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Revision as of 13:47, 10 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 468593418 of page Trabectedin for the Chem/Drugbox validation project (updated: 'ChEMBL', 'KEGG', 'StdInChI', 'StdInChIKey', 'CAS_number').  Latest revision as of 02:27, 10 December 2024 edit Citation bot (talk | contribs)Bots5,419,524 edits Add: pmc, bibcode. | Use this bot. Report bugs. | Suggested by Dominic3203 | Linked from User:Marbletan/sandbox | #UCB_webform_linked 983/2664 
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{{short description|Chemical compound}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox {{Drugbox
| Verifiedfields = changed
| IUPAC_name = (1<nowiki>'</nowiki>''R'',6''R'',6a''R'',7''R'',13''S'',14''S'',16''R'')-6',8,14-trihydroxy-7',9-dimethoxy-4,10,23-trimethyl-19-oxo-3',4',6,7,12,13,14,16-octahydrospiroisoquinobenzazocine-20,1'(2'''H'')-isoquinolin]-5-yl acetate
| Watchedfields = changed
| image = Trabectedin .png
| verifiedrevid = 470612054
| image = Trabectedin structure.svg
| alt =


<!--Clinical data--> <!-- Clinical data -->
| pronounce = {{IPAc-en|t|r|ə|ˈ|b|ɛ|k|t|ɪ|d|ɪ|n}}<br />{{respell|trə|BEK|ti|din}}
| tradename =
| tradename = Yondelis
| Drugs.com = {{drugs.com|international|trabectedin}}
| Drugs.com = {{drugs.com|monograph|trabectedin}}
| licence_EU = Yondelis
| MedlinePlus = a615059
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| licence_EU = yes
| pregnancy_US = <!-- A / B / C / D / X -->
| DailyMedID = Trabectedin
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->
| pregnancy_AU = D
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| pregnancy_AU_comment = <ref name="Yondelis APM summary" />
| legal_UK = POM
| pregnancy_category =
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| dependency_liability =
| legal_status =
| addiction_liability =
| routes_of_administration = ] | routes_of_administration = ]
| ATC_prefix = L01
| ATC_suffix = CX01
| ATC_supplemental =


<!--Pharmacokinetic data--> <!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref name="Yondelis APM summary">{{cite web | title=Yondelis | website=Therapeutic Goods Administration (TGA) | date=3 May 2021 | url=https://www.tga.gov.au/apm-summary/yondelis | access-date=6 September 2021}}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Yondelis 1 mg powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC) | website=(emc) | date=21 September 2020 | url=https://www.medicines.org.uk/emc/product/11123/smpc | access-date=30 September 2020}}</ref>
| legal_US = Rx-only
| legal_US_comment = <ref name="Yondelis FDA label" />
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Yondelis EPAR" />
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = Rx-only

<!-- Pharmacokinetic data -->
| bioavailability = Not applicable (IV only) | bioavailability = Not applicable (IV only)
| protein_bound = 94 to 98% | protein_bound = 94 to 98%
| metabolism = ] (mostly ]-mediated) | metabolism = ] (mostly ]-mediated)
| metabolites =
| onset =
| elimination_half-life = 180 hours (mean) | elimination_half-life = 180 hours (mean)
| duration_of_action =
| excretion = Mostly fecal | excretion = Mostly fecal


<!--Identifiers--> <!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = <!-- blanked - oldvalue: 114899-77-3 -->
| CAS_number = 114899-77-3
| ATC_prefix = L01
| CAS_supplemental =
| ATC_suffix = CX01
| PubChem = 108150 | PubChem = 108150
| IUPHAR_ligand = 2774
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB05109 | DrugBank = DB05109
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 16736970
| ChemSpiderID = 97236
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = ID0YZQ2TCP | UNII = ID0YZQ2TCP
| KEGG_Ref = {{keggcite|changed|kegg}}
| ChEMBL = <!-- blanked - oldvalue: 297812 -->
| KEGG = <!-- blanked - oldvalue: D06199 --> | KEGG =D06199
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 84050
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 297812
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = ecteinascidin 743, ET-743

