FAZARABINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H12N4O5
Molecular Weight	244.2047
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=NC(=O)N(C=N1)[C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O

InChI

InChIKey=NMUSYJAQQFHJEW-ARQDHWQXSA-N

InChI=1S/C8H12N4O5/c9-7-10-2-12(8(16)11-7)6-5(15)4(14)3(1-13)17-6/h2-6,13-15H,1H2,(H2,9,11,16)/t3-,4-,5+,6-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2449402 | https://www.ncbi.nlm.nih.gov/pubmed/7688714

Fazarabine (Arabinofuranosyl-5-azacytosine) is a synthetic pyrimidine nucleoside which combines the arabinose sugar of cytosine arabinoside with the triazine base of 5-azacytidine. It has demonstrated activity against a variety of human solid tumor xenografts including colon, lung and breast cancers. It has been selected by the Division of Cancer Treatment, National Cancer Institute for clinical development as an antineoplastic agent based on its high degree of activity against a broad range of tumor types in preclinical studies. Therapeutic activity has been observed against murine and human leukemias, transplantable murine solid tumors, and human tumor xenografts. Arabinosyl-5-azacytosine exhibited a broader spectrum of activity against human solid tumors than cytosine arabinoside. The mode of action of fazarabine is mediated through its incorporation into DNA and inhibition of DNA synthesis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278 Target ID: CHEMBL2311221 Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=40564 \| https://www.ncbi.nlm.nih.gov/pubmed/1713459 \| https://www.ncbi.nlm.nih.gov/pubmed/2410096	Interacts 323

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1376723 https://www.ncbi.nlm.nih.gov/pubmed/2475244 https://www.ncbi.nlm.nih.gov/pubmed/9815635	Primary		Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
2 mg/m2/hour 1 times / hour multiple, intravenous MTD Dose: 2 mg/m2/hour, 1 times / hour Route: intravenous Route: multiple Dose: 2 mg/m2/hour, 1 times / hour Sources: https://pubmed.ncbi.nlm.nih.gov/1379523 Page: p.323	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/1379523 Page: p.323	DLT: Granulocytopenia... Dose limiting toxicities: Granulocytopenia (80%) Sources: https://pubmed.ncbi.nlm.nih.gov/1379523 Page: p.323
425 mg/m2/hour 1 times / hour multiple, intravenous MTD Dose: 425 mg/m2/hour, 1 times / hour Route: intravenous Route: multiple Dose: 425 mg/m2/hour, 1 times / hour Sources: https://pubmed.ncbi.nlm.nih.gov/10492074 Page: p.514	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/10492074 Page: p.514	Other AEs: Neurotoxicity, Fluid overload... Other AEs: Neurotoxicity (grade 3, 66.7%) Fluid overload (100%) Sources: https://pubmed.ncbi.nlm.nih.gov/10492074 Page: p.514

AEs

AE	Significance	Dose	Population
Granulocytopenia	80% DLT	2 mg/m2/hour 1 times / hour multiple, intravenous MTD Dose: 2 mg/m2/hour, 1 times / hour Route: intravenous Route: multiple Dose: 2 mg/m2/hour, 1 times / hour Sources: https://pubmed.ncbi.nlm.nih.gov/1379523 Page: p.323	unhealthy, ADULT n = 5 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/1379523 Page: p.323
Fluid overload	100%	425 mg/m2/hour 1 times / hour multiple, intravenous MTD Dose: 425 mg/m2/hour, 1 times / hour Route: intravenous Route: multiple Dose: 425 mg/m2/hour, 1 times / hour Sources: https://pubmed.ncbi.nlm.nih.gov/10492074 Page: p.514	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/10492074 Page: p.514
Neurotoxicity	grade 3, 66.7%	425 mg/m2/hour 1 times / hour multiple, intravenous MTD Dose: 425 mg/m2/hour, 1 times / hour Route: intravenous Route: multiple Dose: 425 mg/m2/hour, 1 times / hour Sources: https://pubmed.ncbi.nlm.nih.gov/10492074 Page: p.514	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: leukemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/10492074 Page: p.514

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006318	yes [IC50 11.7704 uM]

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

Fourteen consecutive female patients with metastatic breast cancer received a total of 31 courses of fazarabine at a dose of 2 mg/m2/hour x 72 hours (48 mg/m2/day x 3) as a continuous infusion.

Route of Administration: Intravenous

In Vitro Use Guide

In vitro clonogenic assays with L1210 exposed to Fazarabine (Ara-AC) indicated that cytotoxic concentrations of 1 to 10 ug/ml were optimal at exposure times of 72 hours or longer (3 to 4 logs of L1210 cell kill).

Name

Type

Language

FAZARABINE

Official Name

English

5-AZACYTOSINE ARABINOSIDE

Common Name

English

Fazarabine [WHO-DD]

Common Name

English

NSC-281272

Code

English

KYMARABINE

Common Name

English

FAZARABINE [USAN]

Common Name

English

FAZARABINE [MART.]

Common Name

English

ARA-AC

Common Name

English

fazarabine [INN]

Common Name

English

1,3,5-TRIAZIN-2(1H)-ONE, 4-AMINO-1-.BETA.-D-ARABINOFURANOSYL-

Common Name

English

4-AMINO-1-.BETA.-D-ARABINOFURANOSYL-1,3,5-TRIAZIN-2(1H)-ONE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1557