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MedKoo Cat#: 100180 | Name: Clofarabine
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Clofarabine is a second generation purine nucleoside analog with antineoplastic activity. Clofarabine is phosphorylated intracellularly to the cytotoxic active 5'-triphosphate metabolite, which inhibits the enzymatic activities of ribonucleotide reductase 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.

Chemical Structure

Clofarabine
Clofarabine
CAS#123318-82-1

Theoretical Analysis

MedKoo Cat#: 100180

Name: Clofarabine

CAS#: 123318-82-1

Chemical Formula: C10H11ClFN5O3

Exact Mass: 303.0535

Molecular Weight: 303.68

Elemental Analysis: C, 39.55; H, 3.65; Cl, 11.67; F, 6.26; N, 23.06; O, 15.81

Price and Availability

Size Price Availability Quantity
100mg USD 450.00 2 Weeks
250mg USD 850.00 2 Weeks
500mg USD 1,250.00 2 Weeks
1g USD 1,850.00 2 Weeks
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Synonym
C1-F-Ara-A; Clofarabine, US brand names: Clofarex; Clolar. Abbreviation: CAFdA;
IUPAC/Chemical Name
(2S,3S,4R,5R)-5-(6-amino-2-chloro-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol
InChi Key
WDDPHFBMKLOVOX-IETYGKGOSA-N
InChi Code
InChI=1S/C10H11ClFN5O3/c11-10-15-7(13)5-8(16-10)17(2-14-5)9-4(12)6(19)3(1-18)20-9/h2-4,6,9,18-19H,1H2,(H2,13,15,16)/t3-,4+,6-,9+/m0/s1
SMILES Code
O[C@H]1[C@H](CO)O[C@@H](N2C=NC3=C(N)N=C(Cl)N=C23)[C@@H]1F
Appearance
Solid powder
Purity
>97% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Clolar® (clofarabine) injection contains clofarabine, a purine nucleosideanti-metabolite. Clolar® (1 mg/mL) is supplied in a 20 mL, single-use vial. The 20 mL vial contains 20 mg clofarabine formulated in 20 mL unbuffered normal saline (comprised of Water for Injection, USP, and Sodium Chloride, USP). The pH range of the solution is 4.5 to 7.5. The solution is sterile, clear and practically colorless, and free from foreign matter. The chemical structure of clofarabine is 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine. The molecular formula of clofarabine is C10H11ClFN5O3 with a molecular weight of 303.68.   Clofarabine is a purine nucleoside antimetabolite marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. It is FDA-approved for treating a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL) in children, after at least two other types of treatment have failed. It is not known if it extends life expectancy. Some investigations of effectiveness in cases of acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) have been carried out. Ongoing trials are assessing its efficacy, if any, for managing other cancers. see http://en.wikipedia.org/wiki/Clofarabine.   Mechanism of Action Clofarabine is sequentially metabolized intracellu-larly to the 5'-monophosphate metabolite by deoxycytidine kinase and mono- and di-phospho-kinases to the active 5'-triphosphate metabolite. Clofarabine has high affinity for the activating phosphorylating enzyme, deoxycytidine kinase, equal to or greater than that of the natural substrate, deoxycytidine. Clofarabine inhibits DNA synthesis by decreasing cellular deoxynucleotide triphosphate pools through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through incorporation into the DNA chain by competitive inhibition of DNA polymerases. The affinity of clofarabine triphosphate