<!-- Chemical and physical data -->
| IUPAC_name = (1<nowiki>'</nowiki>''R'',6''R'',6a''R'',7''R'',13''S'',14''S'',16''R'')-6',8,14-trihydroxy-7',9-dimethoxy-4,10,23-trimethyl-19-oxo-3',4',6,7,12,13,14,16-octahydrospiroisoquinobenzazocine-20,1'(2'''H'')-isoquinolin]-5-yl acetate
| C=39 | H=43 | N=3 | O=11 | S=1 | C=39 | H=43 | N=3 | O=11 | S=1
| SMILES = Cc1cc2c(c(c1OC)O)345c6c(c7c(c(c6OC(=O)C)C)OCO7)(N4((C2)N3C)O)COC(=O)8(CS5)c9cc(c(cc9CCN8)O)OC
| molecular_weight = 761.84 g/mol
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| smiles = CC(=O)Oc1c5c(c2OCOc2c1C)6COC(=O)4(NCCc3cc(O)c(OC)cc34)CCS59N6(O)8Cc7cc(C)c(OC)c(O)c79N8C
| InChI = 1S/C40H45N3O11S/c1-17-11-21-12-23-38(47)43-24-15-51-39(48)40(22-14-26(49-5)25(45)13-20(22)7-9-41-40)8-10-55-37(31(43)30(42(23)4)27(21)32(46)33(17)50-6)29-28(24)36-35(52-16-53-36)18(2)34(29)54-19(3)44/h11,13-14,23-24,30-31,37-38,41,45-47H,7-10,12,15-16H2,1-6H3/t23-,24-,30+,31+,37+,38-,40+/m0/s1 | StdInChI = 1S/C39H43N3O11S/c1-16-9-20-10-22-37(46)42-23-13-50-38(47)39(21-12-25(48-5)24(44)11-19(21)7-8-40-39)14-54-36(30(42)29(41(22)4)26(20)31(45)32(16)49-6)28-27(23)35-34(51-15-52-35)17(2)33(28)53-18(3)43/h9,11-12,22-23,29-30,36-37,40,44-46H,7-8,10,13-15H2,1-6H3/t22-,23-,29+,30+,36+,37-,39+/m0/s1
| StdInChI_comment =
| InChIKey = AXYPHJWOKPNXAX-IZQXKXCFSA-N
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C40H45N3O11S/c1-17-11-21-12-23-38(47)43-24-15-51-39(48)40(22-14-26(49-5)25(45)13-20(22)7-9-41-40)8-10-55-37(31(43)30(42(23)4)27(21)32(46)33(17)50-6)29-28(24)36-35(52-16-53-36)18(2)34(29)54-19(3)44/h11,13-14,23-24,30-31,37-38,41,45-47H,7-10,12,15-16H2,1-6H3/t23-,24-,30+,31+,37+,38-,40+/m0/s1
| StdInChIKey = AXYPHJWOKPNXAX-IZQXKXCFSA-N | StdInChIKey = PKVRCIRHQMSYJX-AIFWHQITSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}

'''Trabectedin''', sold under the brand name '''Yondelis''', is an antitumor chemotherapy medication for the treatment of advanced ] and ].<ref name="Yondelis FDA label">{{cite web | title=Yondelis- trabectedin injection, powder, lyophilized, for solution | website=DailyMed | date=22 September 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=472bd78e-be17-4b9d-90f4-9482c3aec9ff | access-date=30 September 2020}}</ref><ref name="Yondelis EPAR">{{cite web | title=Yondelis EPAR | website=] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/yondelis | access-date=30 September 2020}}</ref>

The most common adverse reactions include nausea, fatigue, vomiting, constipation, decreased appetite, diarrhea, peripheral edema, dyspnea, and headache.<ref name="Yondelis FDA label" /><ref name="Yondelis EPAR" />

It is sold by Pharma Mar S.A. and Johnson and Johnson. It is approved for use in the European Union, Russia, South Korea and the United States. The European Commission and the U.S. ] (FDA) granted ] status to trabectedin for soft-tissue sarcomas and ].

