Gemcitabine elaidate
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MedKoo CAT#: 204970

CAS#: 210829-30-4

Description: Gemcitabine elaidate, also known as CO-101 and CP-4126, 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.

Chemical Structure

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Gemcitabine elaidate
CAS# 210829-30-4
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 204970
Name: Gemcitabine elaidate
CAS#: 210829-30-4
Chemical Formula: C27H43F2N3O5
Exact Mass: 527.32
Molecular Weight: 527.644
Elemental Analysis: C, 61.46; H, 8.21; F, 7.20; N, 7.96; O, 15.16

Price and Availability

Size Price Availability Quantity
5mg USD 120 Ready to ship
10mg USD 200 Ready to ship
25mg USD 450 Ready to ship
50mg USD 750 Ready to ship
100mg USD 1350 Ready to ship
200mg USD 2250 Ready to ship
Bulk inquiry

Synonym: CO101; CO-101; CO 101; CP4126; CP-4126; CP 4126; Gemcitabine elaidate.

IUPAC/Chemical Name: (E)-((2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4,4-difluoro-3-hydroxytetrahydrofuran-2-yl)methyl octadec-9-enoate.

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

SMILES Code: CCCCCCCC/C=C/CCCCCCCC(OC[C@H]1O[C@@H](N2C=CC(N)=NC2=O)C(F)(F)[C@@H]1O)=O

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: CO-101 is a new, patented, cytotoxic drug which consists of gemcitabine, an anticancer nucleoside analog, coupled to a fatty acid chain. CO-101 was designed to improve upon the efficacy of gemcitabine by enabling the drug to enter cancer cells without requiring uptake by a specific transporter molecule. Intravenous CO-101 is currently being evaluated in a clinical trial in advanced pancreatic cancer. Gemcitabine is the current standard treatment for advanced pancreatic cancer, and is also used in combination with other chemotherapy agents for the treatment of other cancers, including ovarian, non-small cell lung, and breast cancer. As a hydrophilic molecule, the entry of gemcitabine into tumor cells is dependent upon the expression of specific membrane transporter proteins, particularly hENT1. (source: http://www.clovisoncology.com/products/prod_co101.php).   Chemical structure of gemcitabine        

Biological target: Gemcitabine elaidate inhibits growth of L1210/L5, BCLO, and A2780 cells with IC50s of 0.0033, 0.0042, and 0.0025 µM, respectively.
In vitro activity: 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. Reference: Invest New Drugs. 2011 Jun;29(3):456-66. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076580/
In vivo activity: 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. Reference: Invest New Drugs. 2011 Jun;29(3):456-66. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076580/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Ethanol:PBS (pH 7.2) (1:2) 0.3 0.63
DMSO 28.0 53.07
DMF 30.0 56.86
Ethanol 30.0 56.86

Preparing Stock Solutions

The following data is based on the product molecular weight 527.64 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Bergman AM, Adema AD, Balzarini J, Bruheim S, Fichtner I, Noordhuis P, Fodstad O, Myhren F, Sandvold ML, Hendriks HR, Peters GJ. 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. doi: 10.1007/s10637-009-9377-7. Epub 2010 Jan 12. PMID: 20066470; PMCID: PMC3076580.
In vitro protocol: 1. Bergman AM, Adema AD, Balzarini J, Bruheim S, Fichtner I, Noordhuis P, Fodstad O, Myhren F, Sandvold ML, Hendriks HR, Peters GJ. 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. doi: 10.1007/s10637-009-9377-7. Epub 2010 Jan 12. PMID: 20066470; PMCID: PMC3076580.
In vivo protocol: 1. Bergman AM, Adema AD, Balzarini J, Bruheim S, Fichtner I, Noordhuis P, Fodstad O, Myhren F, Sandvold ML, Hendriks HR, Peters GJ. 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. doi: 10.1007/s10637-009-9377-7. Epub 2010 Jan 12. PMID: 20066470; PMCID: PMC3076580.

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1: Poplin E, Wasan H, Rolfe L, Raponi M, Ikdahl T, Bondarenko I, Davidenko I, Bondar V, Garin A, Boeck S, Ormanns S, Heinemann V, Bassi C, Evans TR, Andersson R, Hahn H, Picozzi V, Dicker A, Mann E, Voong C, Kaur P, Isaacson J, Allen A. Randomized, Multicenter, Phase II Study of CO-101 Versus Gemcitabine in Patients With Metastatic Pancreatic Ductal Adenocarcinoma: Including a Prospective Evaluation of the Role of hENT1 in Gemcitabine or CO-101 Sensitivity. J Clin Oncol. 2013 Dec 10;31(35):4453-61. doi: 10.1200/JCO.2013.51.0826. Epub 2013 Nov 12. PubMed PMID: 24220555.

2: Stuurman FE, Lolkema MP, Huitema AD, Soetekouw PM, Rosing H, Rolfe L, Kaur P, Beijnen JH, van Tinteren H, Voest EE, Schellens JH. A phase 1 comparative pharmacokinetic and cardiac safety study of two intravenous formulations of CO-101 in patients with advanced solid tumors. J Clin Pharmacol. 2013 Aug;53(8):878-83. doi: 10.1002/jcph.108. Epub 2013 Jun 18. PubMed PMID: 23775853.

3: Stuurman FE, Voest EE, Awada A, Witteveen PO, Bergeland T, Hals PA, Rasch W, Schellens JH, Hendlisz A. Phase I study of oral CP-4126, a gemcitabine derivative, in patients with advanced solid tumors. Invest New Drugs. 2013 Aug;31(4):959-66. doi: 10.1007/s10637-013-9925-z. Epub 2013 Jan 24. PubMed PMID: 23345000.

4: Adema AD, Smid K, Losekoot N, Honeywell RJ, Verheul HM, Myhren F, Sandvold ML, Peters GJ. Metabolism and accumulation of the lipophilic deoxynucleoside analogs elacytarabine and CP-4126. Invest New Drugs. 2012 Oct;30(5):1908-16. doi: 10.1007/s10637-011-9756-8. Epub 2011 Oct 15. PubMed PMID: 22002019; PubMed Central PMCID: PMC3432794.

5: Sandvold ML, Galmarini C, Myhren F, Peters G. The activity of the lipophilic nucleoside derivatives elacytarabine and CP-4126 in a panel of tumor cell lines resistant to nucleoside analogues. Nucleosides Nucleotides Nucleic Acids. 2010 Jun;29(4-6):386-93. doi: 10.1080/15257771003729625. PubMed PMID: 20544524.

6: Bergman AM, Adema AD, Balzarini J, Bruheim S, Fichtner I, Noordhuis P, Fodstad O, Myhren F, Sandvold ML, Hendriks HR, Peters GJ. 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. doi: 10.1007/s10637-009-9377-7. Epub 2010 Jan 12. PubMed PMID: 20066470; PubMed Central PMCID: PMC3076580.

7: Adema AD, Laan AC, Myhren F, Fichtner I, Verheul HM, Sandvold ML, Peters GJ. 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. PubMed PMID: 19956857.

8: Galmarini CM, Myhren F, Sandvold ML. CP-4055 and CP-4126 are active in ara-C and gemcitabine-resistant lymphoma cell lines. Br J Haematol. 2009 Jan;144(2):273-5. doi: 10.1111/j.1365-2141.2008.07467.x. Epub 2008 Nov 19. PubMed PMID: 19036103.