Clofarabine

Names

[ Name ]:
Clofarabine

[Synonym ]:
Clofarex
(2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
(2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxyméthyl)tétrahydrofuran-3-ol
9H-Purin-6-amine, 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-
2-Chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine
(2R,3R,4S,5R)-5-(6-Amino-2-chlor-9H-purin-9-yl)-4-fluor-2-(hydroxymethyl)tetrahydrofuran-3-ol
(2R,3R,4S,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol
2-chloro-2'-arabino-fluoro-2'-deoxyadenosine
Cl-F-Ara-A
Clofarabine
Clofarabine [USAN]
Clolar
2-Chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine
MFCD00871077

Biological Activity

[Description]:

Clofarabine(Clolar; Clofarex) inhibits the enzymatic activities of ribonucleotide reductase (IC50 = 65 nM) and DNA polymerase.IC50 Value: 65 nMTarget: in vitro: Clofarabine is a second generation purine nucleoside analog with antineoplastic activity. It is phosphorylated intracellularly, which inhibits the enzymatic activities of ribonucleotide reductase (IC50 = 65 nM) and DNA polymerase, resulting in inhibition of DNA repair and synthesis of DNA and RNA. This nucleoside analog also disrupts mitochondrial function and membrane integrity, resulting in the release of pre-apoptotic factors, including cytochrome C and apoptotic-inducing factor, which activate apoptosis.in vivo: Clofarabine is used for treating relapsed or refractory acute lymphoblastic leukaemia (ALL) in children, after at least two other types of treatment have failed.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> Nucleoside Antimetabolite/Analog

Research Areas >> Cancer

Research Areas >> Metabolic Disease

[References]

[1]. Bonate et al Discovery and development of clofarabine: a nucleoside analogue for treating cancer. Nat.Rev.Drug Discov. (2006)5 855.

[2]. Ghanem H, Kantarjian H, Ohanian M, Jabbour E.The Role of Clofarabine in Acute Myeloid Leukemia.Leuk Lymphoma. 2012 Sep 7.

[3]. Abd Elmoneim A, Gore L, Ricklis RM, Boklan J, Cooper T, Narendran A, Rolla K, Scott T, Arceci RJ.Phase I dose-escalation trial of clofarabine followed by escalating doses of fractionated cyclophosphamide in children with relapsed or refractory acute leukemias.Pediatr Blood Cancer. 2012 Aug 8. doi: 10.1002/pbc.24264.

[4]. Thudium KE, Ghoshal S, Fetterly GJ, Haese JP, Karpf AR, Wetzler M.Synergism between clofarabine and decitabine through p53R2: A pharmacodynamic drug-drug interaction modeling.Leuk Res. 2012 Aug 9.

[5]. Aye Y, Brignole EJ, Long MJ, Chittuluru J, Drennan CL, Asturias FJ, Stubbe J.Clofarabine Targets the Large Subunit (α) of Human Ribonucleotide Reductase in Live Cells by Assembly into Persistent Hexamers.Chem Biol. 2012 Jul 27;19(7):799-805.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
2.1±0.1 g/cm3

[ Boiling Point ]:
599.5±60.0 °C at 760 mmHg

[ Melting Point ]:
228-2310C

[ Molecular Formula ]:
C₁₀H₁₁ClFN₅O₃

[ Molecular Weight ]:
303.677

[ Flash Point ]:
316.4±32.9 °C

[ Exact Mass ]:
303.053436

[ PSA ]:
119.31000

[ LogP ]:
0.24

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.844

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UD7473000

CHEMICAL NAME :: 9H-Purin-6-amine, 2-chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) -

CAS REGISTRY NUMBER :: 123318-82-1

LAST UPDATED :: 199706

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C10-H11-Cl-F-N5-O3

MOLECULAR WEIGHT :: 303.71

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Human Leukocyte

DOSE/DURATION :: 50 nmol/L

REFERENCE :: CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941- Volume(issue)/page/year: 51,2386,1991

Safety Information

[ Symbol ]:

GHS06

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H300

[ Precautionary Statements ]:
P264-P301 + P310

[ Personal Protective Equipment ]:
Eyeshields;Faceshields;Gloves;type P2 (EN 143) respirator cartridges

[ Hazard Codes ]:
Xi,C

[ Risk Phrases ]:
R36/37/38:Irritating to eyes, respiratory system and skin . R20/21/22:Harmful by inhalation, in contact with skin and if swallowed .

[ Safety Phrases ]:
S26-S36-S45-S36/37/39

[ RIDADR ]:
UN 2735 8/PG 3

[ WGK Germany ]:
3

[ RTECS ]:
DP5550000

[ Packaging Group ]:
III

[ Hazard Class ]:
8

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

The potential of clofarabine in MLL-rearranged infant acute lymphoblastic leukaemia.

Eur. J. Cancer 51 , 2008-21, (2015)

MLL-rearranged acute lymphoblastic leukaemia (ALL) in infants is the most difficult-to-treat type of childhood ALL, displaying a chemotherapy-resistant phenotype, and unique histone modifications, gen...

Preclinical examination of clofarabine in pediatric ependymoma: intratumoral concentrations insufficient to warrant further study.

Cancer Chemother. Pharmacol. 75 , 897-906, (2015)

Clofarabine, a deoxyadenosine analog, was an active anticancer drug in our in vitro high-throughput screening against mouse ependymoma neurospheres. To characterize the clofarabine disposition in mice...

Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells.

J. Korean Med. Sci. 29(11) , 1464-72, (2014)

Mcl-1 and Bcl-xL, key anti-apoptotic proteins of the Bcl-2 family, have attracted attention as important molecules in the cell survival and drug resistance. In this study, we investigated whether inhi...