FLUDARABINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H12FN5O4
Molecular Weight	285.2318
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(F)=NC2=C1N=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3O

InChI

InChIKey=HBUBKKRHXORPQB-FJFJXFQQSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022137lbl.pdf

Fludarabine or fludarabine phosphate is a chemotherapy drug used in the treatment of hematological malignancies (cancers of blood cells such as leukemias and lymphomas). It is a purine analog, which interferes with DNA synthesis. Fludarabine phosphate is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-β-D-arabinofuranosyladenine (ara-A), that is relatively resistant to deamination by adenosine deaminase. Fludarabine (marketed as fludarabine phosphate under the trade name Fludara) is a chemotherapy drug used in the treatment of hematological malignancies. Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA polymerase alpha subunit 9 Target ID: CHEMBL1828 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022137lbl.pdf	Inhibitor 8297
Ribonucleoside-diphosphate reductase M1 chain 4 Target ID: CHEMBL1830 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=23115527	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic lymphocytic leukemia 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022137lbl.pdf	Primary		Approved 8429	FLUDARABINE PHOSPHATE Approved Use Fludarabine Phosphate Injection is indicated for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating-agent containing regimen. The safety and effectiveness of Fludarabine Phosphate Injection in previously untreated or non-refractory patients with CLL have not been established. Important Limitations Fludarabine Phosphate Injection should not be used in patients with severe renal impairment (creatinine clearance less than 30 mL/min/1.73 m2). Launch Date 2007

C_max

Value	Dose	Co-administered	Analyte	Population
4.28 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17211431	30 mg/m² single, intravenous dose: 30 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		FLUDARABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
21.55 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17211431	30 mg/m² single, intravenous dose: 30 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		FLUDARABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/17211431	30 mg/m² single, intravenous dose: 30 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		FLUDARABINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
20 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020038s033lbl.pdf	25 mg/m² 1 times / day multiple, intravenous dose: 25 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		FLUDARABINE plasma	Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg/m2 1 times / day multiple, intravenous Highest studied dose Dose: 100 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 100 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2428488	unhealthy, 32 years (range: 19-59 years) n = 2 Health Status: unhealthy Condition: Acute Leukemia Age Group: 32 years (range: 19-59 years) Sex: M+F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/2428488	Other AEs: Leukopenia... Other AEs: Leukopenia (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/2428488
40 mg/m2 1 times / day steady, intravenous MTD Dose: 40 mg/m2, 1 times / day Route: intravenous Route: steady Dose: 40 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2428488	unhealthy, 32 years (range: 19-59 years) n = 11 Health Status: unhealthy Condition: Acute Leukemia Age Group: 32 years (range: 19-59 years) Sex: M+F Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/2428488	Sources: https://pubmed.ncbi.nlm.nih.gov/2428488
20 mg/m2 1 times / day multiple, intravenous MTD Dose: 20 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 20 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2452888	unhealthy, 55 years (range: 26-78 years) Health Status: unhealthy Age Group: 55 years (range: 26-78 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/2452888	Sources: https://pubmed.ncbi.nlm.nih.gov/2452888
45 mg/m2 1 times / day multiple, intravenous Dose: 45 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 45 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2452888	unhealthy, 55 years (range: 26-78 years) n = 1 Health Status: unhealthy Age Group: 55 years (range: 26-78 years) Sex: M+F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2452888	DLT: Myelosuppression... Dose limiting toxicities: Myelosuppression (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/2452888
40 mg/m2 1 times / day steady, oral Recommended Dose: 40 mg/m2, 1 times / day Route: oral Route: steady Dose: 40 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_MedR.pdf Page: p. 61	unhealthy, 64 years (range: 30-75 years) n = 81 Health Status: unhealthy Age Group: 64 years (range: 30-75 years) Sex: M+F Population Size: 81 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_MedR.pdf Page: p. 61	Disc. AE: Thrombocytopenia, Anemia hemolytic autoimmune... AEs leading to discontinuation/dose reduction: Thrombocytopenia (1 patient) Anemia hemolytic autoimmune (3 patients) Pneumonia (1 patient) Anemia (1 patient) Foot drop (1 patient) Sepsis (1 patient) Bronchitis (1 patient) Rash (1 patient) Face edema (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_MedR.pdf Page: p. 61
25 mg/m2 1 times / day steady, intravenous Recommended Dose: 25 mg/m2, 1 times / day Route: intravenous Route: steady Dose: 25 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022137lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: B-cell chronic lymphocytic leukemia Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022137lbl.pdf	Other AEs: CNS toxicity, Hemolytic anemia... Other AEs: CNS toxicity Hemolytic anemia Pulmonary toxicity Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/022137lbl.pdf
40 mg/m2 1 times / day steady, oral Recommended Dose: 40 mg/m2, 1 times / day Route: oral Route: steady Dose: 40 mg/m2, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022273lbl.pdf	unhealthy, adult Health Status: unhealthy Condition: B-cell chronic lymphocytic leukemia Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022273lbl.pdf	Other AEs: CNS toxicity, Hemolytic anemia... Other AEs: CNS toxicity Hemolytic anemia Pulmonary toxicity Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022273lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882	P-gp 1537 CYP1A2 1054

