WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 100180
Description: 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.
MedKoo Cat#: 100180
Chemical Formula: C10H11ClFN5O3
Exact Mass: 303.05345
Molecular Weight: 303.68
Elemental Analysis: C, 39.55; H, 3.65; Cl, 11.67; F, 6.26; N, 23.06; O, 15.81
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: >98% (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
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.
|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|
1: Stumpel DJ, Schneider P, Pieters R, Stam RW. The potential of clofarabine in MLL-rearranged infant acute lymphoblastic leukaemia. Eur J Cancer. 2015 Jul 15. pii: S0959-8049(15)00643-7. doi: 10.1016/j.ejca.2015.06.117. [Epub ahead of print] PubMed PMID: 26188848.
2: Rudrapatna VK, Morley K, Boucher KM, Pierson AS, Shull CT, Kushner JP, Shami PJ. Phase I trial of low-dose oral Clofarabine in myelodysplastic syndromes patients who have failed frontline therapy. Leuk Res. 2015 Aug;39(8):835-9. doi: 10.1016/j.leukres.2015.05.004. Epub 2015 May 18. PubMed PMID: 26038120.
3: Loeffler C, Kapp M, Grigoleit GU, Mielke S, Loeffler J, Heuschmann PU, Malzahn U, Hupp E, Einsele H, Stuhler G. Control of relapsed or refractory acute myeloid leukemia by clofarabine in preparation for allogeneic stem cell transplant. Leuk Lymphoma. 2015 Jun 19:1-5. [Epub ahead of print] PubMed PMID: 26014275.
4: Buckley SA, Mawad R, Gooley TA, Becker PS, Sandhu V, Hendrie P, Scott BL, Wood BL, Walter RB, Smith K, Dean C, Estey EH, Pagel JM. A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age. Br J Haematol. 2015 Aug;170(3):349-55. doi: 10.1111/bjh.13437. Epub 2015 Apr 8. PubMed PMID: 25854284.
5: Kadia TM, Faderl S, Ravandi F, Jabbour E, Garcia-Manero G, Borthakur G, Ferrajoli A, Konopleva M, Burger J, Huang X, Wang X, Pierce S, Brandt M, Feliu J, Cortes J, Kantarjian H. Final results of a phase 2 trial of clofarabine and low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia. Cancer. 2015 Jul 15;121(14):2375-82. doi: 10.1002/cncr.29367. Epub 2015 Mar 25. PubMed PMID: 25809968.
6: Patel YT, Jacus MO, Boulos N, Dapper JD, Davis AD, Vuppala PK, Freeman BB 3rd, Mohankumar KM, Throm SL, Gilbertson RJ, Stewart CF. Preclinical examination of clofarabine in pediatric ependymoma: intratumoral concentrations insufficient to warrant further study. Cancer Chemother Pharmacol. 2015 May;75(5):897-906. doi: 10.1007/s00280-015-2713-z. Epub 2015 Feb 28. PubMed PMID: 25724157; PubMed Central PMCID: PMC4420645.
7: Valdez BC, Li Y, Murray D, Ji J, Liu Y, Popat U, Champlin RE, Andersson BS. Comparison of the cytotoxicity of cladribine and clofarabine when combined with fludarabine and busulfan in AML cells: Enhancement of cytotoxicity with epigenetic modulators. Exp Hematol. 2015 Jun;43(6):448-461.e2. doi: 10.1016/j.exphem.2015.02.001. Epub 2015 Feb 19. PubMed PMID: 25704054; PubMed Central PMCID: PMC4458397.
8: Zoellner AK, Fritsch S, Prevalsek D, Engel N, Hubmann M, Reibke R, Rieger CT, Hellmuth JC, Haas M, Mumm F, Herold T, Ledderose G, Hiddemann W, Dreyling M, Hausmann A, Tischer J. Sequential therapy combining clofarabine and T-cell-replete HLA-haploidentical haematopoietic SCT is feasible and shows efficacy in the treatment of refractory or relapsed aggressive lymphoma. Bone Marrow Transplant. 2015 May;50(5):679-84. doi: 10.1038/bmt.2014.328. Epub 2015 Feb 2. PubMed PMID: 25642765.
9: Roberts DA, Wadleigh M, McDonnell AM, DeAngelo DJ, Stone RM, Steensma DP. Low efficacy and high mortality associated with clofarabine treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes. Leuk Res. 2015 Feb;39(2):204-10. doi: 10.1016/j.leukres.2014.11.031. Epub 2014 Dec 12. PubMed PMID: 25554239.
10: Becker PS, Medeiros BC, Stein AS, Othus M, Appelbaum FR, Forman SJ, Scott BL, Hendrie PC, Gardner KM, Pagel JM, Walter RB, Parks C, Wood BL, Abkowitz JL, Estey EH. G-CSF priming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm. Am J Hematol. 2015 Apr;90(4):295-300. doi: 10.1002/ajh.23927. Epub 2015 Jan 30. PubMed PMID: 25545153.
ClolarÂ® (clofarabine) injection contains clofarabine, a purine nucleosideanti-metabolite. ClolarÂ® (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.