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]
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Therapeutic Class

Anticancer 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)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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: CHEBI:94701
CAS Number: 21679-14-1
DrugBank ID: DB01073
TTD ID: D0F2XQ
VARIDT ID: DR00434

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
Adenosine deaminase (ADA)	TTLP57V	ADA_HUMAN	Inhibitor	[6]

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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]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Gene/Protein Processing	[9]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Gene/Protein Processing	[9]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[10]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[11]
DNA cytosine-5)-methyltransferase 1 (DNMT1)	OTM2DGTK	DNMT1_HUMAN	Gene/Protein Processing	[12]
Dual specificity mitogen-activated protein kinase kinase 1 (MAP2K1)	OT4Y9NQI	MP2K1_HUMAN	Gene/Protein Processing	[13]
Dual specificity mitogen-activated protein kinase kinase 2 (MAP2K2)	OTUE7Z91	MP2K2_HUMAN	Gene/Protein Processing	[13]
Growth/differentiation factor 15 (GDF15)	OTWQN50N	GDF15_HUMAN	Gene/Protein Processing	[11]

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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 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]	[14]
Ofloxacin	DM0VQN3	Minor	Decreased absorption of Fludarabine due to intestinal mucosa variation caused by Ofloxacin.	Bacterial infection [1A00-1C4Z]	[15]
Sparfloxacin	DMB4HCT	Minor	Decreased absorption of Fludarabine due to intestinal mucosa variation caused by Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[15]
Gemifloxacin	DMHT34O	Minor	Decreased absorption of Fludarabine due to intestinal mucosa variation caused by Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[15]
ABT-492	DMJFD2I	Minor	Decreased absorption of Fludarabine due to intestinal mucosa variation caused by ABT-492.	Bacterial infection [1A00-1C4Z]	[15]
Levofloxacin	DMS60RB	Minor	Decreased absorption of Fludarabine due to intestinal mucosa variation caused by Levofloxacin.	Bacterial infection [1A00-1C4Z]	[15]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of peripheral neuropathy by the combination of Fludarabine and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[16]
Teriflunomide	DMQ2FKJ	Major	Additive myelosuppressive effects by the combination of Fludarabine and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[17]
Denosumab	DMNI0KO	Moderate	Additive myelosuppressive effects by the combination of Fludarabine and Denosumab.	Low bone mass disorder [FB83]	[18]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Fludarabine and Tecfidera.	Multiple sclerosis [8A40]	[19]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Fludarabine and Siponimod.	Multiple sclerosis [8A40]	[20]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Fludarabine and Fingolimod.	Multiple sclerosis [8A40]	[21]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Fludarabine and Ocrelizumab.	Multiple sclerosis [8A40]	[22]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Fludarabine and Ozanimod.	Multiple sclerosis [8A40]	[14]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive myelosuppressive effects by the combination of Fludarabine and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[23]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Fludarabine and Canakinumab.	Rheumatoid arthritis [FA20]	[24]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Fludarabine and Rilonacept.	Rheumatoid arthritis [FA20]	[24]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Fludarabine and Golimumab.	Rheumatoid arthritis [FA20]	[25]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Fludarabine when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[26]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Fludarabine and Valganciclovir.	Virus infection [1A24-1D9Z]	[20]
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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	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.
10	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.
11	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.
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	The histone deacetylase inhibitor MS-275 interacts synergistically with fludarabine to induce apoptosis in human leukemia cells. Cancer Res. 2004 Apr 1;64(7):2590-600. doi: 10.1158/0008-5472.can-03-2631.
14	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
15	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]
16	Carrion C, Espinosa E, Herrero A, Garcia B "Possible vincristine-isoniazid interaction." Ann Pharmacother 29 (1995): 201. [PMID: 7756727]
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]