Azacitidine

Identification

Summary

Azacitidine is a pyrimidine nucleoside analogue used to treat certain subtypes of myelodysplastic syndrome.

Brand Names
Onureg, Vidaza
Generic Name
Azacitidine
DrugBank Accession Number
DB00928
Background

Azacitidine is a pyrimidine nucleoside analogue with anti-neoplastic activity. It differs from cytosine by the presence of nitrogen in the C5-position, key in its hypomethylating activity.1,8,10 Two main mechanisms of action have been proposed for azacitidine. One of them is the induction of cytotoxicity. As an analogue of cytidine, it is able to incorporate into RNA and DNA, disrupting RNA metabolism and inhibiting protein and DNA synthesis. The other one is through the inhibition of DNA methyltransferase, impairing DNA methylation.2 Due to its anti-neoplastic activity and its ability to inhibit methylation in replicating DNA, azacytidine has been used mainly used in the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), two types of cancer characterized by the presence of aberrant DNA methylation.2,5,6,11,12

In May 2004, the FDA approved the use of azacitidine administered subcutaneously for the treatment of MDS of all French-American-British (FAB) subtypes. In January 2007, the FDA approved the intravenous administration of azacitidine.10 The use of oral azacitidine for the treatment of AML in patients in complete remission was approved by the FDA in September 2020.13

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 244.2047
Monoisotopic: 244.080769514
Chemical Formula
C8H12N4O5
Synonyms
  • 4-amino-1-beta-D-ribofuranosyl-s-triazin-2(1H)-one
  • 5-azacytidine
  • Azacitidina
  • Azacitidine
  • Azacitidinum
  • Azacytidine
External IDs
  • CC-486
  • NSC-102816
  • U-18,496
  • U-18496

Pharmacology

Indication

Azacitidine (for subcutaneous or intravenous use) is indicated for the treatment of adult patients with the following French-American-British (FAB) myelodysplastic syndrome (MDS) subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL). Azacitidine is also indicated for the treatment of pediatric patients aged 1 month and older with newly diagnosed Juvenile Myelomonocytic Leukemia (JMML).15,16

Azacitidine (for oral use) is indicated for continued treatment of adult patients with acute myeloid leukemia (AML) who achieved first complete remission or complete remission with incomplete blood count recovery following intensive induction chemotherapy and are not able to complete intensive curative therapy.13

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAcute myeloid leukemia••••••••••••••••••••••••••
Treatment ofAcute myeloid leukemia (aml)•••••••••••••••••••••••••• ••••••••••••••••••
Treatment ofAcute myeloid leukemia (aml)•••••••••••••••••••••••
Treatment ofChronic myelomonocytic leukemia•••••••••••••••••••••
Treatment ofRefractory anemia•••••••••••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis, and hypomethylation may restore normal function to genes critical for differentiation and proliferation.16 Genome-wide DNA methylation levels in bone marrow granulocytes were reduced in patients with juvenile myelomonocytic leukemia after the first treatment cycle of azacitidine (75 mg/m2 or 2.5 mg/kg), confirming the DNA-hypomethylating activity of azacitidine.16

The use of azacitidine causes anemia, neutropenia and thrombocytopenia in adult patients with myelodysplastic syndrome and pediatric patients with juvenile myelomonocytic leukemia. Azacitidine may cause renal toxicity, tumor lysis syndrome and embryo-fetal toxicity. It may also lead to the development of hepatotoxicity in patients with severe pre-existing hepatic impairment.16

Mechanism of action

Azacitidine (5-azacytidine) is a chemical analogue of the cytosine nucleoside present in DNA and RNA.1,2 It induces antineoplastic activity by inhibiting DNA methyltransferase at low doses and inducing cytotoxicity by incorporating itself into RNA and DNA at high doses.3,4,7