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=47 Page: 47.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=47 Page: 47.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=47 Page: 47.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=47 Page: 47.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=47 Page: 47.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=47 Page: 47.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=47 Page: 47.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=27 Page: 27.0	no

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=41 Page: 41.0	no
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=41 Page: 41.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022273s000_ClinPharmR.pdf#page=27 Page: 27.0	weak

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-0955	http://www.3bsc.com/index/pro_info.php?id=41860
AA Blocks	AA0039N2	https://www.aablocks.com/goods/Goods/detail?id=AA0039N2
AEchem Scientific Corp., USA	AE1-015944	http://www.aechemsc.com/info_products/AE1-015944.php
AHH Chemical co.,ltd	MT-51811	http://www.ahhchemical.com/product/MT-51811.html
Aaron Chemicals	AR003AEU	http://www.aaronchem.com/21679-14-1
AbMole Bioscience	M2028	http://www.abmole.com/products/fludarabine.html
Achemo Scientific Limited	AC-15243	http://www.achemo.com/search/?Keyword= 21679-14-1
Achemtek	0104-023119	http://www.achemtek.com/21679-14-1
Active Biopharma	ABP000557	http://www.activebiopharma.com/21679-14-1
Allbio Pharm Co., Ltd	AD08014	http://www.allbiopharm.com/product/n/AD08014
AstaTech, Inc.	HG1007	http://www.astatechinc.com/CPSResult.php?CRNO=17780
Aurora Fine Chemicals LLC	A24.077.320	http://online.aurorafinechemicals.com/info?ID=A24.077.320
Aurora Fine Chemicals LLC	K16.603.080	http://online.aurorafinechemicals.com/info?ID=K16.603.080
Aurum Pharmatech LLC	S-6059	http://www.Aurumpharmatech.com/Product/ProductDetails/S_6059
AvaChem Scientific	2653	http://www.avachem.com/productSearch.asp?2653
Avantor Inc	100576-076	https://us.vwr.com/store/catalog/product.jsp?catalog_number=100576-076
BLD Pharm	BD11972	http://www.bldpharm.com/products/21679-14-1.html
BioChemPartner	BCP01383	http://www.biochempartner.com/21679-14-1-BCP01383
BioCrick	BCC2518	http://www.biocrick.com/Fludarabine-BCC2518.html
BroadPharm	BP-25389	https://www.broadpharm.com/web/product.php?catalog=BP-25389
CSNpharm	CSN10528	https://www.csnpharm.com/products/fludarabine.html
Chem Scene	CS-2133	http://www.chemscene.com/21679-14-1.html
ChemMol	97900454	http://www.chemmol.com/chemmol/97900454.html
Chemspace	CSSB00000743926	https://chem-space.com/CSSB00000743926
Combi-Blocks	QA-3101	http://www.combi-blocks.com/cgi-bin/find.cgi?QA-3101
DC Chemicals	DC5889	http://www.dcchemicals.com/product_show-Fludarabine.html
Enamine	Z802671516	https://www.enaminestore.com/catalog/Z802671516
Excenen	EX-A833	http://www.excenen.com/searchresultlist.php?id=21679-14-1
Glentham Life Sciences	GP0730	http://www.glentham.com/products/product/GP0730/
Hairui	HR129788	http://www.hairuichem.com/en/product/21679-14-1.html
Lab Network	LN00175758	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00175758
Matrix Scientific	76060	https://www.matrixscientific.com/076060.html
MedChem Express	HY-B0069	https://www.medchemexpress.com/fludarabine.html
MuseChem	A001054	https://www.musechem.com/product/A001054.html
OChem	2832	http://www.ocheminc.com/index.php?act=psearch&pid=679F141
Oakwood	79410	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=64584&ExtHyperLink=1
Parchem	28968	http://www.parchem.com/chemical-supplier-distributor/Fludarabine-018968.aspx
Selleck Chemicals	S1491	http://www.selleckchem.com/products/Fludarabine(Fludara).html
Sigma-Aldrich	F2773_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/f2773?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S528115	http://www.smolecule.com/products/s528115
Synblock Inc	SB19413	http://www.synblock.com/product/21679-14-1.html
Synchem UG and Co KG	67378	http://www.synchem.de/chemical_Fludarabine.html
THE BioTek	bt-268280	https://www.thebiotek.com/product/inhibitors/bt-268280
Tocris	3495	https://www.tocris.com/products/fludarabine_3495
VladaChem	VL281192-10MG	https://www.vladachem.com/product.php?products=21679-14-1
abcr GmbH	AB348142	http://www.abcr.com/shop/en/AB348142
eNovation Chemicals	D481187	http://www.enovationchem.com/productDetails.asp?productID=D481187
eNovation Chemicals	D961702	https://www.enovationchem.com/ProductDetails.asp?ProductID=D961702
eNovation Chemicals	Y0974205	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0974205
iChemical	EBD18913	http://www.ichemical.com/products/21679-14-1.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-2497721739	https://mcule.com/MCULE-2497721739/

