Gemcitabine elaidate
(Synonyms: 反油酸吉西他滨; CP-4126; CO-101; Gemcitabine 5'-elaidate) 目录号 : GC36130
A prodrug form of gemcitabine
Cas No.:210829-30-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Gemcitabine elaidate is a lipophilic prodrug form of the nucleoside analog gemcitabine that contains an elaidic acid moiety.1 Gemcitabine elaidate inhibits growth of gemcitabine-sensitive L1210/L5, BCLO, and A2780 cells (IC50s = 0.0033, 0.0042, and 0.0025 ?M, respectively) but not cytarabine-resistant L4A6 and Bara-C cells (IC50s = 16 and 13 ?M, respectively) or gemcitabine-resistant AG6000 cells (IC50 = 91 ?M). It inhibits growth of THX, LOX, MOLT-4, and MOLT-4/C8 cells in a manner independent of nucleoside transport. Gemcitabine elaidate reduces tumor growth in EKVX non-small cell lung cancer and MHMX sarcoma mouse xenograft models but not in an H-146 small cell lung cancer mouse xenograft model when administered at a dose of 40 mg/kg every three days.
1.Bergman, A.M., Adema, A.D., Balzarini, J., 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 modelsInvest. New Drugs29(3)456-466(2011)
| Cas No. | 210829-30-4 | SDF | |
| 别名 | 反油酸吉西他滨; CP-4126; CO-101; Gemcitabine 5'-elaidate | ||
| Canonical 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 | ||
| 分子式 | C27H43F2N3O5 | 分子量 | 527.64 |
| 溶解度 | DMSO: ≥ 26 mg/mL (49.28 mM); Water: < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8952 mL | 9.4762 mL | 18.9523 mL |
| 5 mM | 0.379 mL | 1.8952 mL | 3.7905 mL |
| 10 mM | 0.1895 mL | 0.9476 mL | 1.8952 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Palmitoyl Carnitine-Anchored Nanoliposomes for Neovasculature-Specific Delivery of Gemcitabine elaidate to Treat Pancreatic Cancer
Cancers (Basel) 2022 Dec 28;15(1):182.PMID:36612178DOI:10.3390/cancers15010182.
Being the fourth most fatal malignancy worldwide, pancreatic cancer is on track to become the second leading cause of cancer-related deaths in the United States by 2030. Gemcitabine is a first-line chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC). Gemcitabine elaidate (Gem Elaidate) is a lipophilic derivative which allows hENT1-independent intracellular delivery of gemcitabine and better pharmacokinetics and entrapment in a nanocarrier. Cancer cells and neovasculature are negatively charged compared to healthy cells. Palmitoyl-DL-carnitine chloride (PC) is a Protein kinase C (PKC) inhibitor which also provides a cationic surface charge to nanoliposomes for targeting tumor neovasculature and augmented anticancer potency. The objectives of our study are: (a) to develop and characterize a PKC inhibitor-anchored Gem Elaidate-loaded PEGylated nanoliposome (PGPLs) and (b) to investigate the anticancer activity of Gem Elaidate and PGPLs in 2D and 3D models of pancreatic cancer. The optimized PGPLs resulted in a particle size of 80 ± 2.31 nm, a polydispersity index of 0.15 ± 0.05 and a ζ-potential of +31.6 ± 3.54 mV, with a 93.25% encapsulation efficiency of Gem Elaidate in PGPLs. Our results demonstrate higher cellular uptake, inhibition in migration, as well as angiogenesis potential and significant apoptosis induced by PGPLs in 3D multicellular tumor spheroids of pancreatic cancer cells. Hence, PGPLs could be an effective and novel nanoformulation for the neovasculature-specific delivery of Gemcitabine elaidate to treat PDAC.
Wirelessly Activated Nanotherapeutics for In Vivo Programmable Photodynamic-Chemotherapy of Orthotopic Bladder Cancer
Adv Sci (Weinh) 2022 May;9(16):e2200731.PMID:35393785DOI:10.1002/advs.202200731.
Photochemical internalization (PCI) is a promising intervention using photodynamic therapy (PDT) to enhance the activity of chemotherapeutic drugs. However, current bladder cancer treatments involve high-dose chemotherapy and high-irradiance PDT which cause debilitating side effects. Moreover, low penetration of light and drugs in target tissues and cumbersome light delivery procedures hinder the clinical utility of PDT and chemotherapy combination for PCI. To circumvent these challenges, a photodynamic-chemotherapy approach is developed comprising tumor-targeting glycosylated nanocarriers, coloaded with chlorin e6 (Ce6) and Gemcitabine elaidate (GemE), and a miniaturized implantable wirelessly powered light-emitting diode (LED) as a light source. The device successfully delivers four weekly light doses to the bladder while the nanocarrier promoted the specific accumulation of drugs in tumors. This approach facilitates the combination of low-irradiance PDT (1 mW cm-2 ) and low-dose chemotherapy (≈1500× lower than clinical dose) which significantly cures and controls orthotopic disease burden (90% treated vs control, 35%) in mice, demonstrating a potential new bladder cancer treatment option.