Covalent binding to DNA methyltransferase results in DNA hypomethylation and prevents DNA synthesis.7 On the other hand, the incorporation of azacitidine into RNA and DNA leads to cytotoxicity as follows: Following cellular uptake, azacitidine is phosphorylated by uridine-cytidine kinase to form 5-azacytidine monophosphate. Afterwards, pyrimidine monophosphate and diphosphate kinases phosphorylate 5-azacytidine monophosphate to form 5-azacytidine diphosphate and triphosphate, respectively. Azacitidine triphosphate is able to incorporate into RNA, disrupting RNA metabolism and protein synthesis. The reduction of azacytidine diphosphate leads to the formation of 5-aza-deoxycytidine diphosphate, which is then phosphorylated to form 5-azadeoxycitidine triphosphate, a compound able to incorporate into DNA and inhibit DNA synthesis.2

As a ribonucleoside, azacitidine incorporates into RNA to a larger extent than into DNA. Incorporating into RNA leads to the disassembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and the inhibition of protein production, resulting in cell death. During the S-phase of the cell cycle, azacitidine exhibits the highest toxicity; however, the predominant mechanism of cytotoxicity has not been elucidated.2

The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine. It is believed that azacitidine exerts its antineoplastic effects through direct cytotoxicity on abnormal hematopoietic cells in the bone marrow.16

TargetActionsOrganism
ADNA (cytosine-5)-methyltransferase 1
inhibitor
Humans
ARNA
other
Humans
ADNA
other
Humans
Absorption

Azacitidine is rapidly absorbed after subcutaneous administration.9,16 In adult patients with myelodysplastic syndrome given a single subcutaneous dose of 75 mg/m2 of azacitidine, the Cmax and Tmax were 750 ng/ml and 0.5 hours, respectively. Based on the area under the curve, the bioavailability of subcutaneous azacitidine relative to intravenous azacitidine is approximately 89%. In 21 patients with cancer given subcutaneous azacitidine, the AUC and Cmax were approximately dose-proportional between 25 and 100 mg/m2. Multiple subcutaneous or intravenous doses of azacitidine are not expected to result in drug accumulation.16

Volume of distribution

In patients given an intravenous dose of azacitidine, the volume of distribution is 76 L.16

Protein binding

Not available.

Metabolism

An in vitro study of azacitidine incubation in human liver fractions indicated that cytochrome P450 (CYP) enzymes do not participate in the metabolism of azacitidine. Azacitidine is metabolized through spontaneous hydrolysis and deamination mediated by cytidine deaminase.16

Route of elimination

Azacitidine and its metabolites are mainly excreted through urine.9,16 In five cancer patients given radioactive azacitidine intravenously, the cumulative urinary excretion was 85% of the radioactive dose. Fecal excretion accounted for less than 1% of administered radioactivity over three days. Following the subcutaneous administration of 14C-azacitidine, the mean excretion of radioactivity in urine was 50%.16

Half-life

The mean half-life of azacitidine after subcutaneous administration is 41 minutes. The mean elimination half-life of azacitidine and its metabolites was about 4 hours for intravenous and subcutaneous administrations.16

Clearance

Azacitidine has an apparent subcutaneous clearance of 167 L/hour in adults. In pediatric patients, the geometric mean clearance was 21.8 L/hour.16

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

One case of overdose with azacitidine was reported during clinical trials. After receiving a single dose of 290 mg/m2 of azacitidine intravenously (almost 4 times the recommended starting dose), a patient experienced diarrhea, nausea, and vomiting. These adverse events resolved without sequelae, and the correct dose was resumed the following day. In case of overdose, patients should be monitored with appropriate blood counts and receive supportive treatment as necessary. There is no known specific antidote for azacitidine overdosage.16 In mice, the oral LD50 of azacitidine is 572 mg/kg, while the intravenous LD50 is approximately 117 mg/kg.17

