View source for Halichondrin B

{{Chembox
| ImageFile = Halichondrin B.svg
| ImageSize = 250px
| IUPACName = (1''S'',2''S'',2&prime;''S'',3''S'',3a''S'',3a&prime;''S'',5''R'',6''S'',7''S'',7&prime;''S'',7a''S'',7a&prime;''S'',9''S'',12''S'',14''R'',16''R'',18''S'',20''S'',22''R'',26''R'',28''S'',29''S'',30''R'',34''R'',37''S'',39''R'',40''S'',41''R'',43''R'',44''S'')-7,7&prime;,14&prime;&prime;,29&prime;&prime;-tetramethyl-8&prime;&prime;,15&prime;&prime;-dimethylidene-2-(1,3,4-trihydroxybutyl)decahydro-3&prime;''H'',32&prime;&prime;''H''-dispiro[furo[3,2-b]pyran-5,5&prime;-furo[3,2-b]pyran-2&prime;,24&prime;&prime;-[2,19,23,27,31,38,42,45,47,48,49]undecaoxaundecacyclo[32.9.2.1~3,40~.1~3,41~.1~6,9~.1~12,16
~.0~18,30~.0~20,28~.0~22,26~.0~37,44~.0~39,43~]nonatetracontan]-32&prime;&prime;-one
| IUPACName_hidden=yes
| OtherNames = 
| Section1 = {{Chembox Identifiers
|  CASNo = 
|  PubChem = 
|  ChemSpiderID = 10256208
|  SMILES = OCC(O)CC(O)[C@@H]1C[C@@H]2O[C@@]3(C[C@H](C)[C@@H]2O1)C[C@H](C)[C@@H]4O[C@]%10(C[C@@H]4O3)C[C@H]%11O[C@H]%12[C@H](C)[C@H]%13OC(=O)C[C@H]8CC[C@@H]9O[C@H]7[C@H]6O[C@]5(O[C@H]([C@@H]7O[C@@H]6C5)[C@H]9O8)C
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|  InChI = InChI=1S/C60H86O19/c1-26-13-33-7-9-37-27(2)14-35(65-37)11-12-58-23-46-54(78-58)55-56(72-46)57(79-58)53-38(69-55)10-8-34(67-53)16-48(64)73-52-31(6)51-43(68-42(52)17-39(66-33)30(26)5)19-41-45(71-51)22-60(74-41)24-47-50(77-60)29(4)21-59(76-47)20-28(3)49-44(75-59)18-40(70-49)36(63)15-32(62)25-61/h26,28-29,31-47,49-57,61-63H,2,5,7-25H2,1,3-4,6H3/t26-,28+,29+,31+,32?,33+,34-,35+,36?,37+,38+,39-,40+,41-,42+,43+,44+,45-,46-,47+,49+,50+,51+,52-,53+,54+,55+,56-,57+,58+,59-,60+/m1/s1
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| Section2 = {{Chembox Properties
|  C=60|H=86|O=19
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|  Density = 
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|  Solubility =
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| Section3 = {{Chembox Hazards
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}}

'''Halichondrin B''' is a naturally-occurring compound originally isolated from the marine sponge ''[[Halichondria]] okadai'' by Hirata and Uemura in 1986.<ref name="Hirata_1986">{{ cite journal | author = Hirata Y, Uemura D | title=Halichondrins - antitumor polyether macrolides from a marine sponge | journal=Pure Appl. Chem. | year = 1986 | volume = 58 | issue = 5 | pages = 701-710 | doi = 10.1351/pac198658050701}}</ref> In the same report, these authors also reported the exquisite [[anticancer]] activity of halichondrin B against murine cancer cells both in culture and in ''in vivo'' studies. Halichondrin B was highly prioritized for development as a novel [[anticancer]] therapeutic by the United States [[National Cancer Institute]] [http://www.dtp.nci.nih.gov/timeline/noflash/success_stories/S4_halichondrinB.htm] and, in 1991, was the original test case for identification of mechanism of action (in this case, [[tubulin]]-targeted [[mitotic inhibitor]]) by NCI's now famous but then-brand new "60-cell line screen"[http://www.dtp.nci.nih.gov/branches/btb/ivclsp.html].<ref name="pmid1874739">{{cite journal | author = Bai RL, Paull KD, Herald CL, Malspeis L, Pettit GR, Hamel E | title = Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data | journal = J. Biol. Chem. | volume = 266 | issue = 24 | pages = 15882–9 | year = 1991 | month = August | pmid = 1874739 | doi = | url = | issn = }}</ref>  The complete chemical synthesis of halichondrin B, a large (MW = 1,110) [[polyether]] [[macrolide]], was achieved by Yoshito Kishi and colleagues at [[Harvard University]] in 1992,<ref name="Aicher_1992">{{cite journal | author = Aicher TD, Buszek KR, Fang FG, Forsyth CJ, Jung SH, Kishi Y, Matelich MC, Scola PM, Spero DM, Yoon SK | title = Total synthesis of halichondrin B and norhalichondrin B | journal = J. Am. Chem. Soc. | year = 1992 | volume = 114 | issue = 8 | pages = 3162–3164 | doi = 10.1021/ja00034a086}}</ref>  an achievement that ultimately enabled the discovery and development of the structurally-simplified and pharmaceutically-optimized analog [[eribulin]] (E7389, ER-086526, NSC-707389).<ref name="pmid11221827">{{cite journal | author = Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, Welsh S, Zheng W, Seletsk BM, Palme MH, Habgood GJ, Singer LA, Dipietro LV, Wang Y, Chen JJ, Quincy DA, Davis A, Yoshimatsu K, Kishi Y, Yu MJ, Littlefield BA | title = In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B | journal = Cancer Res. | volume = 61 | issue = 3 | pages = 1013–21 | year = 2001 | month = February | pmid = 11221827 | doi = | url = | issn = }}</ref><ref name="isbn0-8493-1863-7">{{cite book | editor = Newman DJ, Kingston DGI, Cragg, GM | authorlink = | others = | title = Anticancer agents from natural products | edition = | language = | publisher = Taylor & Francis | location = Washington, DC | year = 2005 | chapter = Discovery of E7389, a fully synthetic macrocyclic ketone analogue of halichondrin B | author = Yu MJ, Kishi Y, Littlefield BA | quote = | isbn = 0-8493-1863-7 | oclc = | doi = | url = | accessdate = }}</ref> Eribulin is currently being investigated by [[Eisai Co.]] for the third-line treatment of advanced breast cancer in patients who have been previously treated with anthracyclines, taxanes and capecitabine, as well as a variety of other solid tumors, including non-small cell lung cancer, prostate cancer and sarcoma.<ref>"Drugs.com, Eisai Announces Change in U.S. Submission Schedule for E7389 New Drug Application". http://www.drugs.com/nda/e7389_080201.html. Retrieved on 2008-02-06.</ref>

==References==
{{reflist}}

[[Category:Drugs]]

[[da:Halichondrin_B]]
[[Category:2Fix]]