496; 4-Amino-1-beta-D-ribofuranosyl-s-triazin-2(1H)-one; UNII-M801H13NRU; NSC102816; 5AzaC; 4-Amino-1-beta-d-ribofuranosyl-1,3,5-triazin-2(1H)-one; Antibiotic U 18496; CHEBI:2038; M801H13NRU; 4-amino-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1,3,5-triazin-2(1H)-one; 4-Amino-1-(beta-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one; MFCD00006539; 4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one; 4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydro-1,3,5-triazin-2-one; WR-183027; NCGC00090851-04; DSSTox_CID_116; U 18496; DSSTox_RID_75378; DSSTox_GSID_20116; U-18,496; CCRIS 60; SMR000857239; Vidaza (TN); HSDB 6879; 5-aza-CR; SR-01000075662; EINECS 206-280-2; BRN 0620461; Onureg; Azacitidine (JAN/USAN/INN); Azacitidine [USAN:INN:BAN]; 4-Amino-1-beta-D-ribofuranosyl-1,3,5-traizin-2(1H)-one; NS-17; 4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1,3,5-triazin-2-one; CAS-320-67-2; Azacitidine (Vidaza); 2-(beta-D-Ribofuranosyl)-4-amino-1,3,5-triazin-2-one; Antibiotic U18496; U18496; Spectrum_001262; 4-Amino-1-beta-D-ribofuranosyl-1,3,5-triazine-2(1H)-one; Spectrum2_000786; Spectrum3_001509; Spectrum4_000922; Spectrum5_001166; MolMap_000062; A 2385; SCHEMBL3741; CHEMBL1489; Azacitidine (5-Azacytidine); Lopac0_000035; BSPBio_003157; KBioGR_001444; KBioGR_002556; KBioSS_001742; KBioSS_002565; MLS001333121; MLS001333122; MLS002153249; MLS002548894; DivK1c_000125; SPECTRUM1502111; SPBio_000892; GTPL6796; DTXSID9020116; BCBcMAP01_000083; HMS500G07; KBio1_000125; KBio2_001742; KBio2_002556; KBio2_004310; KBio2_005124; KBio2_006878; KBio2_007692; KBio3_002657; KBio3_003034; NMUSYJAQQFHJEW-KVTDHHQDSA-; pyrimidine antimetabolite: inhibits nucleic acid replication; cMAP_000082; NINDS_000125; HMS1921J22; HMS2092D08; HMS2231F15; HMS3259D19; HMS3260G11; Pharmakon1600-01502111; ZINC3861768; 5-Azacytidine, >=98% (HPLC); Tox21_111032; Tox21_302985; Tox21_500035; BDBM50424715; CCG-39046; NSC758186; s1782; Onureg (CC-486; oral azacitidine); AKOS015896938; Tox21_111032_1; AM83944; CS-1287; DB00928; LP00035; MCULE-8318770472; NC00672; NSC-758186; NSC103-627; 4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triaz; IDI1_000125; NCGC00090851-01; NCGC00090851-02; NCGC00090851-03; NCGC00090851-05; NCGC00090851-06; NCGC00090851-07; NCGC00090851-08; NCGC00090851-10; NCGC00090851-14; NCGC00090851-22; NCGC00178234-01; NCGC00256541-01; NCGC00260720-01; AS-13697; HY-10586; SRI-10756_10; SRI-10756_12; WR183027; DB-006955; SL-000003; EU-0100035; D03021; F10504; J10124; 320A672; A821115; Q416451; J-700085; SR-01000075662-1; SR-01000075662-3; SR-01000075662-7; BRD-K03406345-001-02-1; BRD-K03406345-001-27-8; 4-Amino-1- -D-ribofuranosyl-1,3,5-triazin-2(1H)-one; Z1522566611; 4-Amino-1-(bet.-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one; 4-Amino-1-beta-D-ribofuranosyl-1,3,5-tr iazin-2(1H)-one; s-Triazin-2(1H)-one, 4-amino-1-beta-D-ribofuranosyl- (8CI); Azacitidine, United States Pharmacopeia (USP) Reference Standard; 4-Amino-1-(beta-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one; Ladakamycin; Azacitidine, Pharmaceutical Secondary Standard; Certified Reference Material; 1401238-97-8; 5-Azacytidine, Hybri-Max(TM), gamma-irradiated, lyophilized powder, BioXtra, suitable for hybridoma; 5AE; 6-amino-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-1,3,5-triazin-3-ium-2-one
• Indication:
  In total 2 Indication(s)
  Myelodysplastic syndrome [ICD-11: 2A37]; Approved; [1]
  Myelodysplastic syndrome [ICD-11: 2A37]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Myelodysplastic syndrome [ICD-11: 2A37]; [1]
• Target: DNA [cytosine-5]-methyltransferase (DNMT); NOUNIPROTAC; [1]
• Formula: C8H12N4O5
• IsoSMILES: C1=NC(=NC(=O)N1[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)O)N
• InChI: 1S/C8H12N4O5/c9-7-10-2-12(8(16)11-7)6-5(15)4(14)3(1-13)17-6/h2-6,13-15H,1H2,(H2,9,11,16)/t3-,4-,5-,6-/m1/s1
• InChIKey: NMUSYJAQQFHJEW-KVTDHHQDSA-N
• PubChem CID: 9444
• ChEBI ID: CHEBI:2038
• TTD Drug ID: D09FAZ
• VARIDT ID: DR00983
• INTEDE ID: DR0163
• DrugBank ID: DB00928

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [2]

• Sensitive Disease: FGFR-tacc positive glioblastoma [ICD-11: 2A00.01]
• Molecule Alteration: Missense mutation; p.R132H (c.395G>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.65 Å; PDB: 6BKX
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 1.88 Å; PDB: 4UMX

RMSD: 3.46; TM score: 0.85834; Amino acid change: R132H

• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Brain; N.A.
• In Vivo Model: Female athymic nude mouse (NCI-Frederick) model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume measurement assay

Myelodysplastic syndrome [ICD-11: 2A37]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Lysosome-associated membrane glycoprotein 2 (LAMP2) [1]

• Resistant Disease: Myelodysplastic syndrome [ICD-11: 2A37.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Mechanism Description: We show that treatment of MDS/AML cell lines and bone marrow samples from MDS/AML patients with Aza triggers loss of LAMP2 expression leading to CMA defects. LAMP2 deficiency is responsible for CMA defects, Aza resistance and hypersensitivity to lysosome and autophagy inhibitors. Low levels of LAMP2 expression in CD34+ blasts from MDS/AML patients correlate with an absence of response to Aza and are associated to a pejorative overall survival. We propose that CD34+/LAMP2Low patients at diagnosis or who become CD34+/LAMP2Low during the course of treatment with Aza could receive an autophagy inhibitor available in the clinic.

References

• Ref 1: Azacitidine resistance caused by LAMP2 deficiency: a therapeutic window for the use of autophagy inhibitors in MDS/AML patients .Autophagy. 2019 May;15(5):927-929. doi: 10.1080/15548627.2019.1586259. Epub 2019 Mar 1. 10.1080/15548627.2019.1586259
• Ref 2: 5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograftOncotarget. 2013 Oct;4(10):1737-47. doi: 10.18632/oncotarget.1408.