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 282 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 609 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 1147	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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1379523	DLT: Granulocytopenia... Dose limiting toxicities: Granulocytopenia (80%) Sources: https://pubmed.ncbi.nlm.nih.gov/1379523
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10492074	Other AEs: Neurotoxicity, Fluid overload... Other AEs: Neurotoxicity (grade 3, 66.7%) Fluid overload (100%) Sources: https://pubmed.ncbi.nlm.nih.gov/10492074

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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/1379523
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10492074
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	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10492074

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006318	yes [IC50 11.7704 uM]

PubMed

Title	Date	PubMed
DNA methyltransferase inhibitors-state of the art.	2002-11	12419742

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

NSC-281272

Preferred Name

English

5-AZACYTOSINE ARABINOSIDE

Common Name

English

Fazarabine [WHO-DD]

Common Name

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