Details of the Drug

General Information of Drug (ID: DMVRLT7)

Drug Name
Fludarabine
Synonyms
FaraA; Fludarabina; Fludarabinum; Fluradosa; Fludarabina [Spanish]; Fludarabine [INN]; Fludarabinum [Latin]; SQ Fludarabine; Fludara, Fludarabine; Fludarabine (INN); Fluradosa (TN); F-Ara-A; (2R,3S,4S,5R)-2-(6-amino-2-fluoro-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol; (2R,3S,4S,5R)-2-(6-amino-2-fluoropurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol; 2-F-ara-A; 2-Fluoro Ara-A; 2-Fluoro-9-beta-D-arabinofuranosyladenine; 9-beta-D-Arabinofuranosyl-2-fluoroadenine; 9-beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine; 9H-Purin-6-amine, 9-beta-D-arabinofuranosyl-2-fluoro-(9CI)
Indication
Disease Entry ICD 11 Status REF
Acute myelogenous leukaemia 2A41 Approved [1]
Cutaneous melanoma 2C30 Approved [1]
Haematological malignancy 2B33.Y Approved [2]
Hematologic disease 3C0Z Approved [1]
Hepatosplenic T-cell lymphoma N.A. Approved [1]
Immunodeficiency 4A00-4A85 Approved [1]
Large granular lymphocytic leukemia 2A90.1 Approved [1]
Lung cancer 2C25.0 Approved [1]
MALT lymphoma N.A. Approved [1]
Multiple sclerosis 8A40 Approved [1]
Myeloproliferative neoplasm 2A20 Approved [1]
Nodal marginal zone lymphoma 2A85.0 Approved [1]
Primary cutaneous peripheral T-cell lymphoma not otherwise specified N.A. Approved [1]
Recurrent adult burkitt lymphoma 2A85.6 Approved [1]
Small intestine lymphoma N.A. Approved [1]
Splenic marginal zone lymphoma N.A. Approved [1]
Systemic lupus erythematosus 4A40.0 Approved [1]
Systemic sclerosis 4A42 Approved [1]
Testicular lymphoma N.A. Approved [1]
Classic Hodgkin lymphoma N.A. Investigative [1]
Colon cancer 2B90.Z Investigative [1]
Gastric cancer 2B72 Investigative [1]
Neuroblastoma 2D11.2 Investigative [1]
⏷ Show the Full List of Indication(s)
Therapeutic Class
Anticancer Agents
Affected Organisms
Humans and other mammals
ATC Code
L01BB05: Fludarabine
L01BB: Purine analogues
L01B: ANTIMETABOLITES
L01: ANTINEOPLASTIC AGENTS
L: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 285.23
Logarithm of the Partition Coefficient (xlogp) -0.6
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 9
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [3]
Bioavailability
The bioavailability of drug is 55% []
Half-life
The concentration or amount of drug in body reduced by one-half in 20 hours [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 2.6598 micromolar/kg/day [5]
Water Solubility
The ability of drug to dissolve in water is measured as 3.53 mg/mL [3]
Chemical Identifiers
Formula
C10H12FN5O4
IUPAC Name
(2R,3S,4S,5R)-2-(6-amino-2-fluoropurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
Canonical SMILES
C1=NC2=C(N=C(N=C2N1[C@H]3[C@H]([C@@H]([C@H](O3)CO)O)O)F)N
InChI
InChI=1S/C10H12FN5O4/c11-10-14-7(12)4-8(15-10)16(2-13-4)9-6(19)5(18)3(1-17)20-9/h2-3,5-6,9,17-19H,1H2,(H2,12,14,15)/t3-,5-,6+,9-/m1/s1
InChIKey
HBUBKKRHXORPQB-FJFJXFQQSA-N
Cross-matching ID
PubChem CID
657237
ChEBI ID
CHEMBL1568
CAS Number
21679-14-1
UNII
P2K93U8740
DrugBank ID
DB01073
TTD ID
D0F2XQ
VARIDT ID
DR00434
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Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Adenosine deaminase (ADA) TTLP57V ADA_HUMAN Inhibitor [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Gene/Protein Processing [7]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Gene/Protein Processing [8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Gene/Protein Processing [9]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Gene/Protein Processing [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [11]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [11]
Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN) OTOWDUNT PTEN_HUMAN Gene/Protein Processing [12]
Tumor necrosis factor receptor superfamily member 10A (TNFRSF10A) OTBPCU2O TR10A_HUMAN Gene/Protein Processing [13]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B) OTA1CPBV TR10B_HUMAN Gene/Protein Processing [14]
Tumor necrosis factor receptor superfamily member 6 (FAS) OTP9XG86 TNR6_HUMAN Gene/Protein Processing [15]
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 Disease Different from Fludarabine (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Roflumilast DMPGHY8 Moderate Additive immunosuppressive effects by the combination of Fludarabine and Roflumilast. Asthma [CA23] [16]
Ofloxacin DM0VQN3 Minor Decreased absorption of Fludarabine due to intestinal mucosa variation caused by Ofloxacin. Bacterial infection [1A00-1C4Z] [17]
Sparfloxacin DMB4HCT Minor Decreased absorption of Fludarabine due to intestinal mucosa variation caused by Sparfloxacin. Bacterial infection [1A00-1C4Z] [17]
Gemifloxacin DMHT34O Minor Decreased absorption of Fludarabine due to intestinal mucosa variation caused by Gemifloxacin. Bacterial infection [1A00-1C4Z] [17]
ABT-492 DMJFD2I Minor Decreased absorption of Fludarabine due to intestinal mucosa variation caused by ABT-492. Bacterial infection [1A00-1C4Z] [17]
Levofloxacin DMS60RB Minor Decreased absorption of Fludarabine due to intestinal mucosa variation caused by Levofloxacin. Bacterial infection [1A00-1C4Z] [17]
Brentuximab vedotin DMWLC57 Moderate Increased risk of peripheral neuropathy by the combination of Fludarabine and Brentuximab vedotin. Hodgkin lymphoma [2B30] [18]
Teriflunomide DMQ2FKJ Major Additive myelosuppressive effects by the combination of Fludarabine and Teriflunomide. Hyper-lipoproteinaemia [5C80] [19]
Denosumab DMNI0KO Moderate Additive myelosuppressive effects by the combination of Fludarabine and Denosumab. Low bone mass disorder [FB83] [20]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Fludarabine and Tecfidera. Multiple sclerosis [8A40] [21]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Fludarabine and Siponimod. Multiple sclerosis [8A40] [22]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Fludarabine and Fingolimod. Multiple sclerosis [8A40] [23]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Fludarabine and Ocrelizumab. Multiple sclerosis [8A40] [24]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Fludarabine and Ozanimod. Multiple sclerosis [8A40] [16]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive myelosuppressive effects by the combination of Fludarabine and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [25]
Canakinumab DM8HLO5 Moderate Additive immunosuppressive effects by the combination of Fludarabine and Canakinumab. Rheumatoid arthritis [FA20] [26]
Rilonacept DMGLUQS Moderate Additive immunosuppressive effects by the combination of Fludarabine and Rilonacept. Rheumatoid arthritis [FA20] [26]
Golimumab DMHZV7X Major Additive immunosuppressive effects by the combination of Fludarabine and Golimumab. Rheumatoid arthritis [FA20] [27]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Fludarabine when combined with Anthrax vaccine. Sepsis [1G40-1G41] [28]
Valganciclovir DMS2IUH Moderate Additive myelosuppressive effects by the combination of Fludarabine and Valganciclovir. Virus infection [1A24-1D9Z] [22]
⏷ Show the Full List of 20 DDI Information of This Drug

