U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H43N3O6
Molecular Weight 481.6254
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CYTARABINE-5'-PALMITATE

SMILES

CCCCCCCCCCCCCCCC(=O)OC[C@H]1O[C@H]([C@@H](O)[C@@H]1O)N2C=CC(N)=NC2=O

InChI

InChIKey=SHBAKEKBTCPUFI-OUJCMCIWSA-N
InChI=1S/C25H43N3O6/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-21(29)33-18-19-22(30)23(31)24(34-19)28-17-16-20(26)27-25(28)32/h16-17,19,22-24,30-31H,2-15,18H2,1H3,(H2,26,27,32)/t19-,22-,23+,24-/m1/s1

HIDE SMILES / InChI

Molecular Formula C25H43N3O6
Molecular Weight 481.6254
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Sources: www.accessdata.fda.gov/drugsatfda_docs/label/2011/021041s023lbl.pdf
Curator's Comment: Description was created using several sources including: http://www.ebi.ac.uk/chebi/searchId.do?chebiId=28680 http://www.tandfonline.com/doi/abs/10.1517/17425247.2010.527330

Cytarabine is a pyrimidine nucleoside analog. Cytarabine or cytosine arabinoside (Cytosar-U or Depocyt) is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia (AML) and non-Hodgkin lymphoma. It also has antiviral and immunosuppressant properties. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. It is a cell cycle phase-specific, affecting cells only during the S phase of cell division. Intracellularly, cytarabine is converted into cytarabine-5-triphosphate (ara-CTP), which is the active metabolite. The mechanism of action is not completely understood, but it appears that ara-CTP acts primarily through inhibition of DNA polymerase. Incorporation into DNA and RNA may also contribute to cytarabine cytotoxicity. Cytarabine is cytotoxic to a wide variety of proliferating mammalian cells in culture.The drug has a short plasma half-life, low stability and limited bioavailability. Overdosing of patients with continuous infusions may lead to side effects. Thus, various prodrug strategies and delivery systems have been explored extensively to enhance the half-life, stability and delivery of cytarabine. Alternative, delivery systems of cytarabine have emerged for the treatment of different cancers. The liposomal-cytarabine formulation has been approved for the treatment of lymphomatous meningitis.

CNS Activity

Originator

Curator's Comment: Cytarabine was first synthesized in 1959 by Richard Walwick, Walden Roberts, and Charles Dekker at the University of California, Berkeley. It was approved by the United States Food and Drug Administration in June 1969, and was initially marketed in the U.S. by Upjohn under the trade name Cytosar-U and is at present manufactured by Pfizer, Sicor Pharmaceuticals and Teva. CYTOSAR (cytarabine injection) was developed in September 1994 Dana-­Farber Cancer Institute and is manufactured by Pfizer and Perrigo. DEPOCYT - (cytarabine injection, lipid complex) manufactured by Manufactured by: Pacira Pharmaceuticals Inc., distributed by Sigma-Tau Pharmaceutical, Inc. is an intrathecal cancer chemotherapeutic agent approved by FDA is used for the treatment of lymphomatous meningitis.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Sources: www.accessdata.fda.gov/drugsatfda_docs/label/2011/021041s023lbl.pdf
Primary
CYTARABINE

Approved Use

Cytarabine in combination with other approved anticancer drugs is indicated for remission induction in acute non-lymphocytic leukemia of adults and children. It has also been found useful in the treatment of acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia. Intrathecal administration of cytarabine injection (preservative-free only) is indicated for the prophylaxis and treatment of meningeal leukemia.

