Size | Price | Stock | Qty |
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5mg |
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10mg |
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50mg |
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100mg |
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Other Sizes |
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Targets |
DNA synthesis
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ln Vitro |
Gemcitabine elaidate (0.2 nM-1 mM; 72 h) hydrochloride is useful against L1210/L5, L4A6, BCLO, Bara-C, C26-A, C26-G, A2780, AG6000, THX, and other cells that are susceptible to or resistant to gemcitabine. For LOX, MOLT4, and MOLT4/C8 cells, the corresponding IC50 values are 0.0033, 16.0, 0.0042, 13.0, 0.0015, 0.03, 0.0025, 91, 0.0040, 0.0077, 0.028, and 0.088 μM [1]. A549 and WiDR cell death is dose-dependent and increases with gemcitabine elaidate hydrochloride (0.5 nM-1 μM; 72 hours) [2].
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ln Vivo |
Gemcitabine elaidate hydrochloride (ip every 3 days for 5 doses; 25–120 mg/kg) inhibits solid tumor xenografts in malignant melanoma (THX), fibrous histiocytoma (TAX II–), sarcoma unclassifiable (MHMX), non-small cell lung cancer (EKVX), prostate cancer (CRL-1435), and pancreatic cancer (PANC-1) [1]. In Co6044 colon cancer xenograft mice, gemcitabine elaidate hydrochloride (10–20 mg/kg; po every 3 days for 5 doses) showed respectable toxicity and noteworthy antitumor efficacy [1]. When applied topically once daily for five doses, gemcitabine elaidate hydrochloride demonstrated good antitumor efficacy and toxicity, with a dose of 15 mg/kg being extremely lethal against the human colon cancer xenograft Co6044 [1].
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Cell Assay |
Cell Cycle Analysis[2]
Cell Types: A549 and WiDR cells Tested Concentrations: 0.0005, 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1.0 μM Incubation Duration: 72 h Experimental Results: Induced a G2/M and S phase accumulation. |
Animal Protocol |
Animal/Disease Models: 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[1]
Doses: 25-120 mg/kg Route of Administration: Ip every 3 days for 5 doses Experimental Results: Inhibited the growth of EKVX, MHMX, TAX II-1, THX, CRL-1435 and PANC-1, with T/C values of 7%, 1%, 30%, 7%, 9%, and 12%, respectively. |
References |
[1]. Bergman AM, et, al. 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]. Adema AD, et, al. 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 is a deoxycytidine (dCyd) analog with activity in leukemia and solid tumors, which requires phosphorylation by deoxycytidine kinase (dCK). Decreased membrane transport is a mechanism of resistance to gemcitabine. In order to facilitate gemcitabine uptake and prolong retention in the cell, a lipophilic pro-drug was synthesized (CP-4126), with an elaidic fatty acid esterified at the 5'position. CP-4126 was tested in cell lines resistant to cytarabine, another dCyd analog or gemcitabine. Activity of gemcitabine and the derivative was comparable in the parent cell lines, while in dCK deficient cells all compounds were inactive. However, inhibition of nucleoside transport increased the IC(50) for gemcitabine up to 200-fold, but not for CP-4126, underlining the independence of a nucleoside transporter. For in vivo evaluation, nude mice bearing a human xenograft were treated intraperitoneally every third day for five doses at the maximal tolerated dose. In melanoma, sarcoma, lung, prostate, pancreatic and breast cancer xenografts, gemcitabine and CP-4126 were equally and highly effective; in four other xenografts moderately but equally active. In contrast to gemcitabine, CP-4126 could be administered orally, with a schedule and dose dependent toxicity and antitumor activity. In a colon cancer xenograft, antitumor activity of orally administered CP-4126 was equal to the intraperitoneally administered drug. In conclusion, CP-4126 is membrane transporter independent. Intraperitoneally administered CP-4126 was as effective as gemcitabine in several xenografts and CP-4126 is tolerated when orally administered. CP-4126 seems to be a promising new anticancer drug.[1]
To bypass resistance due to limited entry into the cell derivatives of cytarabine (CP-4055, elacytarabine) and gemcitabine (CP-4126) containing a fatty acid chain at the 5' position of the nucleoside were developed. CP-4055 showed an increased retention of the active metabolite, the triphosphate. This characteristic was supposed to favor combinations, such as with the tubulin antagonist docetaxel, the platinum oxaliplatin and the antifolate pemetrexed. The role of the cell cycle effects of CP-4055 and CP-4126 on the efficacy of the combination with docetaxel or pemetrexed was determined. The combination of CP-4055 with oxaliplatin and docetaxel was also evaluated in a mouse xenograft model. CP-4055 induced a G2/M and S phase accumulation and CP-4126 an S phase accumulation. Both analogs induced a dose-dependent cell kill (apoptosis and necrosis). None of the docetaxel combinations induced a synergistic effect. The combination of docetaxel with CP-4055 or CP-4126 induced a G2/M accumulation in the A549 (lung cancer) cell line, but a G0/G1 accumulation in the WiDR (colon cancer) cell line. Preincubation with docetaxel induced an increased cell kill in both cell lines. The combination with oxaliplatin showed a synergistic effect in both cell lines. Combinations with pemetrexed were antagonistic in both cell lines. In the A549 cell line pemetrexed with CP-4055 led to an increase of the G0/G1 phase and the S phase. In WiDR the combination of pemetrexed with CP-4055 increased the G0/G1 phase and increased the cell kill. Pemetrexed with CP-4126 induced an increase in the G0/G1 phase and the S phase in the A549 cell line. In the xenograft study, on a colon cancer and a lung metastasis model, the combination of CP-4055 with docetaxel showed the best results. Treatment with CP-4055 followed by docetaxel after 4 h resulted in a reduction in metastasis in a lung metastasis model, and a favorable toxicity profile was observed. In conclusion, the combinations with oxaliplatin showed a synergistic effect in the combination studies. Although the combinations with docetaxel did not show an enhanced effect in the in vitro studies, this combination revealed an increased effect in the xenograft model.[2] |
Molecular Formula |
C27H44CLF2N3O5
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Molecular Weight |
564.11
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Exact Mass |
563.29375
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CAS # |
2918768-08-6
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Related CAS # |
Gemcitabine elaidate;210829-30-4
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Appearance |
White to off-white solid powder
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tPSA |
114Ų
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InChi Key |
LYTHDWBFDKMMPL-SDCWGXALSA-N
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InChi Code |
InChI=1S/C27H43F2N3O5.ClH/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);1H/b10-9+;/t21-,24-,25-;/m1./s1
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Chemical Name |
[(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methyl (E)-octadec-9-enoate;hydrochloride
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Synonyms |
Gemcitabine elaidate hydrochloride; Gemcitabine elaidate (hydrochloride); 2918768-08-6; CO-101 hydrochloride; EX-A8562;
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : 100 mg/mL (177.27 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.43 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 | 1.7727 mL | 8.8635 mL | 17.7270 mL | |
5 mM | 0.3545 mL | 1.7727 mL | 3.5454 mL | |
10 mM | 0.1773 mL | 0.8864 mL | 1.7727 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.