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAzacitidine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Azacitidine is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Azacitidine.
AceclofenacAceclofenac may decrease the excretion rate of Azacitidine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Azacitidine which could result in a higher serum level.
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Images
International/Other Brands
Ladakamycin / Mylosar
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousActavis Pharma, Inc.2016-09-222019-04-30US flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousBluePoint Laboratories2017-07-01Not applicableUS flag
Azacitidine Betapharm25 mg/mLSubcutaneousBetapharm Arzneimittel Gmb H2020-12-23Not applicableEU flag
Azacitidine Celgene25 mg/mlSubcutaneousCelgene Europe Bv2020-12-162021-08-04EU flag
Azacitidine for InjectionPowder, for suspension100 mg / vialSubcutaneousSandoz Canada Incorporated2023-04-17Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousAmneal Pharmaceuticals LLC2022-02-09Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousDr. Reddy's Laboratories Inc.2013-09-19Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/50mLSubcutaneousBluePoint Laboratories2021-06-11Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousArmas Pharmaceuticals Inc.2018-09-10Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousCELLTRION USA, INC.2020-01-06Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Azacitidine AccordAzacitidine (100 mg) + Azacitidine (125 mg)SubcutaneousAccord Healthcare S.L.U.2022-06-06Not applicableEU flag
Azacitidine AccordAzacitidine (100 mg) + Azacitidine (125 mg)SubcutaneousAccord Healthcare S.L.U.2020-12-16Not applicableEU flag
Azacitidine AccordAzacitidine (100 mg) + Azacitidine (125 mg)SubcutaneousAccord Healthcare S.L.U.2022-06-06Not applicableEU flag
Azacitidine AccordAzacitidine (100 mg) + Azacitidine (125 mg)SubcutaneousAccord Healthcare S.L.U.2020-12-16Not applicableEU flag

Categories

ATC Codes
L01BC07 — Azacitidine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as glycosylamines. These are compounds consisting of an amine with a beta-N-glycosidic bond to a carbohydrate, thus forming a cyclic hemiaminal ether bond (alpha-amino ether).
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Glycosylamines
Alternative Parents
Pentoses / Triazinones / Aminotriazines / 1,3,5-triazines / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Oxacyclic compounds / Azacyclic compounds / Primary amines
show 4 more
Substituents
1,3,5-triazine / Alcohol / Amine / Amino-1,3,5-triazine / Aminotriazine / Aromatic heteromonocyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Monosaccharide
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
nucleoside analogue, N-glycosyl-1,3,5-triazine (CHEBI:2038)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
M801H13NRU
CAS number
320-67-2
InChI Key
NMUSYJAQQFHJEW-KVTDHHQDSA-N
InChI
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
IUPAC Name
4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydro-1,3,5-triazin-2-one
SMILES
NC1=NC(=O)N(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O

References

Synthesis Reference

Lorenzo DE FERRA, Maurizio ZENONI, Stefano TURCHETTA, Mauro ANIBALDI, Ettore AMMIRATI, Paolo BRANDI, Giorgio BERARDI, "PROCESS FOR THE SYNTHESIS OF AZACITIDINE AND DECITABINE." U.S. Patent US20110245485, issued October 06, 2011.

US20110245485
General References
  1. Cihak A: Biological effects of 5-azacytidine in eukaryotes. Oncology. 1974;30(5):405-22. [Article]
  2. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R: FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist. 2005 Mar;10(3):176-82. [Article]
  3. Leone G, Voso MT, Teofili L, Lubbert M: Inhibitors of DNA methylation in the treatment of hematological malignancies and MDS. Clin Immunol. 2003 Oct;109(1):89-102. [Article]
  4. Ghoshal K, Bai S: DNA methyltransferases as targets for cancer therapy. Drugs Today (Barc). 2007 Jun;43(6):395-422. [Article]
  5. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF: Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002 May 15;20(10):2429-40. [Article]
  6. Silverman LR: Targeting hypomethylation of DNA to achieve cellular differentiation in myelodysplastic syndromes (MDS). Oncologist. 2001;6 Suppl 5:8-14. [Article]
  7. Issa JP, Kantarjian H: Azacitidine. Nat Rev Drug Discov. 2005 May;Suppl:S6-7. [Article]
  8. O'Dwyer K, Maslak P: Azacitidine and the beginnings of therapeutic epigenetic modulation. Expert Opin Pharmacother. 2008 Aug;9(11):1981-6. doi: 10.1517/14656566.9.11.1981 . [Article]
  9. Siddiqui MA, Scott LJ: Azacitidine: in myelodysplastic syndromes. Drugs. 2005;65(13):1781-9; discussion 1790-1. [Article]
  10. Abdulhaq H, Rossetti JM: The role of azacitidine in the treatment of myelodysplastic syndromes. Expert Opin Investig Drugs. 2007 Dec;16(12):1967-75. [Article]
  11. Keating GM: Azacitidine: a review of its use in higher-risk myelodysplastic syndromes/acute myeloid leukaemia. Drugs. 2009;69(17):2501-18. doi: 10.2165/11202840-000000000-00000. [Article]
  12. Sullivan M, Hahn K, Kolesar JM: Azacitidine: a novel agent for myelodysplastic syndromes. Am J Health Syst Pharm. 2005 Aug 1;62(15):1567-73. [Article]
  13. FDA Approved Drug Products: ONUREG (azacitidine) tablets [Link]
  14. Health Canada Product Monograph: VIDAZA (azacitidine) injection [Link]
  15. FDA Approved Drug Products: VIDAZA (azacitidine) injection, subcutaneous or intravenous use [Link]
  16. FDA Approved Drug Products: VIDAZA (azacitidine) injection, subcutaneous or intravenous use (September 2022) [Link]
  17. Celgene: Azacitidine SDS [Link]
Human Metabolome Database
HMDB0015063
KEGG Drug
D03021
KEGG Compound
C11262
PubChem Compound
9444
PubChem Substance
46509032
ChemSpider
9072
BindingDB
50424715
RxNav
1251
ChEBI
2038
ChEMBL
CHEMBL1489
ZINC
ZINC000003861768
Therapeutic Targets Database
DAP000640
PharmGKB
PA451996
PDBe Ligand
5AE
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Azacitidine
PDB Entries
4qd3