==Discovery and production==
During the 1950s and 1960s, the ] carried out a wide-ranging program of screening plant and marine organism material. As part of that program, extract from the ] '']'' was found to have anticancer activity in 1969.<ref>{{cite journal| vauthors = Lichter W, Wallham LL, Van Der Worf BA, Middle Brook RE, Sigal MM, Weinheimer AJ | title = Food Drugs from the Sea | journal = Proceedings | date = August 1972 | veditors = Worthen LW |publisher= Marine Tech Soc | volume=173 |pages=117–127 }}</ref>
Separation and characterization of the active molecules had to wait many years for the development of sufficiently sensitive techniques, and the structure of one of them, Ecteinascidin 743, was determined by KL Rinehart at the University of Illinois in 1984.<ref name="pmid10608919">{{cite journal | vauthors = Rinehart KL | title = Antitumor compounds from tunicates | journal = Medicinal Research Reviews | volume = 20 | issue = 1 | pages = 1–27 | date = January 2000 | pmid = 10608919 | doi = 10.1002/(SICI)1098-1128(200001)20:1<1::AID-MED1>3.0.CO;2-A | s2cid = 25117225 }}</ref> Rinehart had collected his sea squirts by scuba diving in the reefs of the West Indies.<ref name="harvard">{{cite web | vauthors = Cromie WJ | date = 4 May 2000 | work = Harvard University Gazette |url=http://news.harvard.edu/gazette/2000/05.04/cancersquirt.html | archive-url = https://web.archive.org/web/20060603174004/http://news.harvard.edu/gazette/2000/05.04/cancersquirt.html | archive-date = 3 June 2006 |title=Potent cancer drugs made -- Sea squirts provide recipe }}</ref> The biosynthetic pathway responsible for producing the drug has been determined to come from ''Candidatus'' Endoecteinascidia frumentensis, a microbial symbiont of the tunicate.<ref name="pmid21875091">{{cite journal | vauthors = Rath CM, Janto B, Earl J, Ahmed A, Hu FZ, Hiller L, Dahlgren M, Kreft R, Yu F, Wolff JJ, Kweon HK, Christiansen MA, Håkansson K, Williams RM, Ehrlich GD, Sherman DH | title = Meta-omic characterization of the marine invertebrate microbial consortium that produces the chemotherapeutic natural product ET-743 | journal = ACS Chemical Biology | volume = 6 | issue = 11 | pages = 1244–1256 | date = November 2011 | pmid = 21875091 | pmc = 3220770 | doi = 10.1021/cb200244t }}</ref>
The Spanish company ] licensed the compound from the University of Illinois before 1994{{Citation needed|date=July 2008}} and attempted to farm the sea squirt with limited success.<ref name="harvard"/> Yields from the sea squirt are extremely low as around 1,000 kilograms of animals is needed to isolate 1&nbsp;gram of trabectedin - and about 5&nbsp;grams were believed to be needed for a clinical trial<ref name="newscientist">{{cite web | vauthors = Pain S | date = 14 September 1996 | title = Hostages of the deep - Prospectors are taking to the seas in search of new and promising chemicals. But the better the drugs turn out to be, the greater the threat to the animals that produce them. |url=https://www.newscientist.com/article/mg15120473.600-hostages-of-the-deep--prospectors-are-taking-to-the-seas-in-search-of-new-and-promising-chemicalsbut-the-better-the-drugs-turn-out-to-be-the-greater-the-threat-to-the-animalsthat-produce-them-itstephanie-painit-investigates.html | work = New Scientist }}</ref> so Rinehart asked the Harvard chemist ] to search for a synthetic method of preparation. His group developed such a method and published it in 1996.<ref name=corey>{{cite journal | journal=Journal of the American Chemical Society |volume=118 |issue=38 |year=1996 |pages=9202–9203 |title=Enantioselective Total Synthesis of Ecteinascidin 743 | vauthors = Corey EJ, Gin DY, Kania RS |doi=10.1021/ja962480t |bibcode=1996JAChS.118.9202C }}</ref> This was later followed by a simpler and more tractable method which was patented by Harvard and subsequently licensed to PharmaMar.<ref name="harvard"/> The current{{when|date=October 2020}} supply is based on a semisynthetic process developed by PharmaMar starting from safracin B, a chemical obtained by fermentation of the bacterium '']''.<ref>{{cite journal | vauthors = Cuevas C, Pérez M, Martín MJ, Chicharro JL, Fernández-Rivas C, Flores M, Francesch A, Gallego P, Zarzuelo M, de La Calle F, García J, Polanco C, Rodríguez I, Manzanares I | title = Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from cyanosafracin B | journal = Organic Letters | volume = 2 | issue = 16 | pages = 2545–2548 | date = August 2000 | pmid = 10956543 | doi = 10.1021/ol0062502 }}</ref> PharmaMar entered into an agreement with Johnson & Johnson to market the compound outside Europe.{{Citation needed|date=July 2008}}

