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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 of FAZARABINE

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
Molecular Formula C8H12N4O5
Molecular Weight 244.2047
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Interacts
323
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse 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

AEs

AESignificanceDosePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1650
 yes [IC50 11.7704 uM]
PubMed

PubMed

TitleDatePubMed
DNA methyltransferase inhibitors-state of the art.
2002 Nov
Patents

Patents

JP2011525180A
180

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).
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:16:48 UTC 2023
Edited
by admin
on Sat Dec 16 16:16:48 UTC 2023
Record UNII
5V71D8JOKK
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FAZARABINE
INN   MART.   USAN   WHO-DD  
USAN   INN  
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
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID401024360
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
CHEBI
141077
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
CAS
65886-71-7
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
NSC
281272
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
MESH
C022121
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
USAN
W-143
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
FDA UNII
5V71D8JOKK
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
INN
6022
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
NCI_THESAURUS
C1096
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
EVMPD
SUB07517MIG
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
ChEMBL
CHEMBL2106666
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
SMS_ID
100000081785
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
PUBCHEM
47751
Created by admin on Sat Dec 16 16:16:48 UTC 2023 , Edited by admin on Sat Dec 16 16:16:48 UTC 2023
PRIMARY
Related Record Type Details
Structure of FAZARABINE
ACTIVE MOIETY
NIH
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