# Vintafolide
> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Vintafolide
> Markdown URL: https://mediated.wiki/source/Vintafolide.md
> Source: https://en.wikipedia.org/wiki/Vintafolide
> Source revision: 1329897720
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)
{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name =''N''-(4-{[(2-Amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}benzoyl)-L-γ-glutamyl-L-α-aspartyl-L-arginyl-L-α-aspartyl-L-α-aspartyl-L-cysteine disulfide with methyl (5''S'',7''R'',9''S'')-5-ethyl-9-[(3a''R'',4''R'',5''S'',5a''R'',10b''R'',13a''R'')-3a-ethyl-4,5-dihydroxy-8-methoxy-6-methyl-5-({2-[(2-sulfanylethoxy)carbonyl]hydrazinyl}carbonyl)-3a,4,5,5a,6,11,12,13a-octahydro-1''H''-indolizino[8,1-''cd'']carbazol-9-yl]-5-hydroxy-1,4,5,6,7,8,9,10-octahydro-2''H''-3,7-methanoazacycloundecino[5,4-''b'']indol-9-carboxylate
| synonyms = EC-145
| image = Vintafolide.svg
| image_class = skin-invert-image
| width = 250px
| alt = Vintafolide structure
| image2 =
| width2 =
| Drugs.com =
| MedlinePlus =
| pregnancy_category =
| legal_status = IND
| routes_of_administration =
| bioavailability =
| metabolism =
| elimination_half-life =
| excretion =
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 742092-03-1
| ATC_prefix = L01
| ATC_suffix = CA06
| PubChem =
| IUPHAR_ligand =
| DrugBank_Ref =
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 27444385
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 36O410ZD4I
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D10434
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI =
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL =
| C=86 | H=109 | N=21 | O=26 | S=2
| smiles = [H]/N=C(\N)/NCCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CSSCCOC(=O)NNC(=O)[C@@]1([C@H]2[C@]3(CCN4[C@H]3[C@]([C@H]1O)(C=CC4)CC)c5cc(c(cc5N2C)OC)[C@]6(C[C@@H]7C[C@](CN(C7)CCc8c6[nH]c9c8cccc9)(CC)O)C(=O)OC)O)C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CC[C@@H](C(=O)O)NC(=O)c1ccc(cc1)NCc1cnc2c(n1)c(=O)[nH]c(n2)N
| StdInChI = 1S/C86H109N21O26S2/c1-6-82(129)35-42-36-85(78(127)132-5,64-47(21-26-106(39-42)41-82)46-12-8-9-13-50(46)95-64)49-30-48-57(34-58(49)131-4)105(3)75-84(48)23-27-107-25-11-22-83(7-2,74(84)107)76(125)86(75,130)77(126)103-104-81(128)133-28-29-134-135-40-56(73(123)124)100-70(119)55(33-62(113)114)99-69(118)54(32-61(111)112)98-67(116)51(14-10-24-90-79(87)88)96-68(117)53(31-60(109)110)94-59(108)20-19-52(72(121)122)97-66(115)43-15-17-44(18-16-43)91-37-45-38-92-65-63(93-45)71(120)102-80(89)101-65/h8-9,11-13,15-18,22,30,34,38,42,51-56,74-76,91,95,125,129-130H,6-7,10,14,19-21,23-29,31-33,35-37,39-41H2,1-5H3,(H,94,108)(H,96,117)(H,97,115)(H,98,116)(H,99,118)(H,100,119)(H,103,126)(H,104,128)(H,109,110)(H,111,112)(H,113,114)(H,121,122)(H,123,124)(H4,87,88,90)(H3,89,92,101,102,120)/t42-,51-,52-,53-,54-,55-,56-,74-,75+,76+,82-,83+,84+,85-,86-/m0/s1
| StdInChI_Ref =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KUZYSQSABONDME-QRLOMCMNSA-N
}}
'''Vintafolide''' is an investigational targeted cancer therapeutic currently under development by [Endocyte](/source/Endocyte) and [Merck & Co.](/source/Merck_%26_Co.)[[http://www.ama-assn.org/resources/doc/usan/vintafolide.pdf Statement on a nonproprietary name adopted by the USAN Council], United States Adopted Names (USAN) Council, 6 April 2012]
Vintafolide is designed to deliver the toxic vinblastine drug selectively to cells expressing the [folate receptor](/source/folate_receptor) using [folate targeting](/source/folate_targeting).[{{cite journal | vauthors = Dosio F, Milla P, Cattel L | title = EC-145, a folate-targeted Vinca alkaloid conjugate for the potential treatment of folate receptor-expressing cancers | journal = Current Opinion in Investigational Drugs | volume = 11 | issue = 12 | pages = 1424–33 | date = December 2010 | pmid = 21154124 }}]