Launch Date

1969
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
62.2 μg/mL
100 mg/m² 1 times / day multiple, intravenous
dose: 100 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: DAUNORUBICIN
CYTARABINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1900 μg × h/mL
100 mg/m² 1 times / day multiple, intravenous
dose: 100 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: DAUNORUBICIN
CYTARABINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
40.4 h
100 mg/m² 1 times / day multiple, intravenous
dose: 100 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered: DAUNORUBICIN
CYTARABINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
80 h
50 mg single, intrathecal
dose: 50 mg
route of administration: Intrathecal
experiment type: SINGLE
co-administered:
CYTARABINE unknown
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
4.5 g/m2 2 times / day multiple, intravenous
Highest studied dose
Dose: 4.5 g/m2, 2 times / day
Route: intravenous
Route: multiple
Dose: 4.5 g/m2, 2 times / day
Sources: Page: p.363, 366
unhealthy, 16-76
n = 6
Health Status: unhealthy
Condition: Acute leukemia
Age Group: 16-76
Sex: M+F
Population Size: 6
Sources: Page: p.363, 366
Disc. AE: Cerebellar disorder NOS, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Cerebellar disorder NOS (grade 4, 66.7%)
Diarrhea (grade 3, 66.7%)
Sources: Page: p.363, 366
4.5 g/m2 2 times / day multiple, intravenous
Highest studied dose
Dose: 4.5 g/m2, 2 times / day
Route: intravenous
Route: multiple
Dose: 4.5 g/m2, 2 times / day
Sources: Page: p.2578
unhealthy, 16-76
n = 6
Health Status: unhealthy
Condition: Acute leukemia
Age Group: 16-76
Sex: M+F
Population Size: 6
Sources: Page: p.2578
Disc. AE: Cerebellar disorder NOS, Cerebellar disorder NOS...
AEs leading to
discontinuation/dose reduction:
Cerebellar disorder NOS (grade 4, 33.3%)
Cerebellar disorder NOS (grade 5, 16.7%)
Sources: Page: p.2578
3 g/m2 2 times / day multiple, intravenous
MTD
Dose: 3 g/m2, 2 times / day
Route: intravenous
Route: multiple
Dose: 3 g/m2, 2 times / day
Sources: Page: p.366
unhealthy, 16-76
n = 27
Health Status: unhealthy
Condition: Acute leukemia
Age Group: 16-76
Sex: M+F
Population Size: 27
Sources: Page: p.366
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Disc. AE: Bone marrow depression, Leukopenia...
AEs leading to
discontinuation/dose reduction:
Bone marrow depression
Leukopenia
Thrombocytopenia
Anemia
Nausea
Vomiting
Diarrhea
Abdominal pain
Oral ulceration
Hepatic dysfunction NOS
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Diarrhea grade 3, 66.7%
Disc. AE
4.5 g/m2 2 times / day multiple, intravenous
Highest studied dose
Dose: 4.5 g/m2, 2 times / day
Route: intravenous
Route: multiple
Dose: 4.5 g/m2, 2 times / day
Sources: Page: p.363, 366
unhealthy, 16-76
n = 6
Health Status: unhealthy
Condition: Acute leukemia
Age Group: 16-76
Sex: M+F
Population Size: 6
Sources: Page: p.363, 366
Cerebellar disorder NOS grade 4, 66.7%
Disc. AE
4.5 g/m2 2 times / day multiple, intravenous
Highest studied dose
Dose: 4.5 g/m2, 2 times / day
Route: intravenous
Route: multiple
Dose: 4.5 g/m2, 2 times / day
Sources: Page: p.363, 366
unhealthy, 16-76
n = 6
Health Status: unhealthy
Condition: Acute leukemia
Age Group: 16-76
Sex: M+F
Population Size: 6
Sources: Page: p.363, 366
Cerebellar disorder NOS grade 4, 33.3%
Disc. AE
4.5 g/m2 2 times / day multiple, intravenous
Highest studied dose
Dose: 4.5 g/m2, 2 times / day
Route: intravenous
Route: multiple
Dose: 4.5 g/m2, 2 times / day
Sources: Page: p.2578
unhealthy, 16-76
n = 6
Health Status: unhealthy
Condition: Acute leukemia
Age Group: 16-76
Sex: M+F
Population Size: 6
Sources: Page: p.2578
Cerebellar disorder NOS grade 5, 16.7%
Disc. AE
4.5 g/m2 2 times / day multiple, intravenous
Highest studied dose
Dose: 4.5 g/m2, 2 times / day
Route: intravenous
Route: multiple
Dose: 4.5 g/m2, 2 times / day
Sources: Page: p.2578
unhealthy, 16-76
n = 6
Health Status: unhealthy
Condition: Acute leukemia
Age Group: 16-76
Sex: M+F
Population Size: 6
Sources: Page: p.2578
Abdominal pain Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Anemia Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Bone marrow depression Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Diarrhea Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Hepatic dysfunction NOS Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Leukopenia Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Nausea Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Oral ulceration Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Thrombocytopenia Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Vomiting Disc. AE
100 mg/m2 1 times / day multiple, intravenous
Recommended
Dose: 100 mg/m2, 1 times / day
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Acute non-lymphocytic leukemia
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 6.6 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
Lenograstim and filgrastim effects on neutrophil motility in patients undergoing chemotherapy: evaluation by computer-assisted image analysis.
2001 Apr
Primary high-grade mucosa-associated lymphoid tissue-type lymphoma of the cervix presenting as a common endocervical polyp.
2001 Apr
2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine: a novel anticancer nucleoside analog that causes both DNA strand breaks and G(2) arrest.
2001 Apr
Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute leukemia after allogeneic bone marrow transplantation.
2001 Apr