References

1 Fludarabine 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: 4802).
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
6 Purine nucleoside analogs in indolent non-Hodgkin's lymphoma. Oncology (Williston Park). 2000 Jun;14(6 Suppl 2):13-5.
7 MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells. Blood. 2006 May 15;107(10):4109-14. doi: 10.1182/blood-2005-08-3273. Epub 2006 Jan 26.
8 Matrix metalloproteinase-9 is involved in chronic lymphocytic leukemia cell response to fludarabine and arsenic trioxide. PLoS One. 2014 Jun 23;9(6):e99993. doi: 10.1371/journal.pone.0099993. eCollection 2014.
9 Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006 May 15;107(10):4122-9. doi: 10.1182/blood-2005-11-4465. Epub 2006 Jan 26.
10 Role of histone deacetylase inhibitor-induced reactive oxygen species and DNA damage in LAQ-824/fludarabine antileukemic interactions. Mol Cancer Ther. 2008 Oct;7(10):3285-97. doi: 10.1158/1535-7163.MCT-08-0385.
11 9-beta-D-arabinofuranosyl-2-fluoroadenine inhibits expression of vascular endothelial growth factor through hypoxia-inducible factor-1 in human ovarian cancer cells. Mol Pharmacol. 2004 Jul;66(1):178-86. doi: 10.1124/mol.66.1.178.
12 Comparative effects of retinoic acid, vitamin D and resveratrol alone and in combination with adenosine analogues on methylation and expression of phosphatase and tensin homologue tumour suppressor gene in breast cancer cells. Br J Nutr. 2012 Mar;107(6):781-90. doi: 10.1017/S0007114511003631. Epub 2011 Aug 1.
13 Role of the TRAIL/APO2-L death receptors in chlorambucil- and fludarabine-induced apoptosis in chronic lymphocytic leukemia. Oncogene. 2003 Nov 13;22(51):8356-69. doi: 10.1038/sj.onc.1207004.
14 Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells. J Cell Biochem. 2008 May 15;104(2):595-605. doi: 10.1002/jcb.21649.
15 Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation. Blood. 2001 Nov 1;98(9):2800-7. doi: 10.1182/blood.v98.9.2800.
16 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
17 Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
18 Carrion C, Espinosa E, Herrero A, Garcia B "Possible vincristine-isoniazid interaction." Ann Pharmacother 29 (1995): 201. [PMID: 7756727]
19 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
20 Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
21 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
22 Cerner Multum, Inc. "Australian Product Information.".
23 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
24 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
25 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
26 Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
27 Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
28 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]