Gemcitabine elaidate (formerly know as CP4126; CO101; CP-4126; CO-101) is a potent, lipophilic, unsaturated fatty acid ester derivative and prodrug form of gemcitabine (dFdC), which is an antimetabolite deoxynucleoside analogue with potential antitumor activity. Gemcitabine, the prodrug, is hydrolyzed intracellularly by esterases, converting it into the active metabolites difluorodeoxycytidine di- and tri-phosphate (dFdCDP and dFdCTP) by deoxycytidine kinase. Because dFdCDP inhibits ribonucleotide reductase, less deoxynucleotide is available for DNA synthesis. When dFdCTP is incorporated into DNA, DNA strand termination and apoptosis occur.
Physicochemical Properties
| Molecular Formula | C27H43N3O5F2 |
| Molecular Weight | 527.64422 |
| Exact Mass | 527.317 |
| Elemental Analysis | C, 61.46; H, 8.21; F, 7.20; N, 7.96; O, 15.16 |
| CAS # | 210829-30-4 |
| Related CAS # | 95058-81-4; 122111-03-9 (HCl); 116371-67-6 (Gemcitabine monophosphate free acid); 1638288-31-9 (Gemcitabine monophosphate disodium salt); 840506-29-8 [Acelarin (NUC-1031) is a ProTide transformation and enhancement of the widely-used nucleoside analogue, gemcitabine]; 892128-60-8 (LY2334737, an orally bioavailable prodrug of gemcitabine) |
| PubChem CID | 9828310 |
| Appearance | White solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 631.4±65.0 °C at 760 mmHg |
| Flash Point | 335.7±34.3 °C |
| Vapour Pressure | 0.0±4.2 mmHg at 25°C |
| Index of Refraction | 1.536 |
| LogP | 7.7 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 19 |
| Heavy Atom Count | 37 |
| Complexity | 803 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | O[C@@H](C(F)(F)[C@H](N1C(N=C(C=C1)N)=O)O2)[C@H]2COC(CCCCCCC/C=C/CCCCCCCC)=O |
| InChi Key | HESSNRGIEVBPRB-QDDPNBLJSA-N |
| InChi Code | InChI=1S/C27H43F2N3O5/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-23(33)36-20-21-24(34)27(28,29)25(37-21)32-19-18-22(30)31-26(32)35/h9-10,18-19,21,24-25,34H,2-8,11-17,20H2,1H3,(H2,30,31,35)/b10-9+/t21-,24-,25-/m1/s1 |
| Chemical Name | [(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methyl (E)-octadec-9-enoate |
| Synonyms | Gemcitabine elaidate; CO101; CP4126; CO-101; CP-4126; CO 101; CO-101; Gemcitabine (elaidate); CP-4126 (LVT DERIVATIVE OF GEMCITABINE); CO-1.01; 231C73W7LG; CP 4126 |
| 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
| Targets | DNA synthesis |
| ln Vitro | Gemcitabine elaidate (0.2 nM-1 mM; 72 h) inhibits the growth of cells that are sensitive to and resistant to gemcitabine. For L1210/L5, L4A6, BCLO, Bara-C, C26-A, C26-G, A2780, AG6000, THX, LOX, MOLT4, and MOLT4/C8 cells, the IC50s are 0.0033, 16.0, 0.0042, 13.0, 0.0015, 0.03, 0.0025, 91, 0.0040, 0.028, and 0.088 μM, respectively[1]. Gemcitabine elaidate (0.5 nM-1 μM; 72 h) increases S phase accumulation and dose-dependent cell death in A549 and WiDR cells[2]. |
| ln Vivo |
Gemcitabine elaidate (25–120 mg/kg; i.p. every 3 days for 5 doses) inhibits the growth of certain solid tumor xenografts, including fibrous histiocytoma (TAX II–1), non-small cell lung cancer (EKVX), non-classifiable sarcoma (MHMX), malignant melanoma (THX), prostate cancer (CRL–1435), and pancreatic cancer (PANC-1)[1]. Gemcitabine elaidate (10–20 mg/kg; p.o. every 3 days for 5 doses) exhibits respectable toxicity and notable antitumor activity in the colon cancer xenograft Co6044 bearing mice[1]. Gemcitabine elaidate (p.o. once daily for 5 doses) exhibits favorable toxicity and antitumor activity; however, the 15 mg/kg dose is highly toxic in the human colon cancer xenograft Co6044[1]. |
| Cell Assay |
Cell Line: A549 and WiDR cells Concentration: 0.0005, 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1.0 μM Incubation Time: 72 h Result: Induced a G2/M and S phase accumulation. |
| Animal Protocol |
Female BALB/c nude (nu/nu) mice (5-8 weeks; 20-27 g) were bearing tumor of EKVX, H-146, MHMX, TAX II-1, OHS, THX, MA-11, CRL-1435, PANC-1 and MiaPaCa-2, respectively 25-120 mg/kg I.p. every 3 days for 5 doses |
| References |
[1]. Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models. Invest New Drugs. 2011 Jun;29(3):456-66. [2]. Cell cycle effects of fatty acid derivatives of cytarabine, CP-4055, and of gemcitabine, CP-4126, as basis for the interaction with oxaliplatin and docetaxel. Int J Oncol. 2010 Jan;36(1):285-94. |
| Additional Infomation |
Gemcitabine elaidate is a pyrimidine 2'-deoxyribonucleoside. Gemcitabine elaidate has been used in trials studying the treatment of Solid Tumor, Lung Cancer, Non-small-cell Lung Cancer, and Metastatic Pancreatic Adenocarcinoma. Gemcitabine Elaidate is a lipophilic, unsaturated fatty acid ester derivative of gemcitabine (dFdC), an antimetabolite deoxynucleoside analogue, with potential antineoplastic activity. Upon hydrolysis intracellularly by esterases, the prodrug gemcitabine is converted into the active metabolites difluorodeoxycytidine di- and tri-phosphate (dFdCDP and dFdCTP) by deoxycytidine kinase. dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis; dFdCTP is incorporated into DNA, resulting in DNA strand termination and apoptosis. Due to its lipophilicity, gemcitabine 5'-elaidic acid ester exhibits an increased cellular uptake and accumulation, resulting in an increased conversion to active metabolites, compared to gemcitabine. In addition, this formulation of gemcitabine may be less susceptible to deamination and deactivation by deoxycytidine deaminase. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 100 mg/mL (~189.52 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.74 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 25.0 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: 2.5 mg/mL (4.74 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.74 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 25.0 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 | 1.8952 mL | 9.4762 mL | 18.9523 mL | |
| 5 mM | 0.3790 mL | 1.8952 mL | 3.7905 mL | |
| 10 mM | 0.1895 mL | 0.9476 mL | 1.8952 mL |