Details of the Drug

General Information of Drug (ID: DMZD5QR)

Drug Name

Cytarabine

Synonyms

Alexan; AraC; Arabinocytidine; Arabinofuranosylcytosine; Arabinosylcytosine; Arabitin; Aracytidine; Aracytin; Aracytine; Arafcyt; Citarabina; Cytarabin; Cytarabina; Cytarabinoside; Cytarabinum; Cytarbel; Cytonal; Cytosar; Cytosinearabinoside; DepoCyte; Depocyt; Erpalfa; Iretin; Spongocytidine; Tarabine; Udicil; Arabinosyl Cytosine; Cytarabine liposome injection; Cytosine arabinofuranoside; Cytosine arabinose; Cytosine arabinoside; AR3; BTB15125; CHX 3311; U 19920A; Ara-C; Ara-Cytidine; Beta-Ara C; Beta-Arabinosylcytosine; Beta-cytosine arabinoside; Citarabina [INN-Spanish]; Cytarabinum [INN-Latin]; Cytosar-U; Cytosine arabinoside (VAN); Depocyt (TN); Depocyt (liposomal); Intrathecal (injected into the spinal fluid) DepoCyt; U-19920; Beta-D-Arabinosylcytosine; Cytosar-U (TN); Cytosine beta-D-arabinofuranoside; Cytosine beta-D-arabinofuranoside hydrochloride; Cytosine beta-D-arabinoside; Cytosine-beta-arabinoside; Intrathecal cytarabine (also known as ara-C); U-19,920; CYTARABINE (SEE ALSO CYTARABINE HYDROCHLORIDE 69-74-9); Cytarabine (JP15/USP/INN); Cytarabine [USAN:INN:BAN:JAN]; Cytosine 1-beta-D-arabinofuranoside; Cytosine, beta-D-arabinoside; Cytosine-beta-D-arabinofuranoside; Cytosine-1-beta-D-arabinofuranoside; Ara-C, Cytosine Arabinoside, Cytosar-U, Cytarabine; (beta-D-Arabinofuranosyl)cytosine; 1-.beta.-D-arabinofuranosyl-cytosine; 1-Arabinofuranosylcytosine; 1-beta-D-Arabinofaranosylcytosine; 1-beta-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-beta-D-Arabinofuranosylcytosine; 1-beta-D-Arabinofuranosylcytosine, Cytosine Arabinoside; 1-beta-D-Arabinosylcytosine; 1beta-Arabinofuranasylcytosine; 1beta-D-Arabinofuranosylcytosine; 1beta-D-Arabinosylcytosine; 2(1H)-Pyrimidinone, 4-amino-1-D-arabinofuranosyl-[CAS]; 4-Amino-1-arabinofuranosyl-2-oxo-1,2-dihydropyrimidin; 4-Amino-1-arabinofuranosyl-2-oxo-1,2-dihydropyrimidin [Czech]; 4-Amino-1-arabinofuranosyl-2-oxo-1,2-dihydropyrimidine; 4-Amino-1-b-D-arabinofuranosyl-2-(1H)-pyrimidinone; 4-Amino-1-beta-D-arabinofuranosyl-2(1H)-pyrimidinon; 4-Amino-1-beta-D-arabinofuranosyl-2(1H)-pyrimidinon [Czech]; 4-Amino-1-beta-D-arabinofuranosyl-2(1H)-pyrimidinone; 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one; 4-amino-1-beta-D-arabinofuranosylpyrimidin-2(1H)-one

Indication

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[1]
Acute myelogenous leukaemia	2A41	Approved	[2]
Adult acute monocytic leukemia	N.A.	Approved	[2]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[2]
Plasma cell myeloma	2A83.1	Approved	[2]
Neoplastic meningitis	N.A.	Investigative	[2]
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⏷ Show the Full List of Indication(s)

Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

243.22

Logarithm of the Partition Coefficient (xlogp)

-2.1

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption: The absorption of drug is less than 20% from the gastrointestinal tract []
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Clearance: The drug present in the plasma can be removed from the body at the rate of 41.67 mL/min/kg [4]
Elimination: 11% of drug is excreted from urine in the unchanged form [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 10 minutes [4]
Metabolism: The drug is metabolized via the hepatic []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 11.10101 micromolar/kg/day [5]
Unbound Fraction: The unbound fraction of drug in plasma is 0.87% [4]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.67 L/kg [4]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Cell-mediated cytotoxicity	Not Available	IL3	OT0CQ35N	[6]
Cell-mediated cytotoxicity	Not Available	HGF	OTGHUA23	[6]
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Chemical Identifiers

