Details of the Drug

General Information of Drug (ID: DMH7MUV)

Drug Name

Zalcitabine

Synonyms

zalcitabine; Dideoxycytidine; 7481-89-2; 2',3'-DIDEOXYCYTIDINE; ddCyd; HIVID; ddC; Cytidine, 2',3'-dideoxy-; Zalcitibine; 4-Amino-1-((2R,5S)-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one; 2,3-dideoxycytidine; NSC 606170; UNII-6L3XT8CB3I; CCRIS 692; HSDB 7156; C9H13N3O3; Ro-24-2027/000; Ro 24-2027/000; CHEMBL853; BRN 0654956; 6L3XT8CB3I; CHEBI:10101; 1-(2,3-Dideoxy-beta-D-ribofuranosyl)cytosine; WREGKURFCTUGRC-POYBYMJQSA-N; 4-amino-1-[(2R,5S)-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1H)-one; MFCD00012188; DdC; DdCyd; D 5782; DDC (DDC); DdC & Interferon alpha; DdC & sCD4; DdC (Antiviral); Hivid (TN); Hivid(TM); Interferon AD + ddC; KS-1130; SRI-7707; Beta-D-DDC; DS-4152 & ddC; DdC & GM-CSF; DdC & IFN-alpha; DdC & NP (from PHCA or HSA); PC-SOD & ddC; Zalcitabine [USAN:INN:BAN]; Hivid, Dideoxycytidine, NSC 606170, Zalcitabine; Zalcitabine (JAN/USP/INN); Beta-D-2',3'-Dideoxycytidine; Cytidine, 2',3'-dideoxy & Interferon alpha; Sulfated polysaccharide-peptidoglycan DS-4152 & 2',3'-Dideoxycytidine; Cytidine, 2',3'-dideoxy-& Colony-stimulating factor; Beta-D-2',3'-Dideoxycytidine & Granulocyte-macrophage colony-stimulating factor; Lecithinized superoxide dismutase & beta-D-2',3'-Dideoxycytidine; 2',3'-Dideoxycytidine & Interferon-alpha; 2',3'-Dideoxycytidine & Nanoparticles (from human serum albumin or polyhexylcyanoacrylate); 2',3'-Dideoxycytidine & sCD4(soluble recombinant protein); 3'-Azido-3'-deoxythymidine/2',3'-Dideoxycytidine; 4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one; DdC

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[1]
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Therapeutic Class

Anti-HIV Agents

Affected Organisms

Human Immunodeficiency Virus

ATC Code

J05AF03: Zalcitabine

J05AF: Nucleoside and nucleotide reverse transcriptase inhibitors

J05A: DIRECT ACTING ANTIVIRALS

J05: ANTIVIRALS FOR SYSTEMIC USE

J: ANTIINFECTIVES FOR SYSTEMIC USE

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

211.22

Logarithm of the Partition Coefficient (xlogp)

-1.3

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
Bioavailability: The bioavailability of drug is 80% []
Clearance: The drug present in the plasma can be removed from the body at the rate of 5.6 mL/min/kg [3]
Elimination: 65% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 2 hours [3]
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 0.1522 micromolar/kg/day [4]
Unbound Fraction: The unbound fraction of drug in plasma is 0.96% [3]
Vd: The volume of distribution (Vd) of drug is 0.304-0.734 L/kg []
Water Solubility: The ability of drug to dissolve in water is measured as 76.4 mg/mL [2]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Cardiac disorders	Not Available	CYB5R1	OTMDHMLA	[5]
Cardiotoxicity	Not Available	TPI1	OT14KP4B	[5]
Cardiotoxicity	Not Available	PARP1	OT310QSG	[5]
Cardiotoxicity	Not Available	HSPA12A	OTFOCDD6	[5]
Cardiotoxicity	Not Available	HSPA5	OTFUIRAO	[5]
Cardiotoxicity	Not Available	DES	OTI09KBW	[5]
Cardiotoxicity	Not Available	MB	OTYWYL2D	[5]
Cell-mediated cytotoxicity	Not Available	SDS	OT5WTJ2M	[5]
Cell-mediated cytotoxicity	Not Available	COX4I1	OTU0FC24	[5]
Cytogenetic abnormality	Not Available	POLRMT	OT5Q8ZUJ	[5]
Neoplasm	Not Available	TP53	OTIE1VH3	[5]
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⏷ Show the Full List of 11 ADR Information of This Drug