for these enzymes is similar to or greater than that of deoxyadenosine triphosphate. In preclinical models, clofarabine has demonstrated the ability to inhibit DNA repair by incorporation into the DNA chain during the repair process. Clofarabine 5'-triphosphate also disrupts the integrity of mitochondrial membrane, leading to the release of the pro-apoptotic mitochondrial proteins, cytochrome C and apoptosis-inducing factor, leading to programmed cell death. Clofarabine is cytotoxic to rapidly proliferating and quiescent cancer cell types in vitro.    
Biological target:
Clofarabine(Clolar; Clofarex) inhibits the enzymatic activities of ribonucleotide reductase (IC50 = 65 nM) and DNA polymerase.
In vitro activity:
This study consistently observed increased phosphorylation of ERK1/2, MSK1/2, and CREB after clofarabine treatment (Fig 3A). Reference: PLoS One. 2021; 16(6): e0253170. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208565/
In vivo activity:
Both drugs drastically inhibited anchorage-independent growth of ES cells, but clofarabine was more effective in inhibiting growth of three different ES mouse xenografts. Reference: Oncogene. 2018 Apr;37(16):2181-2196. https://pubmed.ncbi.nlm.nih.gov/29382926/
Solvent mg/mL mM
Solubility
DMSO 40.1 132.01
DMSO:PBS (pH 7.2) (1:1) 0.5 1.65
DMF 20.0 65.86
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 303.68 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Sevim H, Çelik H, Düşünceli L, Ceyhan CS, Molotkova A, Nakazawa K, Graham GT, Petro JR, Toretsky JA, Üren A. Clofarabine induces ERK/MSK/CREB activation through inhibiting CD99 on Ewing sarcoma cells. PLoS One. 2021 Jun 16;16(6):e0253170. doi: 10.1371/journal.pone.0253170. PMID: 34133426; PMCID: PMC8208565. 2. Çelik H, Sciandra M, Flashner B, Gelmez E, Kayraklıoğlu N, Allegakoen DV, Petro JR, Conn EJ, Hour S, Han J, Oktay L, Tiwari PB, Hayran M, Harris BT, Manara MC, Toretsky JA, Scotlandi K, Üren A. Clofarabine inhibits Ewing sarcoma growth through a novel molecular mechanism involving direct binding to CD99. Oncogene. 2018 Apr;37(16):2181-2196. doi: 10.1038/s41388-017-0080-4. Epub 2018 Jan 31. PMID: 29382926.
In vitro protocol:
1. Sevim H, Çelik H, Düşünceli L, Ceyhan CS, Molotkova A, Nakazawa K, Graham GT, Petro JR, Toretsky JA, Üren A. Clofarabine induces ERK/MSK/CREB activation through inhibiting CD99 on Ewing sarcoma cells. PLoS One. 2021 Jun 16;16(6):e0253170. doi: 10.1371/journal.pone.0253170. PMID: 34133426; PMCID: PMC8208565.
In vivo protocol:
1. Çelik H, Sciandra M, Flashner B, Gelmez E, Kayraklıoğlu N, Allegakoen DV, Petro JR, Conn EJ, Hour S, Han J, Oktay L, Tiwari PB, Hayran M, Harris BT, Manara MC, Toretsky JA, Scotlandi K, Üren A. Clofarabine inhibits Ewing sarcoma growth through a novel molecular mechanism involving direct binding to CD99. Oncogene. 2018 Apr;37(16):2181-2196. doi: 10.1038/s41388-017-0080-4. Epub 2018 Jan 31. PMID: 29382926.