==Approvals and indications==
Trabectedin was first trialed in humans in 1996.{{Citation needed|date=July 2008}}

===Soft tissue sarcoma===
In 2007, the European Commission gave authorization for the marketing of trabectedin, under the trade name Yondelis, "for the treatment of patients with advanced soft tissue sarcoma, after failure of ]s and ], or who are unsuited to receive these agents".<ref>{{cite web |title= YONDELIS (trabectedin) | work = Post-Authorization Summary of Positive Opinion | date = 24 September 2009 |url=https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summary-positive-opinion-yondelis-24-september-2009_en.pdf |publisher=European Medicines Agency |access-date=12 November 2019}}</ref><ref name="Yondelis EPAR" /> The European Medicine Agency's evaluating committee, the ] (CHMP), observed that trabectedin had not been evaluated in an adequately designed and analyzed randomized controlled trial against current best care, and that the clinical efficacy data were mainly based on patients with ] and ]. However, the pivotal study did show a significant difference between two different trabectedin treatment regimens, and due to the rarity of the disease, the CHMP considered that marketing authorization could be granted under exceptional circumstances.<ref>{{cite web |title=CHMP evaluation |url=http://www.emea.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000773/WC500045833.pdf }}</ref> As part of the approval PharmaMar agreed to conduct a further trial to identify whether any specific chromosomal ] could be used to predict responsiveness to trabectedin.<ref>{{cite web |url=http://www.pharmamar.com/en/press/news_release.cfm?newsReleaseID=179&year=2008 |archive-url=https://web.archive.org/web/20080918003629/http://www.pharmamar.com/en/press/news_release.cfm?newsReleaseID=179&year=2008 |url-status=dead |archive-date=September 18, 2008 |title=PharmaMar website }}</ref>

Trabectedin is also approved in South Korea<ref>{{cite news | title=S.Korea approves Zeltia cancer drug Yondelis | website=Reuters | date=8 May 2008 | url=https://www.reuters.com/article/zeltia-korea-idUSB73735320080508 | access-date=30 September 2020}}</ref> and Russia.{{cn|date=October 2020}}