Chemical Identifiers

Formula: C9H13N3O3
IUPAC Name: 4-amino-1-[(2R,5S)-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
Canonical SMILES: C1C[C@@H](O[C@@H]1CO)N2C=CC(=NC2=O)N
InChI: InChI=1S/C9H13N3O3/c10-7-3-4-12(9(14)11-7)8-2-1-6(5-13)15-8/h3-4,6,8,13H,1-2,5H2,(H2,10,11,14)/t6-,8+/m0/s1
InChIKey: WREGKURFCTUGRC-POYBYMJQSA-N

Cross-matching ID

PubChem CID: 24066
ChEBI ID: CHEBI:10101
CAS Number: 7481-89-2
UNII: 6L3XT8CB3I
DrugBank ID: DB00943
TTD ID: D0Z9QR
VARIDT ID: DR00175
INTEDE ID: DR1724
ACDINA ID: D01531

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[6]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 8 (ABCC11)	DTWN7FC	ABCCB_HUMAN	Substrate	[7]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[8]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[9]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[9]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Substrate	[9]
Cytochrome P450 3A43 (CYP3A43)	DEO1IE3	CP343_HUMAN	Substrate	[9]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Drug Response	[5]
Cytochrome c oxidase subunit 1 (COX1)	OTG3O9BN	COX1_HUMAN	Gene/Protein Processing	[11]
Cytochrome c oxidase subunit 3 (COX3)	OTNNGBYJ	COX3_HUMAN	Gene/Protein Processing	[12]
Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (COX4I1)	OTU0FC24	COX41_HUMAN	Drug Response	[5]
Deoxycytidine kinase (DCK)	OTW8HLZC	DCK_HUMAN	Drug Response	[13]
Desmin (DES)	OTI09KBW	DESM_HUMAN	Drug Response	[5]
DNA repair nuclease/redox regulator APEX1 (APEX1)	OT53OI14	APEX1_HUMAN	Drug Response	[14]
DNA-directed RNA polymerase, mitochondrial (POLRMT)	OT5Q8ZUJ	RPOM_HUMAN	Drug Response	[5]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Drug Response	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Zalcitabine