Cell cycle-related changes in regulatory volume decrease and volume-sensitive chloride conductance in mouse fibroblasts.
2001 Apr
The neuron-glia signal beta-neuregulin promotes Schwann cell motility via the MAPK pathway.
2001 Apr 1
Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased-risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: results of the European Organization for Research and Treatment of Cancer 58881 randomized phase III trial.
2001 Apr 1
In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents.
2001 Apr 1
Respiratory chain-generated oxidative stress following treatment of leukemic blasts with DNA-damaging agents.
2001 Apr 1
The combination of chemotherapy and systemic immunotherapy with soluble B7-immunoglobulin G leads to cure of murine leukemia and lymphoma and demonstration of tumor-specific memory responses.
2001 Apr 15
Involvement of oxygen radicals in cytarabine-induced apoptosis in human polymorphonuclear cells.
2001 Apr 15
Parotid mucoepidermoid carcinoma following chemotherapy for childhood acute lymphoblastic leukemia.
2001 Apr-May
Prognostic value of day 14 blast percentage and the absolute blast index in bone marrow of children with acute lymphoblastic leukemia.
2001 Apr-May
[Philadelphia chromosome-positive acute lymphoblastic leukemia with monosomy 7 successfully treated with intermediate- and high-dose ara-C].
2001 Feb
Induction therapy of adult acute lymphocytic leukemia without the use of vincristine or prednisone.
2001 Feb
Chemotherapy for acute myelogenous leukemia in the elderly with cytarabine, mitoxantrone, and granulocyte-macrophage colony-stimulating factor.
2001 Feb
Temporary response of localized intracranial mast cell sarcoma to combination chemotherapy.
2001 Feb
Primary central nervous system lymphoma in childhood presenting as progressive panhypopituitarism.
2001 Feb
Bilateral breast relapse in acute myelogenous leukemia.
2001 Feb
Bone marrow involvement by nasal NK cell lymphoma at diagnosis is uncommon.
2001 Feb
[Is it useful to perform a (67)gallium scintigraphy in the follow-up of patients with gastric lymphoma?].
2001 Feb
Mutations in ras proto-oncogenes are associated with lower mdr1 gene expression in adult acute myeloid leukaemia.
2001 Feb
Transfusion of peripheral blood stem cells from donor homozygous for a shared HLA-haplotype: avoiding fatal transfusion-associated graft-versus-host disease while preserving anti-leukemic effect.
2001 Feb 15
Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study.
2001 Feb 15
Topoisomerase II inhibitor induced leukemia in a patient with AIDS.
2001 Feb 16
[Palpable mantel cell lymphoma in the breast].
2001 Feb 3
Allogeneic bone marrow transplantation in children failing prior autologous bone marrow transplantation.
2001 Jan
The biology and treatment of chronic myelogenous leukemia.
2001 Jan
Cyclosporin increases cellular idarubicin and idarubicinol concentrations in relapsed or refractory AML mainly due to reduced systemic clearance.
2001 Jan
[Outcome of acute myelogenous leukemia in 41 patients treated with idarubicin: the prognosis of t(8;21) cases].
2001 Jan
Aseptic meningitis in a child after systemic treatment with high dose cytarabine.
2001 Jan
Induction of differentiation of acute promyelocytic leukemia cells by a cytidine deaminase-resistant analogue of 1-beta-D-arabinofuranosylcytosine, 1-(2-deoxy-2-methylene-beta-D-erythro-pentofuranosyl)cytidine.
2001 Jan 1
Simultaneous treatment with 1-beta-D-arabinofuranosylcytosine and daunorubicin induces cross-resistance to both drugs due to a combination-specific mechanism in HL60 cells.
2001 Jan 1
The CAG regimen (low-dose cytarabine, aclarubicin hydrochloride and granulocyte colony-stimulating factor) for the treatment of elderly acute myelomonocytic leukaemia: a case study.
2001 Jan-Feb
Results of IDA-FLAG programme in the treatment of recurrent acute myeloblastic leukaemia--preliminary report.
2001 Jan-Feb
Toxic epidermal necrolysis after the use of high-dose cytosine arabinoside.
2001 Jan-Feb
Therapy of acute myeloid leukemia.
2001 Jan-Feb
Outcome of relapsed or refractory childhood B-cell acute lymphoblastic leukaemia and B-cell non-Hodgkin's lymphoma treated with the UKCCSG 9003/9002 protocols.
2001 Mar
Neutrophilic eccrine hidradenitis in two neutropaenic patients.
2001 Mar
[All-trans retinoic acid combined with low-dose cytosine arabinoside treatment for acute myelogenous leukemia with trilineage myelodysplasia--a case report].
2001 Mar
Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials.
2001 Mar
Cytogenetic subgroups in acute myeloid leukemia differ in proliferative activity and response to GM-CSF.
2001 Mar
Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93. AML-BFM Study Group.
2001 Mar
Synergistic activity of the new ABL-specific tyrosine kinase inhibitor STI571 and chemotherapeutic drugs on BCR-ABL-positive chronic myelogenous leukemia cells.
2001 Mar
Combination chemotherapy utilizing continuous infusion of intermediate-dose cytarabine for refractory or recurrent acute myeloid leukemia.
2001 Mar
Isodicentric 7p, idic(7)(q11.2), in acute myeloid leukemia associated with older age and favorable response to induction chemotherapy: a new clinical entity?
2001 Mar
Severe hepatic injury associated with lipid formulations of amphotericin B.
2001 Mar 1
Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia.
2001 Mar 15
Total body irradiation before allogeneic bone marrow transplantation: is more dose better?
2001 Mar 15
Circumvention of ara-C resistance by aphidicolin in blast cells from patients with AML.
2001 Mar 2
Patents

