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]
Therapeutic Class
Anti-HIV Agents
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) 2
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 3
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]
⏷ 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
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]

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]

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]

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]
Molecular Interaction Atlas (MIA) 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]
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]
⏷ 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
⏷ 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
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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.
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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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19 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
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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]
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25 MHRA. Medicines and Healthcare Products Regulatory Agency "Orlistat: theoretical interaction with antiretroviral HIV medicines.".