PubMed

Title	Date	PubMed
In vitro biological activity of 9-beta-D-arabinofuranosyl-2-fluoroadenine and the biochemical actions of its triphosphate on DNA polymerases and ribonucleotide reductase from HeLa cells.	1982 Mar	7048062
Fludarabine and arabinosylcytosine therapy of refractory and relapsed acute myelogenous leukemia.	1993 Mar	8394169
Apoptosis induction with three nucleoside analogs on freshly isolated B-chronic lymphocytic leukemia cells.	1994 Dec	7977303
Fludarabine + Ara-C + G-CSF: cytotoxic effect and induction of apoptosis on fresh acute myeloid leukemia cells.	1994 Dec	7528855
Increased p21/WAF-1 and p53 protein levels following sequential three drug combination regimen of fludarabine, cytarabine and docetaxel induces apoptosis in human leukemia cells.	1998 Jul-Aug	9703875
Activation of a p53-mediated apoptotic pathway in quiescent lymphocytes after the inhibition of DNA repair by fludarabine.	2003 Aug 1	12912974
Down-regulation of deoxycytidine kinase in human leukemic cell lines resistant to cladribine and clofarabine and increased ribonucleotide reductase activity contributes to fludarabine resistance.	2003 Jan 15	12504799
Cytotoxic drugs enhance the ex vivo sensitivity of malignant cells from a subset of acute myeloid leukaemia patients to apoptosis induction by tumour necrosis factor receptor-related apoptosis-inducing ligand.	2003 Jun	12780785
Drug-loaded red blood cell-mediated clearance of HIV-1 macrophage reservoir by selective inhibition of STAT1 expression.	2003 Nov	12960277
Fatal peripheral neuropathy following FLA chemotherapy.	2004 Aug	15279668
Adenine deoxynucleotides fludarabine and cladribine induce apoptosis in a CD95/Fas receptor, FADD and caspase-8-independent manner by activation of the mitochondrial cell death pathway.	2004 Dec 16	15516989
Post-transcriptional regulation of inducible nitric oxide synthase in chronic lymphocytic leukemia B cells in pro- and antiapoptotic culture conditions.	2004 Jan	14574328
A phase I and pharmacodynamic study of fludarabine, carboplatin, and topotecan in patients with relapsed, refractory, or high-risk acute leukemia.	2004 Oct 15	15501959
Recurrent chemotherapy-induced tumor lysis syndrome (TLS) with renal failure in a patient with chronic lymphocytic leukemia - successful treatment and prevention of TLS with low-dose rasburicase.	2005 Dec	16313266
Inhibition of the PI3K pathway sensitizes fludarabine-induced apoptosis in human leukemic cells through an inactivation of MAPK-dependent pathway.	2005 Jun 3	15850772
Alteration of DNA methylation status in K562 and MCF-7 cancer cell lines by nucleoside analogues.	2006	17065059
Chronic lymphocytic leukaemia, synchronous small cell carcinoma and squamous neoplasia of the urinary bladder in a paraplegic man following long-term phenoxybenzamine therapy.	2006 Mar	16130025
MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells.	2006 May 15	16439685
Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL).	2006 May 15	16439677
STAT1 signaling is associated with acquired crossresistance to doxorubicin and radiation in myeloma cell lines.	2007 Jan 1	17072862
Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial.	2007 Jul 21	17658394
Targeting lipid metabolism by the lipoprotein lipase inhibitor orlistat results in apoptosis of B-cell chronic lymphocytic leukemia cells.	2008 Mar	18079738
Fatal acute liver failure due to reactivation of hepatitis B following treatment with fludarabine/cyclophosphamide/rituximab for low grade non-Hodgkin's lymphoma.	2008 Oct 27	19008178
Treosulfan/fludarabine as an allogeneic hematopoietic stem cell transplant conditioning regimen for high-risk patients.	2008 Sep	18626885
Fludarabine in the treatment of chronic lymphocytic leukemia: a review.	2009 Feb	19436622
Inhibitory effect of leptin on rosiglitazone-induced differentiation of primary adipocytes prepared from TallyHO/Jng mice.	2011 Mar 25	21352814

Patents

Sample Use Guides

In Vivo Use Guide

Chronic Lymphocytic Leukemia (CLL): The recommended adult dose is 25 mg/m2 administered intravenously over a period of approximately 30 minutes daily for five consecutive days. Each 5-day course of treatment should commence every 28 days.

Route of Administration: Intravenous

In Vitro Use Guide

The growth of RPMI8226 and KM3 cells was suppressed by fludarabine treatment in a dose and time-dependent manner. After treatment with fludarabine for 24 h, the IC(50) for RPMI8226 cells was 2.13 µg/ml, and 0.36 µg/ml for KM3 cells. Apoptotic cells of RPMI8226 and KM3 increased in a dose- dependent manner after exposure to fludarabine for 24 h. Western blot analysis showed the activation of caspase-3 and PARP in the MM cells treated with fludarabine.

Name

Type

Language

FLUDARABINE

Official Name

English

FLURADOSA

Brand Name

English

FLUDARABINE PHOSPHATE IMPURITY, 2-FLUORO-ARA-ADENINE- [USP IMPURITY]

Common Name

English

NSC-118218

Code

English

9-.BETA.-D-ARABINOFURANOSYL-2-FLUOROADENINE

Common Name

English

FLUDARABINE [HSDB]

Common Name

English

2-F-ARAA

Common Name

English

2-FLUORO-9-.BETA.-D-ARABINOFURANOSYLADENINE

Common Name

English

FLUDARABINE [VANDF]

Common Name

English

fludarabine [INN]

Common Name

English

Fludarabine [WHO-DD]

Common Name

English

2-FLUOROVIDARABINE

Common Name

English

FLUDARABINE [MI]

Common Name

English

9-.BETA.-D-ARABINOFURANOSYL-2-FLUORO-9H-PURIN-6-AMINE

Common Name

English

FLUDARABINE PHOSPHATE IMPURITY E [EP IMPURITY]

Common Name

English

2-FLUORO ARA-A

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2150