lurbinectedin   Click here for help

GtoPdb Ligand ID: 10681

Synonyms: PM 01183 | PM-01183 | PM01183 | Zepzelca®
Approved drug
lurbinectedin is an approved drug (FDA (2020))
Compound class: Synthetic organic
Comment: Lurbinectedin (PM01183) is an investigational anti-tumour agent [3] with potential activity against a wide range of tumours. Structurally it is a synthetic tetrahydroisoquinoline that is related to the marine ecteinascidins (e.g. trabectedin). Like trabectedin, lurbinectedin binds to the minor groove of DNA. Stable lurbinectedin-DNA adducts induce DNA double- and single-strand breaks which cause cell cycle arrest and ultimately, apoptotic cell death.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 4
Rotatable bonds 4
Topological polar surface area 189.58
Molecular weight 784.28
XLogP 3.64
No. Lipinski's rules broken 0
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Canonical SMILES COc1ccc2c(c1)c1CCN[C@@]3(c1[nH]2)CS[C@@H]1c2c(OC(=O)C)c(C)c4c(c2[C@H](COC3=O)N2[C@@H]1[C@@H]1N([C@H]([C@@H]2O)Cc2c1c(O)c(c(c2)C)OC)C)OCO4
Isomeric SMILES COc1ccc2c(c1)c1CCN[C@@]3(c1[nH]2)CS[C@@H]1c2c(OC(=O)C)c(C)c4c(c2[C@H](COC3=O)N2[C@@H]1[C@@H]1N([C@H]([C@@H]2O)Cc2c1c(O)c(c(c2)C)OC)C)OCO4
InChI InChI=1S/C41H44N4O10S/c1-17-11-20-12-25-39(48)45-26-14-52-40(49)41(38-22(9-10-42-41)23-13-21(50-5)7-8-24(23)43-38)15-56-37(31(45)30(44(25)4)27(20)32(47)33(17)51-6)29-28(26)36-35(53-16-54-36)18(2)34(29)55-19(3)46/h7-8,11,13,25-26,30-31,37,39,42-43,47-48H,9-10,12,14-16H2,1-6H3/t25-,26-,30+,31+,37+,39-,41+/m0/s1
No information available.
Summary of Clinical Use Click here for help
First-in-human results of lurbinectedin in patients with advanced solid tumours were reported in 2014 [1], and since then it has progressed to Phase 3 evaluations. Click here to link to's full list of lurbinectedin/PM01183 studies.
In the EU lurbinectedin has orphan drug authorisation for ovarian cancer (granted in 2012) and small cell lung cancer (SCLC, 2019).
A new drug application (NDA) was submitted to the FDA in late 2019, and accelerated approval/priority review for use as a second-line therapy in patients with SCLC who have progressed after prior platinum-containing therapy was authorised in February 2020. This converted to full FDA approval for this SCLC indication in June 2020.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02421588 Clinical Trial of Lurbinectedin (PM01183) in Platinum Resistant Ovarian Cancer Patients Phase 3 Interventional PharmaMar
NCT00877474 Phase I, Multicenter, Open-label, Dose-escalating, Clinical and Pharmacokinetic Study of PM01183 in Patients With Advanced Solid Tumors Phase 1 Interventional PharmaMar 1
NCT02566993 Clinical Trial of Lurbinectedin (PM01183)/Doxorubicin (DOX) Versus Cyclophosphamide (CTX), Doxorubicin (DOX) and Vincristine (VCR) (CAV) or Topotecan as Treatment in Patients With Small-Cell Lung Cancer Phase 3 Interventional PharmaMar 2