In 2015, (after a phase III study comparing trabectedin with ]<ref name=DAC2015>{{cite web | url = http://www.cancernetwork.com/sarcoma/trabectedin-superior-dacarbazine-leiomyosarcoma-liposarcoma | archive-url = https://web.archive.org/web/20160305031632/http://www.cancernetwork.com/sarcoma/trabectedin-superior-dacarbazine-leiomyosarcoma-liposarcoma | archive-date = 5 March 2016 | title = Trabectedin Superior to Dacarbazine for Leiomyosarcoma, Liposarcoma | work = Cancer Network | date = 21 September 2015 }}</ref>), the ] approved trabectedin (Yondelis) for the treatment of liposarcoma and leiomyosarcoma that is either unresectable or has metastasized. Patients must have received prior chemotherapy with an anthracycline.<ref name=FDA2015>{{cite web | url = http://www.cancernetwork.com/sarcoma/fda-approves-trabectedin-yondelis-advanced-soft-tissue-sarcoma | archive-url = https://web.archive.org/web/20160317173946/http://www.cancernetwork.com/sarcoma/fda-approves-trabectedin-yondelis-advanced-soft-tissue-sarcoma/ | archive-date = 17 March 2016 | title = FDA Approves Trabectedin (Yondelis) for Advanced Soft-Tissue Sarcoma | work = Cancer Network | date = 26 October 2015 }}</ref>

===Ovarian cancer and other===
In 2008, the submission was announced of a registration dossier to the ] and the FDA for Yondelis when administered in combination with ] (Doxil, Caelyx) for the treatment of women with relapsed ]. In 2011, Johnson & Johnson voluntarily withdrew the submission in the United States following a request by the FDA for an additional phase III study to be done in support of the submission.<ref>{{cite news |title=J&J pulls submission for Zeltia's Yondelis | vauthors = Grogan K |url=http://www.pharmatimes.com/Article/11-05-03/J_J_pulls_submission_for_Zeltia_s_Yondelis.aspx |newspaper=] |location=London, England |date=3 May 2011 |at=Online PharmaTimes |access-date=7 May 2011 |archive-url=https://web.archive.org/web/20111002180803/http://www.pharmatimes.com/Article/11-05-03/J_J_pulls_submission_for_Zeltia_s_Yondelis.aspx |url-status=live |archive-date=2 October 2011 }}</ref>

Trabectedin is{{when|date=October 2015}} also in phase II trials for prostate, breast, and paediatric cancers.<ref>{{cite web |url=http://www.pharmamar.com/contenidos.aspx?menu=66 | archive-url = https://web.archive.org/web/20120213191543/http://www.pharmamar.com/contenidos.aspx?menu=66 | archive-date = 13 February 2012 | title = Yondelis (trabectedin) | work = PharmaMar }}</ref>

== Structure ==
Trabectedin is composed of three ] ], eight rings including one 10-membered heterocyclic ring containing a ] residue, and seven chiral centers.<ref>{{cite journal | vauthors = D'Incalci M, Galmarini CM | title = A review of trabectedin (ET-743): a unique mechanism of action | journal = Molecular Cancer Therapeutics | volume = 9 | issue = 8 | pages = 2157–2163 | date = August 2010 | pmid = 20647340 | doi = 10.1158/1535-7163.MCT-10-0263 | s2cid = 6723817 }}</ref><ref name="pmid32586501">{{cite book | vauthors = Chukwueke UN, Wen PY | title = Meningiomas, Part II | chapter = Medical management of meningiomas | series = Handbook of Clinical Neurology | volume = 170 | pages = 291–302 | date = 2020 | pmid = 32586501 | pmc = 6169485 | doi = 10.1016/B978-0-12-822198-3.00048-3 | veditors = McDermott MW |publisher=Elsevier | isbn=978-0-12-822198-3 }}</ref>

==Biosynthesis==
]