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentAcute Myeloid Leukemia1
4CompletedTreatmentMyelodysplastic Syndrome1
4Not Yet RecruitingTreatmentMyelodysplastic Syndrome1
4RecruitingTreatmentAcute Myeloid Leukaemia; Myelodysplastic Syndromes;Chronic Myelomonocytic Leukemia1
4TerminatedTreatmentMyelodysplastic Syndrome1

Pharmacoeconomics

Manufacturers
  • Celgene corp
Packagers
  • Baxter International Inc.
  • Ben Venue Laboratories Inc.
  • Celgene
  • Pharmion LLC
Dosage Forms
FormRouteStrength
Injection, powder, for suspensionSubcutaneous
Injection, powder, lyophilized, for suspensionSubcutaneous100 mg/ml
Injection, powder, for suspension25 mg/ml
PowderSubcutaneous25 MG/ML
Powder
Powder25 MG/ML
PowderParenteral25 MG/ML
Injection, powder, lyophilized, for solutionIntravenous; Subcutaneous100 mg/4mL
Injection, powder, lyophilized, for solutionIntravenous; Subcutaneous100 mg/30mL
Injection, powder, lyophilized, for solutionIntravenous; Subcutaneous100 mg/1
Injection, powder, lyophilized, for solutionIntravenous; Subcutaneous100 mg/50mL
Injection, powder, lyophilized, for solutionSubcutaneous100 mg/50mL
Powder, for suspensionSubcutaneous150 mg / vial
PowderIntravenous; Subcutaneous100 mg
Injection, powder, for solution100 mg/1vial
Injection, powder, lyophilized, for suspensionSubcutaneous100 mg/1vial
Injection, powder, for suspensionIntravenous; Subcutaneous
Injection, powder, lyophilized, for suspensionSubcutaneous100 mg
InjectionSubcutaneous
SuspensionSubcutaneous100.00 mg
PowderIntravenous100 mg
TabletOral200 mg
TabletOral300 mg
Tablet, film coatedOral200 MG
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral300 MG
Tablet, film coatedOral300 mg/1
Injection, powder, lyophilized, for solutionIntravenous; Subcutaneous100 mg
SolutionSubcutaneous100.000 mg
SolutionSubcutaneous100.00 mg
Injection, powder, lyophilized, for suspensionSubcutaneous100 mg/4mL
PowderParenteral; Subcutaneous25 MG/ML
Powder, for suspensionSubcutaneous100 mg / vial
SuspensionSubcutaneous100.000 mg
Injection, powder, lyophilized, for suspensionSubcutaneous
Injection, powder, for suspensionSubcutaneous100 mg
Injection, powder, for suspensionIntravenous; Subcutaneous100 mg
InjectionSubcutaneous100 mg
Powder100 mg/1vial
Prices
Unit descriptionCostUnit
Vidaza 100 mg vial588.23USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8846628No2014-09-302030-06-03US flag
US11571436No2009-05-142029-05-14US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)229 °CPhysProp
water solubility8.9E+004 mg/LNot Available
logP-3.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility12.1 mg/mLALOGPS
logP-2.4ALOGPS
logP-3.1Chemaxon
logS-1.3ALOGPS
pKa (Strongest Acidic)12.55Chemaxon
pKa (Strongest Basic)1.96Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area140.97 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity52.19 m3·mol-1Chemaxon
Polarizability21.5 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9509
Blood Brain Barrier+0.8753
Caco-2 permeable-0.8715
P-glycoprotein substrateNon-substrate0.7879
P-glycoprotein inhibitor INon-inhibitor0.9591
P-glycoprotein inhibitor IINon-inhibitor0.9671
Renal organic cation transporterNon-inhibitor0.9355
CYP450 2C9 substrateNon-substrate0.8103
CYP450 2D6 substrateNon-substrate0.8572
CYP450 3A4 substrateNon-substrate0.6067