1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Clofarabine. 2017 Oct 17. PMID: 31643513. 2: Pui CH, Jeha S. Clofarabine. Nat Rev Drug Discov. 2005 May;Suppl:S12-3. doi: 10.1038/nrd1724. PMID: 15962525. 3: Ghanem H, Jabbour E, Faderl S, Ghandhi V, Plunkett W, Kantarjian H. Clofarabine in leukemia. Expert Rev Hematol. 2010 Feb;3(1):15-22. doi: 10.1586/ehm.09.70. PMID: 21082931. 4: Clofarabine. Drugs R D. 2004;5(4):213-7. doi: 10.2165/00126839-200405040-00005. PMID: 15230627. 5: Tiu RV, Traina F, Sekeres MA. Clofarabine for myelodysplastic syndromes. Expert Opin Investig Drugs. 2011 Jul;20(7):1005-14. doi: 10.1517/13543784.2011.585967. Epub 2011 May 19. PMID: 21591997. 6: Pui CH, Jeha S, Kirkpatrick P. Clofarabine. Nat Rev Drug Discov. 2005 May;4(5):369-70. doi: 10.1038/nrd1724. PMID: 15902772. 7: Tran H, Yang D. Clofarabine in the treatment of newly diagnosed acute myeloid leukemia in older adults. Ann Pharmacother. 2012 Jan;46(1):89-96. doi: 10.1345/aph.1Q295. Epub 2011 Dec 13. PMID: 22170975. 8: Majda K, Lubecka K, Kaufman-Szymczyk A, Fabianowska-Majewska K. Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine)--biochemical aspects of anticancer activity. Acta Pol Pharm. 2011 Jul-Aug;68(4):459-66. PMID: 21796927. 9: Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S. Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30. doi: 10.1080/10428190701545644. PMID: 17852710. 10: Bryan J, Kantarjian H, Prescott H, Jabbour E. Clofarabine in the treatment of myelodysplastic syndromes. Expert Opin Investig Drugs. 2014 Feb;23(2):255-63. doi: 10.1517/13543784.2014.877887. PMID: 24410313. 11: Hijiya N, Barry E, Arceci RJ. Clofarabine in pediatric acute leukemia: current findings and issues. Pediatr Blood Cancer. 2012 Sep;59(3):417-22. doi: 10.1002/pbc.24112. Epub 2012 Feb 21. PMID: 22354543. 12: Musto P, Ferrara F. Clofarabine: in search of combinations for the treatment of patients with high-risk acute myeloid leukemia. Cancer. 2008 Oct 15;113(8):1995-8. doi: 10.1002/cncr.23804. PMID: 18780321. 13: Kline JP, Larson RA. Clofarabine in the treatment of acute myeloid leukaemia and acute lymphoblastic leukaemia: a review. Expert Opin Pharmacother. 2005 Dec;6(15):2711-8. doi: 10.1517/14656566.6.15.2711. PMID: 16316309. 14: Thomas X, Raffoux E, Elhamri M, Lobe I, Cannas G, Dombret H. Clofarabine for the treatment of adult acute myeloid leukemia. Future Oncol. 2009 Oct;5(8):1197-210. doi: 10.2217/fon.09.105. PMID: 19852733. 15: Gandhi V, Plunkett W. Clofarabine and nelarabine: two new purine nucleoside analogs. Curr Opin Oncol. 2006 Nov;18(6):584-90. doi: 10.1097/01.cco.0000245326.65152.af. PMID: 16988579. 16: Jhaveri KD, Chidella S, Allen SL, Fishbane S. Clofarabine-induced kidney toxicity. J Oncol Pharm Pract. 2014 Aug;20(4):305-8. doi: 10.1177/1078155213504976. Epub 2013 Sep 29. PMID: 24081220. 17: Ghanem H, Kantarjian H, Ohanian M, Jabbour E. The role of clofarabine in acute myeloid leukemia. Leuk Lymphoma. 2013 Apr;54(4):688-98. doi: 10.3109/10428194.2012.726722. Epub 2012 Sep 28. PMID: 22957815; PMCID: PMC5681218. 18: Huguet F, Leguay T, Raffoux E, Rousselot P, Vey N, Pigneux A, Ifrah N, Dombret H. Clofarabine for the treatment of adult acute lymphoid leukemia: the Group for Research on Adult Acute Lymphoblastic Leukemia intergroup. Leuk Lymphoma. 2015 Apr;56(4):847-57. doi: 10.3109/10428194.2014.887708. PMID: 24996442. 19: Larson ML, Venugopal P. Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009 Jun;10(8):1353-7. doi: 10.1517/14656560902997990. PMID: 19463072. 20: Jeha S, Kantarjian H. Clofarabine for the treatment of acute lymphoblastic leukemia. Expert Rev Anticancer Ther. 2007 Feb;7(2):113-8. doi: 10.1586/14737140.7.2.113. PMID: 17288522.

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(R)-ZG197

(R)-ZG197