Formula: C9H13N3O5
IUPAC Name: 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
Canonical SMILES: C1=CN(C(=O)N=C1N)[C@H]2[C@H]([C@@H]([C@H](O2)CO)O)O
InChI: InChI=1S/C9H13N3O5/c10-5-1-2-12(9(16)11-5)8-7(15)6(14)4(3-13)17-8/h1-2,4,6-8,13-15H,3H2,(H2,10,11,16)/t4-,6-,7+,8-/m1/s1
InChIKey: UHDGCWIWMRVCDJ-CCXZUQQUSA-N

Cross-matching ID

PubChem CID: 6253
ChEBI ID: CHEBI:28680
CAS Number: 147-94-4
DrugBank ID: DB00987
TTD ID: D07XSN
VARIDT ID: DR00416
INTEDE ID: DR0398
ACDINA ID: D00976

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Herpes simplex virus DNA polymerase UL30 (HSV UL30)	TTIU7X1	DPOL_HHV11	Inhibitor	[7]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Equilibrative nucleoside transporter 2 (SLC29A2)	DTW78DQ	S29A2_HUMAN	Substrate	[8]
Concentrative nucleoside transporter 1 (SLC28A1)	DT0EQPW	S28A1_HUMAN	Substrate	[8]
Equilibrative nucleoside transporter 1 (SLC29A1)	DTXD1TQ	S29A1_HUMAN	Substrate	[8]
Organic cation/carnitine transporter 1 (SLC22A4)	DT2EG60	S22A4_HUMAN	Substrate	[9]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[10]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[12]
Cytidine aminohydrolase (CDA)	DEKEDRC	CDD_HUMAN	Substrate	[13]
Ecto-5'-nucleotidase (NT5E)	DE3Z9HM	5NTD_HUMAN	Substrate	[13]
Deoxycytidylate deaminase (DCTD)	DEXL3P2	DCTD_HUMAN	Substrate	[13]
Cytidine deaminase (cdd)	DEYILK4	E0TLJ6_MYCHH	Substrate	[14]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 (PLCB2)	OTPAHDGO	PLCB2_HUMAN	Protein Interaction/Cellular Processes	[15]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1 (PLCH1)	OT6Z1L2E	PLCH1_HUMAN	Gene/Protein Processing	[16]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Drug Response	[17]
3',5'-cyclic-AMP phosphodiesterase 4B (PDE4B)	OTOA8WU2	PDE4B_HUMAN	Gene/Protein Processing	[16]
5'-3' exonuclease PLD3 (PLD3)	OTL07SP2	PLD3_HUMAN	Gene/Protein Processing	[16]
A disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1)	OTTLJH8W	ATS1_HUMAN	Gene/Protein Processing	[16]
A disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9)	OTV3Q0DS	ATS9_HUMAN	Gene/Protein Processing	[16]
Actin filament-associated protein 1-like 2 (AFAP1L2)	OTJBI0VN	AF1L2_HUMAN	Gene/Protein Processing	[16]
Actin, alpha cardiac muscle 1 (ACTC1)	OTJU04B1	ACTC_HUMAN	Gene/Protein Processing	[16]
Actin, alpha skeletal muscle (ACTA1)	OTOVGLPG	ACTS_HUMAN	Gene/Protein Processing	[16]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Cytarabine and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[18]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Cytarabine and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[19]
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Cytarabine and Roflumilast.	Asthma [CA23]	[20]
Ofloxacin	DM0VQN3	Minor	Decreased absorption of Cytarabine due to intestinal mucosa variation caused by Ofloxacin.	Bacterial infection [1A00-1C4Z]	[21]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Cytarabine due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[21]
Gemifloxacin	DMHT34O	Minor	Decreased absorption of Cytarabine due to intestinal mucosa variation caused by Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[21]
Norfloxacin	DMIZ6W2	Minor	Decreased absorption of Cytarabine due to intestinal mucosa variation caused by Norfloxacin.	Bacterial infection [1A00-1C4Z]	[21]
ABT-492	DMJFD2I	Minor	Decreased absorption of Cytarabine due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[21]
Levofloxacin	DMS60RB	Minor	Decreased absorption of Cytarabine due to intestinal mucosa variation caused by Levofloxacin.	Bacterial infection [1A00-1C4Z]	[21]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Cytarabine and Cannabidiol.	Epileptic encephalopathy [8A62]	[20]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Cytarabine and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[22]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Cytarabine and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[23]
Teriflunomide	DMQ2FKJ	Major	Additive immunosuppressive effects by the combination of Cytarabine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[24]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Cytarabine and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[25]
Denosumab	DMNI0KO	Moderate	Additive immunosuppressive effects by the combination of Cytarabine and Denosumab.	Low bone mass disorder [FB83]	[26]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Cytarabine and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[27]
Fludarabine	DMVRLT7	Moderate	Additive myelosuppressive effects by the combination of Cytarabine and Fludarabine.	Malignant haematopoietic neoplasm [2B33]	[28]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Cytarabine and Idelalisib.	Mature B-cell leukaemia [2A82]	[29]
Thalidomide	DM70BU5	Major	Additive thrombogenic effects by the combination of Cytarabine and Thalidomide.	Multiple myeloma [2A83]	[30]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Cytarabine and Tecfidera.	Multiple sclerosis [8A40]	[31]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Cytarabine and Siponimod.	Multiple sclerosis [8A40]	[18]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Cytarabine and Fingolimod.	Multiple sclerosis [8A40]	[32]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Cytarabine and Ocrelizumab.	Multiple sclerosis [8A40]	[33]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Cytarabine and Ozanimod.	Multiple sclerosis [8A40]	[20]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive myelosuppressive effects by the combination of Cytarabine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[34]
Gatifloxacin	DMSL679	Minor	Decreased absorption of Cytarabine due to intestinal mucosa variation caused by Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[21]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Cytarabine and Canakinumab.	Rheumatoid arthritis [FA20]	[35]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Cytarabine and Rilonacept.	Rheumatoid arthritis [FA20]	[35]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Cytarabine and Golimumab.	Rheumatoid arthritis [FA20]	[36]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Cytarabine and Leflunomide.	Rheumatoid arthritis [FA20]	[24]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Cytarabine when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[37]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Cytarabine and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[20]
Azathioprine	DMMZSXQ	Moderate	Additive myelosuppressive effects by the combination of Cytarabine and Azathioprine.	Transplant rejection [NE84]	[18]
Ganciclovir	DM1MBYQ	Moderate	Additive myelosuppressive effects by the combination of Cytarabine and Ganciclovir.	Virus infection [1A24-1D9Z]	[18]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Cytarabine and Valganciclovir.	Virus infection [1A24-1D9Z]	[18]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Hydrochloric acid	E00015	313	Acidulant
Sodium chloride	E00077	5234	Diluent; Tonicity agent
Sodium hydroxide	E00234	14798	Alkalizing agent
Water	E00035	962	Solvent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Cytarabine 100mg/5ml solution	100mg/5ml	Solution	Intravenous; Subcutaneous
Cytarabine 2g/20ml solution	2g/20ml	Solution	Intravenous; Subcutaneous

