Drug Details

General Information of the Drug (ID: DR2370)
Name
Azacitidine
Synonyms
Azacitidina; Azacitidinum; Azacytidine; Ladakamycin; Mylosar; Vidaza; Mylo sar; Pharmion Brand of Azacitidine; A 2385; Antibiotic U 18496; U 18496; Wr 183027; Azacitidina [INN-Spanish]; Azacitidine [USAN:INN]; Azacitidinum [INN-Latin]; NS-17; Pyrimidine antimetabolite: inhibits nucleic acid replication; U-18496; Vidaz (TN); Vidaza (TN); WR-183027; Azacitidine (JAN/USAN/INN); S-Triazin-2(1H)-one, 4-amino-1-beta-D-ribofuranosyl-(8CI); 2-(beta-D-Ribofuranosyl)-4-amino-1,3,5-triazin-2-one; 4-Amino-1-(beta-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one; 4-Amino-1-beta-D-ribofuranosyl-1,3,5-traizin-2(1H)-one; 4-Amino-1-beta-D-ribofuranosyl-1,3,5-triazine-2(1H)-one; 4-Amino-1-beta-D-ribofuranosyl-s-triazin-2(1H)-one; 4-Amino-1-beta-d-ribofuranosyl-1,3,5-triazin-2(1H)-one; 4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triaz; 4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one; 4-amino-1-beta-L-ribofuranosyl-1,3,5-triazin-2(1H)-one; 5 AZC; 5 Azacytidine; 5-AC; 5-AZAC; 5-AZCR; 5-aza-CR; 5-azacitidine; 5-azacytidine; 5-azacytidine, Mylosar, Ladakamycin, Vidaza, Azacitidine; 5AzaC
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Molecular Type
Small molecule
Disease Myelodysplastic syndrome [ICD-11: 2A37] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability
Clearance
The clearance of drug is 167 +/- 49 L/h
Elimination
62% of drug is excreted from urine in the unchanged form
Half-life
The concentration or amount of drug in body reduced by one-half in 4 hours
Metabolism
The drug is metabolized via the liver
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 177.10271 micromolar/kg/day
Vd
The volume of distribution (Vd) of drug is 76 +/- 26 L
Water Solubility
The ability of drug to dissolve in water is measured as 89 mg/mL
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Formula
C8H12N4O5
PubChem CID
9444
Canonical SMILES
C1=NC(=NC(=O)N1C2C(C(C(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
CAS Number
CAS 320-67-2
ChEBI ID
CHEBI:2038
TTD Drug ID
D09FAZ
DrugBank ID
DB00928
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Arsenic trioxide      Realgar and orpiment     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression XAF1  Molecule Info 
Pathway MAP
                    In-vitro Model 8226 CVCL_0014 Plasma cell myeloma Homo sapiens
XG-7 CVCL_A772 Plasma cell myeloma Homo sapiens
                    Experimental
                    Result(s)		 Combination of DNA methylation inhibitor 5-azacytidine and arsenic trioxide has synergistic activity in myeloma.
          Curcumin      Hellenia speciosa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model HL-60 CVCL_0002 Adult acute myeloid leukemia Homo sapiens
U-937 CVCL_0007 Adult acute monocytic leukemia Homo sapiens
K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
OCI-AML-3 CVCL_1844 Adult acute myeloid leukemia Homo sapiens
                    Experimental
                    Result(s)		 Combination of Azacitidine and curcumin showed a synergy in all leukemic lines and in most leukemic samples, with a decrease in proliferation and an increase in apoptosis compared to the activity of each drug separately. Azacitidine plus curcumin showed low cytotoxicity in healthy samples.
Target and Pathway
Target(s) DNA [cytosine-5]-methyltransferase (DNMT)  Molecule Info  [4]
References
Reference 1 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: 6796).
Reference 2 Combination of DNA methylation inhibitor 5-azacytidine and arsenic trioxide has synergistic activity in myeloma. Eur J Haematol. 2009 Mar;82(3):176-83.
Reference 3 Synergistic Antioncogenic Activity of Azacitidine and Curcumin in Myeloid Leukemia Cell Lines and Patient Samples. Anticancer Res. 2019 Sep;39(9):4757-4766.
Reference 4 The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid l... Leukemia. 2009 Jun;23(6):1019-28.
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