WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 204970
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.
MedKoo Cat#: 204970
Name: Gemcitabine elaidate
Chemical Formula: C27H43F2N3O5
Exact Mass: 527.31708
Molecular Weight: 527.644
Elemental Analysis: C, 61.46; H, 8.21; F, 7.20; N, 7.96; O, 15.16
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
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
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.