The biosynthesis of trabectedin in the tunicate ] ''Candidatus'' ''Endoecteinascidia frumentensis'' starts with a fatty acid loading onto the acyl-ligase domain of the EtuA3 module. A cysteine and glycine are then loaded as canonical NRPS amino acids. A tyrosine residue is modified by the enzymes EtuH, EtuM1, and EtuM2 to add a hydroxyl at the meta position of the phenol, and adding two methyl groups at the para-hydroxyl and the meta carbon position. This modified tyrosine reacts with the original substrate via a ], where the amine group is converted to an imine by deprotonation, then attacks the free aldehyde to form a carbocation that is quenched by electrons from the methyl-phenol ring. This is done in the EtuA2 T-domain. This reaction is done a second time to yield a dimer of modified tyrosine residues that have been further cyclized via Pictet-Spengler reaction, yielding a bicyclic ring moiety. The EtuO and EtuF3 enzymes continue to post-translationally modify the molecule, adding several functional groups and making a sulfide bridge between the original cysteine residue and the beta-carbon of the first tyrosine to form ET-583, ET-597, ET-596, and ET-594 which have been previously isolated.<ref name="pmid21875091"/> A third ''O''-methylated tyrosine is added and cyclized via Pictet-Spengler to yield the final product.<ref name="pmid21875091"/>

==Total synthesis==
The ] by E.J. Corey <ref name=corey /> used this proposed biosynthesis to guide their synthetic strategy. The synthesis uses such reactions as the ], ], the ], and ] ]-based ]-] ] ]. A separate synthetic process also involved the ] to assist in the formation of the pentacyclic core. This reaction was unprecedented for using such a one pot multicomponent reaction in the synthesis of such a complex molecule.

== Mechanism of action ==
Recently,{{when|date=October 2020}} it has been shown that trabectedin blocks DNA binding of the oncogenic ] ] and reverses the transcriptional program in ]. By reversing the genetic program created by this transcription factor, trabectedin promotes differentiation and reverses the oncogenic phenotype in these cells.<ref name=Grohar2011/>

Other than transcriptional interference, the mechanism of action of trabectedin is complex and not completely understood. The compound is known to bind and alkylate DNA at the N2 position of guanine. It is known from ''in vitro'' work that this binding occurs in the minor groove, spans approximately three to five base pairs and is most efficient with CGG sequences. Additional favorable binding sequences are TGG, AGC, or GGC. Once bound, this reversible covalent adduct bends DNA toward the major groove, interferes directly with activated transcription, poisons the ] complex, promotes degradation of RNA polymerase II, and generates DNA double-strand breaks.<ref name=Grohar2011>{{cite journal | vauthors = Grohar PJ, Griffin LB, Yeung C, Chen QR, Pommier Y, Khanna C, Khan J, Helman LJ | title = Ecteinascidin 743 interferes with the activity of EWS-FLI1 in Ewing sarcoma cells | journal = Neoplasia | volume = 13 | issue = 2 | pages = 145–153 | date = February 2011 | pmid = 21403840 | pmc = 3033593 | doi = 10.1593/neo.101202 }} and works cited therein.</ref>

In 2024, researchers from ] and ] determined that abortive ] of trabectedin-DNA adducts forms persistent single-strand breaks (SSBs) as the adducts block the second of the two sequential ] incisions. The researchers mapped the 3’-hydroxyl groups of SSBs originating from the first ] incision at trabectedin lesions, recording TC-NER on a genome-wide scale, which resulted in a TC-NER-profiling assay TRABI-Seq.<ref>{{cite journal | vauthors = Son K, Takhaveev V, Mor V, Yu H, Dillier E, Zilio N, Püllen NJ, Ivanov D, Ulrich HD, Sturla SJ, Schärer OD | title = Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes | journal = Nature Communications | volume = 15 | issue = 1 | pages = 1388 | date = February 2024 | pmid = 38360910 | doi = 10.1038/s41467-024-45664-7 | pmc = 10869700 | bibcode = 2024NatCo..15.1388S | hdl = 20.500.11850/661709 | hdl-access = free }}</ref>

== Society and culture ==
=== Legal status ===
In September 2020, the European Medicines Agency recommended that the use of trabectedin in treating ovarian cancer remain unchanged.<ref>{{cite web | title=Yondelis | website=] (EMA) | date=27 February 2020 | url=https://www.ema.europa.eu/en/medicines/human/referrals/yondelis | access-date=30 September 2020}}</ref>

== References ==
{{reflist}}

{{Chemotherapeutic agents}}
{{Portal bar | Medicine}}

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