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9436
CYP450 2D6 inhibitorNon-inhibitor0.9438
CYP450 2C19 inhibitorNon-inhibitor0.9329
CYP450 3A4 inhibitorNon-inhibitor0.9617
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9839
Ames testAMES toxic0.8058
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable0.8432
Rat acute toxicity1.7991 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9794
hERG inhibition (predictor II)Non-inhibitor0.8996
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-08nc-9420000000-deb4c3c2e01ce611d805
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0900000000-0926f2f5f469326aa30b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0hfx-9450000000-50b1083709142293ee8a
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-2900000000-0ba55a50b07145eb1ddd
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-9100000000-d40e54e58e9eb978a5a6
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kf-9000000000-76d796b375338cbb893a
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-022a-9400000000-466015d5596da2aaa07d
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-161.3006852
predicted
DarkChem Lite v0.1.0
[M-H]-161.0279852
predicted
DarkChem Lite v0.1.0
[M-H]-160.6494852
predicted
DarkChem Lite v0.1.0
[M-H]-149.57274
predicted
DeepCCS 1.0 (2019)
[M+H]+161.2781852
predicted
DarkChem Lite v0.1.0
[M+H]+162.0811852
predicted
DarkChem Lite v0.1.0
[M+H]+161.4730852
predicted
DarkChem Lite v0.1.0
[M+H]+151.9683
predicted
DeepCCS 1.0 (2019)
[M+Na]+160.7080852
predicted
DarkChem Lite v0.1.0
[M+Na]+161.2826852
predicted
DarkChem Lite v0.1.0
[M+Na]+158.94322
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is ...
Gene Name
DNMT1
Uniprot ID
P26358
Uniprot Name
DNA (cytosine-5)-methyltransferase 1
Molecular Weight
183163.635 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R: FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist. 2005 Mar;10(3):176-82. [Article]
  3. Cataldo VD, Cortes J, Quintas-Cardama A: Azacitidine for the treatment of myelodysplastic syndrome. Expert Rev Anticancer Ther. 2009 Jul;9(7):875-84. doi: 10.1586/era.09.61. [Article]
  4. Leone G, Voso MT, Teofili L, Lubbert M: Inhibitors of DNA methylation in the treatment of hematological malignancies and MDS. Clin Immunol. 2003 Oct;109(1):89-102. [Article]
  5. Ghoshal K, Bai S: DNA methyltransferases as targets for cancer therapy. Drugs Today (Barc). 2007 Jun;43(6):395-422. [Article]
  6. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF: Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002 May 15;20(10):2429-40. [Article]
  7. Fenaux P: Inhibitors of DNA methylation: beyond myelodysplastic syndromes. Nat Clin Pract Oncol. 2005 Dec;2 Suppl 1:S36-44. [Article]
  8. Silverman LR: Targeting hypomethylation of DNA to achieve cellular differentiation in myelodysplastic syndromes (MDS). Oncologist. 2001;6 Suppl 5:8-14. [Article]
  9. O'Dwyer K, Maslak P: Azacitidine and the beginnings of therapeutic epigenetic modulation. Expert Opin Pharmacother. 2008 Aug;9(11):1981-6. doi: 10.1517/14656566.9.11.1981 . [Article]
  10. Hollenbach PW, Nguyen AN, Brady H, Williams M, Ning Y, Richard N, Krushel L, Aukerman SL, Heise C, MacBeth KJ: A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One. 2010 Feb 2;5(2):e9001. doi: 10.1371/journal.pone.0009001. [Article]