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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2	Cytarabine FDA Label
3	BDDCS applied to over 900 drugs
4	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5	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
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7	Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. Mol Cancer Ther. 2009 Apr;8(4):864-72.
8	FLT3 is implicated in cytarabine transport by human equilibrative nucleoside transporter 1 in pediatric acute leukemia. Oncotarget. 2016 Aug 2;7(31):49786-49799.
9	OCTN1 Is a High-Affinity Carrier of Nucleoside Analogues. Cancer Res. 2017 Apr 15;77(8):2102-2111.
10	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
11	Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
12	Synthesis and characterization of a novel liver-targeted prodrug of cytosine-1-beta-D-arabinofuranoside monophosphate for the treatment of hepatocellular carcinoma. J Med Chem. 2006 Dec 28;49(26):7711-20.
13	Genetic factors influencing cytarabine therapy. Pharmacogenomics. 2009 Oct;10(10):1657-74.
14	Mycoplasma hyorhinis-encoded cytidine deaminase efficiently inactivates cytosine-based anticancer drugs. FEBS Open Bio. 2015 Aug 3;5:634-9.
15	Protein kinase CbetaII activation by 1-beta-D-arabinofuranosylcytosine is antagonistic to stimulation of apoptosis and Bcl-2alpha down-regulation. J Biol Chem. 1997 Sep 19;272(38):23481-4. doi: 10.1074/jbc.272.38.23481.
16	Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
17	Reversible epigenetic regulation of 14-3-3 expression in acquired gemcitabine resistance by uhrf1 and DNA methyltransferase 1. Mol Pharmacol. 2014 Nov;86(5):561-9. doi: 10.1124/mol.114.092544. Epub 2014 Sep 4.
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23	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
24	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
25	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
26	Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
27	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
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29	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
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31	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
32	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
33	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
34	Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
35	Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
36	Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
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