DHA-paclitaxel

WARNING: This product is for research use only, not for human or veterinary use.

Description:DHA-paclitaxel, also know as Taxoprexin, is prodrug comprised of the naturally occurring omega-3 fatty acid docosahexaenoic acid (DHA) covalently conjugated to the anti-microtubule agent paclitaxel. Because tumor cells take up DHA, DHA-paclitaxel is delivered directly to tumor tissue, where the paclitaxel moiety binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. Paclitaxel also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). DHA-paclitaxel exhibits improved pharmacokinetic and toxicity profiles when compared to conventional paclitaxel and has demonstrated antineoplastic activity in animal models of cancer.

Price and Availability

DHA-paclitaxel is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 206077Name: DHA-paclitaxelCAS#: 199796-52-6Chemical Formula: C69H81NO15Exact Mass: 1163.56062Molecular Weight: 1164.38Elemental Analysis: C, 71.17; H, 7.01; N, 1.20; O, 20.61

Synonym:DHA-paclitaxel; DHA-Taxol; DHA-Tax; Docosahexaenoic Acid-Paclitaxel conjugate; US brand name: Taxoprexin.

IUPAC/Chemical Name:(2aR,4S,4aS,6R,9S,11S,12S,12bS)-9-(((2R,3S)-3-benzamido-2-((4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoyloxy)-3-phenylpropanoyl)oxy)-12-(benzoyloxy)-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b-diyl diacetate.

InChi Key:LRCZQSDQZJBHAF-PUBGEWHCSA-N

InChi Code:InChI=1S/C69H81NO15/c1-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22-23-24-25-35-42-55(74)83-59(57(49-36-29-26-30-37-49)70-63(76)50-38-31-27-32-39-50)65(78)82-52-44-69(79)62(84-64(77)51-40-33-28-34-41-51)60-67(7,53(73)43-54-68(60,45-80-54)85-48(4)72)61(75)58(81-47(3)71)56(46(52)2)66(69,5)6/h9-10,12-13,15-16,18-19,21-22,24-34,36-41,52-54,57-60,62,73,79H,8,11,14,17,20,23,35,42-45H2,1-7H3,(H,70,76)/b10-9-,13-12-,16-15-,19-18-,22-21-,25-24-/t52-,53-,54+,57-,58+,59+,60-,62-,67+,68-,69+/m0/s1

SMILES Code:O=C1[C@H](OC(C)=O)C(C2(C)C)=C(C)[C@@H](OC([C@@H]([C@H](C3=CC=CC=C3)NC(C4=CC=CC=C4)=O)OC(CC/C=CC/C=CC/C=CC/C=CC/C=CC/C=CCC)=O)=O)C[C@@]2(O)[C@@H](OC(C5=CC=CC=C5)=O)[C@@]6([H])[C@@]1(C)[C@@H](O)C[C@@H]7[C@@]6(OC(C)=O)CO7

Technical Data

Additional Information

DHA-paclitaxel (or Taxoprexin) is an investigational drug (from Protarga Inc) made by linking paclitaxel to docosahexaenoic acid (DHA), a fatty acid that is easily taken up by tumor cells; the DHA-paclitaxel “appears not to be cytotoxic until the bond with DHA is cleaved within the cell.” The advantage of DHA-paclitaxel over paclitaxel is DHA-paclitaxelÂ’s ability to carry much higher concentrations of paclitaxel to the cells, which are maintained for longer periods in the tumor cells, thus increasing their action. With increased activity, DHA-paclitaxel, also known as Taxoprexin, may have a more successful response in cancer patients than Taxol, and it may be able to treat more types of cancer than Taxol has been able to treat. In 2007, a phase II clinical trial reported "modest activity in patients with oesophago-gastric cancer".  (source: http://en.wikipedia.org/wiki/DHA-paclitaxel).      

References

1: Homsi J, Bedikian AY, Papadopoulos NE, Kim KB, HwuWJ, Mahoney SL, Hwu P. Phase 2 open-label study of weeklydocosahexaenoic acid-paclitaxel in patients with metastatic uvealmelanoma. Melanoma Res. 2010 Dec;20(6):507-10. doi:10.1097/CMR.0b013e3283403ce9. PubMed PMID: 20881508.

2: Bedikian AY, DeConti RC, Conry R, Agarwala S, Papadopoulos N, Kim KB,Ernstoff M. Phase 3 study of docosahexaenoic acid-paclitaxel versusdacarbazine in patients with metastatic malignant melanoma. Ann Oncol.2011 Apr;22(4):787-93. doi: 10.1093/annonc/mdq438. Epub 2010 Sep 20.PubMed PMID: 20855467.

3: Homsi J, Bedikian AY, Kim KB, Papadopoulos NE, Hwu WJ, Mahoney SL,Hwu P. Phase 2 open-label study of weekly docosahexaenoic acid-paclitaxelin cutaneous and mucosal metastatic melanoma patients. Melanoma Res.2009 Aug;19(4):238-42. doi: 10.1097/CMR.0b013e32832a1e2f. PubMed PMID:19521262.

4: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find ExpClin Pharmacol. 2008 May;30(4):313-31. PubMed PMID: 18773127.

5: Fracasso PM, Picus J, Wildi JD, Goodner SA, Creekmore AN, Gao F,Govindan R, Ellis MJ, Tan BR, Linette GP, Fu CJ, Pentikis HS, ZumbrunSC, Egorin MJ, Bellet RE. Phase 1 and pharmacokinetic study of weeklydocosahexaenoic acid-paclitaxel, Taxoprexin, in resistant solid tumormalignancies. Cancer Chemother Pharmacol. 2009 Feb;63(3):451-8. doi:10.1007/s00280-008-0756-0. Epub 2008 Apr 15. PubMed PMID: 18414864.

6: Jones RJ, Hawkins RE, Eatock MM, Ferry DR, Eskens FA, Wilke H, EvansTR. A phase II open-label study of DHA-paclitaxel (Taxoprexin) by 2-hintravenous infusion in previously untreated patients with locallyadvanced or metastatic gastric or oesophageal adenocarcinoma. CancerChemother Pharmacol. 2008 Mar;61(3):435-41. Epub 2007 Apr 18. PubMedPMID: 17440725.

7: Payne M, Ellis P, Dunlop D, Ranson M, Danson S, Schacter L, Talbot D.DHA-paclitaxel (Taxoprexin) as first-line treatment in patients withstage IIIB or IV non-small cell lung cancer: report of a phase IIopen-label multicenter trial. J Thorac Oncol. 2006 Nov;1(9):984-90.PubMed PMID: 17409983.

8: Harries M, O"Donnell A, Scurr M, Reade S, Cole C, Judson I, GreystokeA, Twelves C, Kaye S. Phase I/II study of DHA-paclitaxel in combinationwith carboplatin in patients with advanced malignant solid tumours. Br JCancer. 2004 Nov 1;91(9):1651-5. PubMed PMID: 15494716; PubMed CentralPMCID: PMC2410023.

9: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. MethodsFind Exp Clin Pharmacol. 2004 Apr;26(3):211-44. PubMed PMID: 15148527.

10: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. MethodsFind Exp Clin Pharmacol. 2004 Mar;26(2):129-61. PubMed PMID: 15071612.