  11. Glover AB, Leyland-Jones B: Biochemistry of azacitidine: a review. Cancer Treat Rep. 1987 Oct;71(10):959-64. [Article]
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Other
References
  1. Muller A, Florek M: 5-Azacytidine/Azacitidine. Recent Results Cancer Res. 2010;184:159-70. doi: 10.1007/978-3-642-01222-8_11. [Article]
  2. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R: FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist. 2005 Mar;10(3):176-82. [Article]
  3. Hollenbach PW, Nguyen AN, Brady H, Williams M, Ning Y, Richard N, Krushel L, Aukerman SL, Heise C, MacBeth KJ: A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One. 2010 Feb 2;5(2):e9001. doi: 10.1371/journal.pone.0009001. [Article]
  4. Glover AB, Leyland-Jones B: Biochemistry of azacitidine: a review. Cancer Treat Rep. 1987 Oct;71(10):959-64. [Article]
  5. Cihak A, Vesely J, Skoda J: Azapyrimidine nucleosides: metabolism and inhibitory mechanisms. Adv Enzyme Regul. 1985;24:335-54. [Article]
  6. Dapp MJ, Clouser CL, Patterson S, Mansky LM: 5-Azacytidine can induce lethal mutagenesis in human immunodeficiency virus type 1. J Virol. 2009 Nov;83(22):11950-8. doi: 10.1128/JVI.01406-09. Epub 2009 Sep 2. [Article]
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Other
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Allen A: Epigenetic alterations and cancer: new targets for therapy. IDrugs. 2007 Oct;10(10):709-12. [Article]
  4. Kaminskas E, Farrell AT, Wang YC, Sridhara R, Pazdur R: FDA drug approval summary: azacitidine (5-azacytidine, Vidaza) for injectable suspension. Oncologist. 2005 Mar;10(3):176-82. [Article]
  5. O'Dwyer K, Maslak P: Azacitidine and the beginnings of therapeutic epigenetic modulation. Expert Opin Pharmacother. 2008 Aug;9(11):1981-6. doi: 10.1517/14656566.9.11.1981 . [Article]
  6. Muller A, Florek M: 5-Azacytidine/Azacitidine. Recent Results Cancer Res. 2010;184:159-70. doi: 10.1007/978-3-642-01222-8_11. [Article]
  7. Hollenbach PW, Nguyen AN, Brady H, Williams M, Ning Y, Richard N, Krushel L, Aukerman SL, Heise C, MacBeth KJ: A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines. PLoS One. 2010 Feb 2;5(2):e9001. doi: 10.1371/journal.pone.0009001. [Article]
  8. Glover AB, Leyland-Jones B: Biochemistry of azacitidine: a review. Cancer Treat Rep. 1987 Oct;71(10):959-64. [Article]
  9. Cihak A, Vesely J, Skoda J: Azapyrimidine nucleosides: metabolism and inhibitory mechanisms. Adv Enzyme Regul. 1985;24:335-54. [Article]
  10. Dapp MJ, Clouser CL, Patterson S, Mansky LM: 5-Azacytidine can induce lethal mutagenesis in human immunodeficiency virus type 1. J Virol. 2009 Nov;83(22):11950-8. doi: 10.1128/JVI.01406-09. Epub 2009 Sep 2. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Zinc ion binding
Specific Function
This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
Gene Name
CDA
Uniprot ID
P32320
Uniprot Name
Cytidine deaminase
Molecular Weight
16184.545 Da
References
  1. Garcia-Manero G, Stoltz ML, Ward MR, Kantarjian H, Sharma S: A pilot pharmacokinetic study of oral azacitidine. Leukemia. 2008 Sep;22(9):1680-4. doi: 10.1038/leu.2008.145. Epub 2008 Jun 12. [Article]

Drug created at June 13, 2005 13:24 / Updated at February 24, 2024 21:59