Tumor-targeting albumin nanoparticles as an efficacious drug delivery system and potential diagnostic tool in non-muscle-invasive bladder cancer therapy
Nanomedicine 2022 Nov;46:102600.PMID:36064034DOI:10.1016/j.nano.2022.102600.
Current intravesical chemotherapy for non-muscle invasive bladder cancer (NMIBC) has limited efficacy due to loss of the instilled agent from urine voiding and the agent's lack of specificity for the tumors. We developed a nanocarrier (txCD47-HNP, ∼100 nm) based on human serum albumin conjugated with a peptide that targets the cluster of differentiation 47 receptor overexpressed on bladder cancer (BC) cells. The IC50 of Gemcitabine elaidate (GEM) loaded in the txCD47-HNP was almost an order of magnitude lower than that of free GEM. In a mouse orthotopic BC model, GEM loaded in txCD47-HNP effectively reduced the tumor burden. Tumor cells in BC patients' urine can also be targeted by fluorescence-labeled txCD47-HNP resulting in >83 % of the cells exhibiting fluorescence. Thus, txCD47-HNP can potentially be a theranostic agent in NMIBC management by serving as a targeted drug delivery vehicle as well as an alternative to urine cytology.
A first-in-human phase I and pharmacokinetic study of CP-4126 (CO-101), a nucleoside analogue, in patients with advanced solid tumours
Cancer Chemother Pharmacol 2015 Oct;76(4):785-92.PMID:26289594DOI:10.1007/s00280-015-2846-0.
Background: CP-4126 (Gemcitabine elaidate, previously CO-101) is a lipid-drug conjugate of gemcitabine designed to circumvent human equilibrative nucleoside transporter1-related resistance to gemcitabine. The purpose of this study was to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) of CP-4126, and to describe its pharmacokinetic profile. Methods: Eligible patients with advanced refractory solid tumours, and adequate performance status, haematological, renal and hepatic function, were treated with one of escalating doses of CP-4126 administered by a 30-min intravenous infusion on days 1, 8 and 15 of a 28-day cycle. Blood and urine samples were collected to determine the pharmacokinetics (PKs) of CP-4126. Results: Forty-three patients, median age 59 years (range 18-76; male = 27, female = 16), received one of ten dose levels (30-1600 mg/m(2)). Dose-limiting toxicities included grade 3 anaemia, grade 3 fatigue and grade 3 elevation of transaminases. The MTD and RP2D were 1250 mg/m(2) on basis of the toxicity and PK data. CP-4126 followed dose-dependent kinetics and maximum plasma concentrations occurred at the end of CP-4126 infusion. Seven patients achieved stable disease sustained for ≥3 months, including two patients with pancreatic cancer who had progressed on or after gemcitabine exposure. Conclusions: CP-4126 was well tolerated with comparable toxicity profile to gemcitabine. Future studies are required to determine its anti-tumour efficacy, either alone or in combination with other cytotoxic chemotherapy regimens.
Statin treatment and outcomes of metastatic pancreatic cancer: a pooled analysis of two phase III studies
Clin Transl Oncol 2019 Jun;21(6):810-816.PMID:30465184DOI:10.1007/s12094-018-1992-3.
Background: The current analysis aims to evaluate the impact of statin co-treatment on the survival of patients with metastatic pancreatic cancer. Methods: This is a pooled analysis of de-identified patient data from two clinical trials (NCT01124786; NCT00844649). Overall and progression-free survival according to patient subsets (patients who received or who did not receive statins) were assessed through Kaplan-Meier analysis and log-rank test. Univariate and multivariate Cox regression analysis was performed to evaluate different factors potentially affecting overall and progression-free survival. Propensity score matching was performed to address heterogeneity in baseline characteristics of different subgroups of patients. Results: A total of 797 patients were assessed in the current study; of which 156 patients received statins and 641 did not receive statins. Using Kaplan-Meier survival estimates, patients who received statins seem to have better overall and progression-free survival compared to patients who did not (P = 0.008; P < 0.001, respectively). In multivariate analysis for factors affecting overall survival, the following factors were associated with worse overall survival: worse performance status (P < 0.001), no statin use (P = 0.044) and multiple sites of metastatic disease (P = 0.023); likewise in multivariate analysis for factors affecting progression-free survival, the following factors were associated with worse progression-free survival: worse performance status (P < 0.001), Gemcitabine elaidate chemotherapy (P = 0.015) and no statin use (P = 0.048). Following propensity score matching and using Kaplan-Meier estimates, statin use was also associated with better overall and progression-free survival (P = 0.005; P = 0.040, respectively). Conclusion: Statin use seems to be associated with better overall survival among patients with metastatic pancreatic cancer treated with first-line chemotherapy. Prospective studies designed specifically to assess this potential effect of statins are needed.