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

A pyrimidine nucleoside analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
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
  • NSC-102816
  • U-18,496
  • U-18496

Pharmacology

Indication

For treatment of patients with the following French-American-British myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation (now classified as acute myelogenous leukemia with multilineage dysplasia), and chronic myelomonocytic leukemia.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. 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. Upon uptake into cells, azacitidine is phosphorylated to 5-azacytidine monophosphate by uridine-cytidine kinase, then to diphosphate by pyrimidine monophosphate kinases and triphosphate by diphosphate kinases. 5-Azacitidine triphosphate is incorporated into RNA, leading to the disruption of nuclear and cytoplasmic RNA metabolism and inhibition of protein synthesis. 5-Azacytidine diphosphate is reduced to 5-aza-deoxycytidine diphosphate by ribonucleotide reductase. The resultant metabolite is phosphorylated to 5-azadeoxycitidine triphosphate by nucleoside diphosphate kinases. 5-azadeoxycitidine triphosphate is then incoporated into DNA, leading to inhibition of DNA synthesis. Azacitidine is most toxic during the S-phase of the cell cycle.

Mechanism of action

Azacitidine (5-azacytidine) is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine may induce antineoplastic activity by inhibition of DNA methyltransferase at low doses and cytotoxicity through incorporation into RNA and DNA at high doses. Covalent binding to DNA methyltransferase results in hypomethylation of DNA and prevents DNA synthesis. As azacitidine is a ribonucleoside, it incoporates into RNA to a larger extent than into DNA. The incorporation into RNA leads to the dissembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of protein, resulting in cell death.

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

Azacitidine is rapidly absorbed after subcutaneous administration. The bioavailability of subcutaneous azacitidine relative to IV azacitidine is approximately 89%, based on area under the curve.

Volume of distribution
  • 76 ± 26 L
Protein binding

Not Available

Metabolism

An in vitro study of azacitidine incubation in human liver fractions indicated that azacitidine may be metabolized by the liver. The potential of azacitidine to inhibit cytochrome P450 (CYP) enzymes is not known.

Route of elimination

Following IV administration of radioactive azacitidine to 5 cancer patients, the cumulative urinary excretion was 85% of the radioactive dose. Fecal excretion accounted for <1% of administered radioactivity over three days. Mean excretion of radioactivity in urine following SC administration of 14C-azacitidine was 50%.

Half-life

Mean elimination half-life is approximately 4 hours.

Clearance
  • 167 +/- 49 L/h
Adverse Effects
Adverseeffects
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Toxicity

One case of overdose with azacitidine was reported during clinical trials. A patient experienced diarrhea, nausea, and vomiting after receiving a single IV dose of approximately 290 mg/m2, almost 4 times the recommended starting dose.

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.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Azacitidine.
AcetaminophenAcetaminophen may decrease the excretion rate of Azacitidine which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Azacitidine which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Azacitidine.
AclidiniumAzacitidine may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Interactions
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Food Interactions
No interactions found.

Products

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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 Accord25 mg/mlSubcutaneousAccord Healthcare S.L.U.2020-12-16Not applicableEU 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 / vialSubcutaneousFresenius KabiNot applicableNot applicableCanada flag
Azacitidine for InjectionPowder, for suspension100 mg / vialSubcutaneousJamp Pharma CorporationNot applicableNot applicableCanada flag
Azacitidine for InjectionPowder, for suspension100 mg / vialSubcutaneousHikma Canada LimitedNot applicableNot applicableCanada flag
Azacitidine for InjectionPowder, for suspension100 mg / vialSubcutaneousDr Reddy's Laboratories2017-10-25Not applicableCanada flag
Azacitidine Mylan25 mg/mlSubcutaneousMylan Ireland Limited2020-12-23Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousDr. Reddy's Laboratories Inc.2013-09-19Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousSandoz Inc2014-03-27Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/50mLSubcutaneousPanacea Biotec Limited2019-05-06Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/30mLIntravenous; SubcutaneousMeitheal Pharmaceuticals Inc.2020-11-02Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousArmas Pharmaceuticals Inc.2018-09-10Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousCipla USA Inc.2018-05-04Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousMylan Institutional LLC2016-05-23Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousWockhardt USA LLC.2016-09-29Not applicableUS flag64679 09620180907 15195 yznuaa
AzacitidineInjection, powder, lyophilized, for solution100 mg/50mLSubcutaneousBluePoint Laboratories2021-06-11Not applicableUS flag
AzacitidineInjection, powder, lyophilized, for solution100 mg/1Intravenous; SubcutaneousSandoz Inc2013-09-16Not applicableUS 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. 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]
  14. FDA Approved Drug Products: VIDAZA (azacitidine) injection [Link]
  15. FDA Approved Drug Products: ONUREG (azacitidine) tablets [Link]
  16. Health Canada Product Monograph: VIDAZA (azacitidine) injection [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
FDA label
Download (194 KB)
MSDS
Download (68.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentMyelodysplastic Syndromes (MDS)1
4RecruitingTreatmentAcute Myeloid Leukaemia; Myelodysplastic Syndromes;Chronic Myelomonocytic Leukemia1
4TerminatedTreatmentMyelodysplastic Syndromes (MDS)1
3Active Not RecruitingTreatmentAcute Myeloid Leukemia (AML)4
3Active Not RecruitingTreatmentAcute Myeloid Leukemia (AML) / Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) Mutation1
3Active Not RecruitingTreatmentAcute Myeloid Leukemia (AML) / AML Arising From Myelodysplastic Syndrome (MDS) / Newly Diagnosed Acute Myeloid Leukemia (AML) / Untreated AML1
3Active Not RecruitingTreatmentAcute Myeloid Leukemia (AML) / Chronic Myelomonocytic Leukemia (CMML) / Coronavirus Disease 2019 (COVID‑19) / Myelodysplastic Syndromes (MDS)1
3Active Not RecruitingTreatmentAcute Myeloid Leukemia (AML) / Chronic Myelomonocytic Leukemia (CMML) / Myelodysplastic Syndromes (MDS)1
3Active Not RecruitingTreatmentAcute Myeloid Leukemia (AML) / Malignancies1
3Active Not RecruitingTreatmentIsocitrate Dehydrogenase / Myeloid Leukemias1

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 suspension
PowderSubcutaneous25 MG/ML
Powder
Powder25 MG/ML
PowderParenteral25 MG/ML
Injection, powder, lyophilized, for solutionIntravenous; Subcutaneous100 mg/30mL
Injection, powder, lyophilized, for solutionIntravenous; Subcutaneous100 mg/1
Injection, powder, lyophilized, for solutionSubcutaneous100 mg/50mL
PowderIntravenous; Subcutaneous100 mg
Injection, powder, for solution100 mg/1vial
InjectionSubcutaneous
Injection, powder, lyophilized, for suspensionSubcutaneous100 mg/1vial
Injection, powder, for suspensionIntravenous; Subcutaneous
Injection, powder, lyophilized, for suspensionSubcutaneous100 mg
PowderIntravenous100 mg
TabletOral200 mg
TabletOral300 mg
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral300 mg/1
Injection, powder, lyophilized, for solutionIntravenous; Subcutaneous100 mg
Injection, powder, lyophilized, for suspensionSubcutaneous100 mg/4mL
PowderParenteral; Subcutaneous25 MG/ML
Powder, for suspensionSubcutaneous100 mg / vial
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

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)-0.38ChemAxon
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Targets

Drugtargets2
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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 on June 13, 2005 13:24 / Updated on October 22, 2021 23:18