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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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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
InChI Key YDDMIZRDDREKEP-HWTBNCOESA-N
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 ClinicalTrials.gov'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