It is being developed with a companion imaging agent, [etarfolatide](/source/etarfolatide), that identifies patients that express the folate receptor and thus would likely respond to the treatment with vintafolide.[{{cite journal|last1=Kuo|first1=Phillip H. | name-list-style = vanc |title=Companion Imaging Diagnostics for Targeted Therapies|journal=Radiology Today|date=February 2013|volume=14|issue=2|page=32|url=https://www.radiologytoday.net/archive/rt0213p12.shtml}}]
A Phase 3 study evaluating vintafolide for the treatment of [platinum-resistant ovarian cancer](/source/platinum-resistant_ovarian_cancer) (PROCEED trial) and a Phase 2b study(TARGET trial) in [non-small-cell lung carcinoma](/source/non-small-cell_lung_carcinoma) (NSCLC) are ongoing (in 2012).[{{cite web|title=Merck, Endocyte in Development Deal|url=http://www.dddmag.com/news/2012/04/merck-endocyte-development-deal|website=Drug Development & Discovery magazine|date=2012-04-25}}]
A [Marketing Authorization Application](/source/Marketing_Authorization_Application) (MAA) filing for vintafolide and etarfolatide for the treatment of patients with [folate receptor](/source/folate_receptor)-positive platinum-resistant [ovarian cancer](/source/ovarian_cancer) in combination with [doxorubicin](/source/doxorubicin), pegylated liposomal doxorubicin (PLD), has been accepted by the [European Medicines Agency](/source/European_Medicines_Agency).[{{cite news|title=EMA Accepts For Review MAA Filings For Vintafolide And Etarfolatide|url=https://www.rttnews.com/2012700/ema-accepts-for-review-maa-filings-for-vintafolide-and-etarfolatide.aspx|publisher=rttnews.com|date=2012-11-27}}] The drug received [orphan drug status](/source/orphan_drug_status) in Europe in March 2012.[{{cite news | url = https://www.reuters.com/article/us-merck-idUSBRE83F0W120120416 | title = Endocyte soars on cancer drug deal with Merck | work = Reuters | date = Apr 16, 2012 | first=Balaji | last=Sridharan | name-list-style = vanc }}] [Merck & Co.](/source/Merck_%26_Co.) acquired the development and marketing rights to this experimental cancer drug from [Endocyte](/source/Endocyte) in April 2012.[{{cite news|last1=Garde|first1=Damian |name-list-style = vanc |title=Merck halts study of the billion-dollar cancer drug vintafolide|url=http://www.fiercebiotech.com/story/merck-halts-study-billion-dollar-cancer-drug-vintafolide/2014-05-02|access-date=21 April 2015|publisher=Fierce Biotech|date=2014-05-02}}][[http://www.fiercebiotech.com/press-releases/merck-and-endocyte-announce-independent-dsmb-recommends-vintafolide-proceed Merck and Endocyte Announce Independent DSMB Recommends Vintafolide PROCEED Phase 3 Trial Be Stopped for Futility Following Interim Analysis (undated)]]
== Mechanism of action ==
[Folate](/source/Folate) is required for cell division, and rapidly dividing [cancer cell](/source/cancer_cell)s often express [folate receptor](/source/folate_receptor)s in order to capture enough [folate](/source/folate) to support rapid cell growth. Elevated expression of the [folate receptor](/source/folate_receptor) occurs in many diseases, including other aggressively growing [cancer](/source/cancer)s and [inflammatory disorders](/source/inflammatory_disorders).[{{cite journal | vauthors = Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP | title = Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay | journal = Analytical Biochemistry | volume = 338 | issue = 2 | pages = 284–93 | date = March 2005 | pmid = 15745749 | doi = 10.1016/j.ab.2004.12.026 }}] Vintafolide binds to the [folate receptor](/source/folate_receptor) and is subsequently taken up by the cell through a natural internalization process called [endocytosis](/source/endocytosis). Once inside the cell, vintafolide’s linker releases the [chemotherapy](/source/chemotherapy) drug which kills the cell.