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Zalcitabine caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[15]
Etravirine	DMGV8QU	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Etravirine.	Human immunodeficiency virus disease [1C60-1C62]	[16]
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Coadministration of a Drug Treating the Disease Different from Zalcitabine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Zalcitabine and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[15]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Zalcitabine and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[17]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Zalcitabine and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[18]
Eribulin	DM1DX4Q	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Eribulin.	Breast cancer [2C60-2C6Y]	[16]
Ixabepilone	DM2OZ3G	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Ixabepilone.	Breast cancer [2C60-2C6Y]	[16]
Cabazitaxel	DMPAZHC	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Cabazitaxel.	Breast cancer [2C60-2C6Y]	[16]
Trastuzumab Emtansine	DMU1LXS	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Trastuzumab Emtansine.	Breast cancer [2C60-2C6Y]	[16]
Atorvastatin	DMF28YC	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Atorvastatin.	Cardiovascular disease [BA00-BE2Z]	[16]
Polatuzumab vedotin	DMF6Y0L	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Polatuzumab vedotin.	Diffuse large B-cell lymphoma [2A81]	[16]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Zalcitabine and Cannabidiol.	Epileptic encephalopathy [8A62]	[19]
Colchicine	DM2POTE	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Colchicine.	Gout [FA25]	[16]
Isoniazid	DM5JVS3	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Isoniazid.	HIV-infected patients with tuberculosis [1B10-1B14]	[16]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[16]
Fluvastatin	DM4MDJY	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Fluvastatin.	Hyper-lipoproteinaemia [5C80]	[16]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Zalcitabine and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[20]
Rosuvastatin	DMMIQ7G	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Rosuvastatin.	Hyper-lipoproteinaemia [5C80]	[16]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Zalcitabine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[21]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Zalcitabine and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[22]
Hydralazine	DMU8JGH	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Hydralazine.	Hypertension [BA00-BA04]	[16]
Auranofin	DMWE2N4	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Auranofin.	Inflammatory arthropathy [FA2Z]	[16]
Nelarabine	DMB6VEG	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Nelarabine.	Leukaemia [2A60-2B33]	[16]
Crizotinib	DM4F29C	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Crizotinib.	Lung cancer [2C25]	[16]
Hydroxychloroquine	DMSIVND	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Hydroxychloroquine.	Malaria [1F40-1F45]	[16]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Zalcitabine and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[23]
Fludarabine	DMVRLT7	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Fludarabine.	Malignant haematopoietic neoplasm [2B33]	[16]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Zalcitabine and Idelalisib.	Mature B-cell leukaemia [2A82]	[24]
Ponatinib	DMYGJQO	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Ponatinib.	Mature B-cell lymphoma [2A85]	[16]
Ipilimumab	DMJTIYK	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Ipilimumab.	Melanoma [2C30]	[16]
Carfilzomib	DM48K0X	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Carfilzomib.	Multiple myeloma [2A83]	[16]
Thalidomide	DM70BU5	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Thalidomide.	Multiple myeloma [2A83]	[16]
Elotuzumab	DMEYHG9	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Elotuzumab.	Multiple myeloma [2A83]	[16]
Orlistat	DMRJSP8	Moderate	Altered absorption of Zalcitabine caused by Orlistat.	Obesity [5B80-5B81]	[25]
Carboplatin	DMG281S	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Carboplatin.	Ovarian cancer [2C73]	[16]
Levodopa	DMN3E57	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Levodopa.	Parkinsonism [8A00]	[16]
Tocilizumab	DM7J6OR	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Tocilizumab.	Rheumatoid arthritis [FA20]	[16]
Golimumab	DMHZV7X	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Golimumab.	Rheumatoid arthritis [FA20]	[16]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Zalcitabine and Leflunomide.	Rheumatoid arthritis [FA20]	[21]
Docetaxel	DMDI269	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Docetaxel.	Solid tumour/cancer [2A00-2F9Z]	[16]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Zalcitabine and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[19]
Taxol	DMUOT9V	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Taxol.	Solid tumour/cancer [2A00-2F9Z]	[16]
Pomalidomide	DMTGBAX	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Pomalidomide.	Systemic sclerosis [4A42]	[16]
Amiodarone	DMUTEX3	Moderate	Increased risk of peripheral neuropathy by the combination of Zalcitabine and Amiodarone.	Ventricular tachyarrhythmia [BC71]	[16]
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⏷ Show the Full List of 42 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium	E00625	Not Available	Disintegrant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 7 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Zalcitabine 0.375mg tablet	0.375mg	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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: 4828).
2	BDDCS applied to over 900 drugs
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	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
5	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
6	A peptide inhibitor of HIV-1 reverse transcriptase using alpha,beta-dehydro residues: a structure-based computer model. J Biomol Struct Dyn. 1998 Oct;16(2):347-54.
7	MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine. J Biol Chem. 2003 Aug 8;278(32):29509-14.
8	Interaction of zalcitabine with human organic anion transporter 1. Pharmazie. 2006 May;61(5):491-2.
9	Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. Clin Pharmacokinet. 1997 Mar;32(3):194-209.
10	Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
11	Assessment of mitochondrial toxicity by analysis of mitochondrial protein expression in mononuclear cells. Cytometry B Clin Cytom. 2009 May;76(3):181-90. doi: 10.1002/cyto.b.20458.
12	Small-scale immunopurification of cytochrome c oxidase for a high-throughput multiplexing analysis of enzyme activity and amount. Biotechnol Appl Biochem. 2007 Dec;48(Pt 4):167-78. doi: 10.1042/BA20060223.
13	Molecular basis of 2',3'-dideoxycytidine-induced drug resistance in human cells. Mol Cell Biochem. 2002 Feb;231(1-2):173-7. doi: 10.1023/a:1014441209108.
14	A dominant-negative form of the major human abasic endonuclease enhances cellular sensitivity to laboratory and clinical DNA-damaging agents. Mol Cancer Res. 2007 Jan;5(1):61-70. doi: 10.1158/1541-7786.MCR-06-0329.
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16	Argov Z, Mastaglia FL "Drug-induced peripheral neuropathies." Br Med J 1 (1979): 663-6. [PMID: 219931]
17	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
18	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
19	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
20	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
21	Canadian Pharmacists Association.
22	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
23	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]
24	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
25	MHRA. Medicines and Healthcare Products Regulatory Agency "Orlistat: theoretical interaction with antiretroviral HIV medicines.".