Sample Use Guides

Induction therapy: DepoCyt (cytarabine liposome injection), 50 mg, administered intrathecally (intraventricular or lumbar puncture) every 14 days for 2 doses (weeks 1 and 3). Consolidation therapy: DepoCyt, 50 mg, administered intrathecally (intraventricular or lumbar puncture) every 14 days for 3 doses (weeks 5, 7 and 9) followed by 1 additional dose at week 13. Maintenance: DepoCyt, 50 mg, administered intrathecally (intraventricular or lumbar puncture) every 28 days for 4 doses (weeks 17, 21, 25 and 29).
Route of Administration: Intratracheal
In Vitro Use Guide
Curator's Comment: The effect of Ara-C (0.1 μM) treatment on HUVEC proliferation alone or in drug combinations compared to drug-free control cultures. Results are expressed as mean percentage ± SEM from three independent experiments (six replicates per condition) relative to corresponding untreated control cultures.
Human umbilical vein endothelial cells (HUVECs) and human osteosarcoma cell line (Cal72) were incubated with various concentrations of Cytarabine (Ara-C) (0.01–20 μM) for 3 days
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:23:28 GMT 2023
Edited
by admin
on Fri Dec 15 15:23:28 GMT 2023
Record UNII
TFX122G3KD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CYTARABINE-5'-PALMITATE
Common Name English
CYTOSINE, 1-.BETA.-D-ARABINOFURANOSYL-, 5'-PALMITATE
Systematic Name English
ARACYTIDINE 5'-PALMITATE
Common Name English
P-ARA-C
Common Name English
PALMITOYL CYTARABINE
Common Name English
ARABINOSYL CYTOSINE PALMITATE
Common Name English
NSC-135962
Code English
Code System Code Type Description
NSC
135962
Created by admin on Fri Dec 15 15:23:28 GMT 2023 , Edited by admin on Fri Dec 15 15:23:28 GMT 2023
PRIMARY
CAS
31088-06-9
Created by admin on Fri Dec 15 15:23:28 GMT 2023 , Edited by admin on Fri Dec 15 15:23:28 GMT 2023
PRIMARY
PUBCHEM
35731
Created by admin on Fri Dec 15 15:23:28 GMT 2023 , Edited by admin on Fri Dec 15 15:23:28 GMT 2023
PRIMARY
EPA CompTox
DTXSID70953190
Created by admin on Fri Dec 15 15:23:28 GMT 2023 , Edited by admin on Fri Dec 15 15:23:28 GMT 2023
PRIMARY
FDA UNII
TFX122G3KD
Created by admin on Fri Dec 15 15:23:28 GMT 2023 , Edited by admin on Fri Dec 15 15:23:28 GMT 2023
PRIMARY
Related Record Type Details
ACTIVE MOIETY