Details of the Drug

General Information of Drug (ID: DMQL8XJ)

• Drug Name: Decitabine
• Synonyms: AzadC; Dacogen; Dezocitidine; NCGC_5ADOC; Dacogen (TN); E-7373; Decitabine (USAN/INN); Dacogen, 5-aza-2'-deoxycytidine,NSC 127716, Dacogen, DAC, Decitabine; 2'-Deoxy-5-azacytidine; 4-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one; 4-Amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-s-triazin-2(1H)-one; 4-Amino-1-(2-deoxy-beta-D-ribofuranosyl)-1,3,5-triazin-2(1H)-one; 4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one; 5-AZAdC; 5-Aza-2′-Deoxycytidine; 5-Aza-2'-deoxycytidine; 5-Azadeoxycytidine; 5-Deoxy-2′-azacytidine; 5-aza-2-deoxycytidine; 5-aza-CdR; 5-aza-dC; 5A2dc

Indication

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[1]
Adult acute monocytic leukemia	N.A.	Approved	[1]
Myelodysplastic syndrome	2A37	Approved	[2]
Refractory chronic myeloid leukaemia	2A20	Approved	[1]

• Therapeutic Class: Anticancer Agents
• Affected Organisms: Humans and other mammals
• ATC Code:
  L01BC08: Decitabine
  L01BC: Pyrimidine analogues
  L01B: ANTIMETABOLITES
  L01: ANTINEOPLASTIC AGENTS
  L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 228.21
  Logarithm of the Partition Coefficient (xlogp); -1.2
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 1332 mcgh/L [3]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 73.8 mcg/L [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 130 mL/min/kg [4]
  Elimination: Less than 1% of administered decitabine is excreted in the urine [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 0.62 hours [3]
  Metabolism: The drug is metabolized via the sequential action of deoxycytidine kinase, nucleotide monophosphate kinase, and nucleotide diphosphate kinase [6]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 4.8733 micromolar/kg/day [7]
  Unbound Fraction: The unbound fraction of drug in plasma is 1% [4]
  Vd: The volume of distribution (Vd) of drug is 4.59 +/- 1.42 L/kg [5]
• Chemical Identifiers:
  Formula: C8H12N4O4
  IUPAC Name: 4-amino-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3,5-triazin-2-one
  Canonical SMILES: C1[C@@H]([C@H](O[C@H]1N2C=NC(=NC2=O)N)CO)O
  InChI: InChI=1S/C8H12N4O4/c9-7-10-3-12(8(15)11-7)6-1-4(14)5(2-13)16-6/h3-6,13-14H,1-2H2,(H2,9,11,15)/t4-,5+,6+/m0/s1
  InChIKey: XAUDJQYHKZQPEU-KVQBGUIXSA-N
• Cross-matching ID:
  PubChem CID: 451668
  ChEBI ID: CHEMBL1201129
  CAS Number: 2353-33-5
  UNII: 776B62CQ27
  DrugBank ID: DB01262
  TTD ID: D0X5XU
  INTEDE ID: DR1763
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[8]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytidine aminohydrolase (CDA)	DEKEDRC	CDD_HUMAN	Substrate	[9]
Cytidine deaminase (cdd)	DEYILK4	E0TLJ6_MYCHH	Substrate	[10]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1-acyl-sn-glycerol-3-phosphate acyltransferase beta (AGPAT2)	OT5I4Y9K	PLCB_HUMAN	Gene/Protein Processing	[11]
1-acylglycerol-3-phosphate O-acyltransferase ABHD5 (ABHD5)	OTY829Z3	ABHD5_HUMAN	Gene/Protein Processing	[12]
1-aminocyclopropane-1-carboxylate synthase-like protein 1 (ACCS)	OTHIHI9D	1A1L1_HUMAN	Gene/Protein Processing	[12]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCG2)	OTGVC9MY	PLCG2_HUMAN	Gene/Protein Processing	[12]
14 kDa phosphohistidine phosphatase (PHPT1)	OTFYWNFX	PHP14_HUMAN	Gene/Protein Processing	[12]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Gene/Protein Processing	[13]
17-beta-hydroxysteroid dehydrogenase 14 (HSD17B14)	OT0ETO72	DHB14_HUMAN	Gene/Protein Processing	[12]
182 kDa tankyrase-1-binding protein (TNKS1BP1)	OTBIZECQ	TB182_HUMAN	Gene/Protein Processing	[14]
2'-5'-oligoadenylate synthase 2 (OAS2)	OT64CCTM	OAS2_HUMAN	Gene/Protein Processing	[15]
26S proteasome non-ATPase regulatory subunit 12 (PSMD12)	OTWICA51	PSD12_HUMAN	Gene/Protein Processing	[12]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Decitabine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Decitabine and Roflumilast.	Asthma [CA23]	[16]
Teriflunomide	DMQ2FKJ	Major	Additive myelosuppressive effects by the combination of Decitabine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[17]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of Decitabine and Denosumab.	Low bone mass disorder [FB83]	[18]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Decitabine and Tecfidera.	Multiple sclerosis [8A40]	[19]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Decitabine and Siponimod.	Multiple sclerosis [8A40]	[20]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Decitabine and Fingolimod.	Multiple sclerosis [8A40]	[21]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Decitabine and Ocrelizumab.	Multiple sclerosis [8A40]	[22]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Decitabine and Ozanimod.	Multiple sclerosis [8A40]	[16]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Decitabine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[23]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Decitabine and Canakinumab.	Rheumatoid arthritis [FA20]	[24]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Decitabine and Rilonacept.	Rheumatoid arthritis [FA20]	[24]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Decitabine and Golimumab.	Rheumatoid arthritis [FA20]	[25]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Decitabine when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[26]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Decitabine and Valganciclovir.	Virus infection [1A24-1D9Z]	[20]

References

• [1] Decitabine FDA Label
• [2] 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: 6805).
• [3] FDA Approved Drug Products: decitabine for injection
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Saba HI, Wijermans PW: Decitabine in myelodysplastic syndromes. Semin Hematol. 2005 Jul;42(3 Suppl 2):S23-31.
• [6] Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25.
• [7] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [8] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [9] Tracking decitabine incorporation into malignant myeloid cell DNA in vitro and in vivo by LC-MS/MS with enzymatic digestion. Sci Rep. 2019 Mar 14;9(1):4558.
• [10] Mycoplasma hyorhinis-encoded cytidine deaminase efficiently inactivates cytosine-based anticancer drugs. FEBS Open Bio. 2015 Aug 3;5:634-9.
• [11] Gene induction and apoptosis in human hepatocellular carci-noma cells SMMC-7721 exposed to 5-aza-2'-deoxycytidine. Chin Med J (Engl). 2007 Sep 20;120(18):1626-31.
• [12] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [13] Cell cycle regulation of human endometrial stromal cells during decidualization. Reprod Sci. 2012 Aug;19(8):883-94. doi: 10.1177/1933719112438447. Epub 2012 Apr 24.
• [14] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [15] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [16] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [17] Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
• [18] Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
• [19] Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
• [20] Cerner Multum, Inc. "Australian Product Information.".
• [21] Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
• [22] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [23] Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
• [24] Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
• [25] Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
• [26] CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]