Repositioning Candidate Details
| Candidate ID: | R0224 |
| Source ID: | DB00631 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Clofarabine |
| Synonyms: | (2R,3R,4S,5R)-5-(6-amino-2-chloropurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol; 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine; 2-chloro-9-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)adenine; CAFdA; Cl-F-Ara-A |
| Molecular Formula: | C10H11ClFN5O3 |
| SMILES: | [H][C@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C=NC2=C(N)N=C(Cl)N=C12 |
| Structure: |
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| DrugBank Description: | Clofarabine is a purine nucleoside antimetabolite that is being studied in the treatment of cancer. It is marketed as Clolar in the U.S. and Canada, or Evoltra in Europe, Australia, and New Zealand. Clofarabine is used in paediatrics to treat a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia (ALL), only after at least two other types of treatment have failed. It is not known if the drug extends life expectancy. Its potential use in acute myeloid leukaemia (AML) and juvenile myelomonocytic leukaemia (JMML) has been investigated. |
| CAS Number: | 123318-82-1 |
| Molecular Weight: | 303.677 |
| DrugBank Indication: | For the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphocytic (lymphoblastic) leukemia after at least two prior regimens. It is designated as an orphan drug by the FDA for this use. |
| DrugBank Pharmacology: | Clofarabine is a purine nucleoside antimetabolite that differs from other puring nucleoside analogs by the presence of a chlorine in the purine ring and a flourine in the ribose moiety. Clofarabine seems to interfere with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by clofarabine, other effects also occur. Clofarabine prevents cells from making DNA and RNA by interfering with the synthesis of nucleic acids, thus stopping the growth of cancer cells. |
| DrugBank MoA: | Clofarabine is metabolized intracellularly to the active 5'-monophosphate metabolite by deoxycytidine kinase and 5'-triphosphate metabolite by mono- and di-phospho-kinases. This metabolite inhibits DNA synthesis through an inhibitory action on ribonucleotide reductase, and by terminating DNA chain elongation and inhibiting repair through competitive inhibition of DNA polymerases. This leads to the depletion of the intracellular deoxynucleotide triphosphate pool and the self-potentiation of clofarabine triphosphate incorporation into DNA, thereby intensifying the effectiveness of DNA synthesis inhibition. 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. |
| Targets: | DNA polymerase alpha catalytic subunit inhibitor; Ribonucleoside-diphosphate reductase large subunit inhibitor; DNA other/unknown |
| Inclusion Criteria: | Therapeutic strategy associated |
