Elacytarabine (also known as CP 4055; CP-4055), an antineoplastic drug, is a lipid-conjugated (5'-elaidic acid ester) derivative and a prodrug of the nucleoside analog cytarabine (arabinoside; Ara-C). Elacytarabine exhibits antitumor properties. As a prodrug, CP-4055 is intracellularly converted by deoxycytidine kinase into cytarabine triphosphate, which then inhibits DNA synthesis by competing with cytidine for DNA incorporation. When CP-4055 is compared to cytarabine, it exhibits higher absorption and retention in cells, which leads to higher activation of cytarabine triphosphate by deoxycytidine kinase, lower deamination and deactivation by deoxycytidine deaminase, and higher inhibition of DNA synthesis. In addition to inhibiting RNA synthesis, this agent has an effect that cytarabine does not.
Physicochemical Properties
| Molecular Formula | C27H45N3O6 |
| Molecular Weight | 507.6627 |
| Exact Mass | 507.331 |
| CAS # | 188181-42-2 |
| PubChem CID | 6438895 |
| Appearance | White to off-white solid powder |
| LogP | 4.367 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 19 |
| Heavy Atom Count | 36 |
| Complexity | 754 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | CCCCCCCC/C=C/CCCCCCCC(=O)OC[C@@H]1[C@H]([C@@H]([C@@H](O1)N2C=CC(=NC2=O)N)O)O |
| InChi Key | FLFGNMFWNBOBGE-FNNZEKJRSA-N |
| InChi Code | InChI=1S/C27H45N3O6/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-23(31)35-20-21-24(32)25(33)26(36-21)30-19-18-22(28)29-27(30)34/h9-10,18-19,21,24-26,32-33H,2-8,11-17,20H2,1H3,(H2,28,29,34)/b10-9+/t21-,24-,25+,26-/m1/s1 |
| Chemical Name | [(2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl (E)-octadec-9-enoate |
| Synonyms | Elacytarabine; CP 4055 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| References |
[1]. Elacytarabine (CP-4055) in the treatment of acute myeloid leukemia. Future Oncol. 2013 Aug;9(8):1073-82. |
| Additional Infomation |
Elacytarabine is a pyrimidine nucleoside. Elacytarabine is a fatty acid derivative of [cytarabine], an approved cytotoxic cancer drug. Cytarabine has limitations such as minimal uptake in solid tumours and is only used to treat leukaemia. Elacytarabine is designed to overcome this limitation and has shown considerable uptake in solid tumour cells. Elacytarabine is a patented new chemical entity of the nucleoside analog class, with improved biological properties and the potential to treat solid tumours such as non-small cell lung cancer, malignant melanoma and ovarian cancer. Elacytarabine is the lipophilic 5'-elaidic acid ester of the deoxycytidine analog cytosine arabinoside (cytarabine; Ara-C) with potential antineoplastic activity. As a prodrug, elacytarabine is converted intracellularly into cytarabine triphosphate by deoxycytidine kinase and subsequently competes with cytidine for incorporation into DNA, thereby inhibiting DNA synthesis. Compared to cytarabine, elacytarabine shows increased cellular uptake and retention, resulting in increased activation by deoxycytidine kinase to cytarabine triphosphate, decreased deamination and deactivation by deoxycytidine deaminase, and increased inhibition of DNA synthesis. This agent also inhibits RNA synthesis, an effect not seen with cytarabine. Drug Indication Investigated for use/treatment in leukemia (unspecified) and melanoma. Treatment of acute myeloid leukaemia Mechanism of Action CP-4055 is the lipophilic 5'-elaidic acid ester of the deoxycytidine analog cytosine arabinoside (cytarabine; Ara-C) with potential antineoplastic activity. As a prodrug, CP-4055 is converted intracellularly into cytarabine triphosphate by deoxycytidine kinase and subsequently competes with cytidine for incorporation into DNA, thereby inhibiting DNA synthesis. Compared to cytarabine, CP-4055 shows increased cellular uptake and retention, resulting in increased activation by deoxycytidine kinase to cytarabine triphosphate, decreased deamination and deactivation by deoxycytidine deaminase, and increased inhibition of DNA synthesis. This agent also inhibits RNA synthesis, an effect not seen with cytarabine. Pharmacodynamics CP-4055 is a fatty acid derivative of cytarabine, an approved cytotoxic cancer drug. Cytarabine has limitations such as minimal uptake in solid tumours and is only used to treat leukaemia. CP-4055 is designed to overcome this limitation and has shown considerable uptake in solid tumour cells. CP-4055 is a patented new chemical entity of the nucleoside analog class, with improved biological properties and the potential to treat solid tumours such as non-small cell lung cancer, malignant melanoma and ovarian cancer. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~125 mg/mL (~246.2 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9698 mL | 9.8491 mL | 19.6982 mL | |
| 5 mM | 0.3940 mL | 1.9698 mL | 3.9396 mL | |
| 10 mM | 0.1970 mL | 0.9849 mL | 1.9698 mL |