Lurbinectedin
[CAS# 497871-47-3]

Identification

• Classification: API >> Inhibitor drug
• Name: Lurbinectedin
• Synonyms: PM 01183;PM 1183;Tryptamicidin;Zepsyre;Zepzelca;(1'R,6R,6aR,7R,13S,14S,16R)-5-(acetyloxy)-2',3',4',6,6a,7,9',13,14,16-decahydro-8,14-dihydroxy-6',9-dimethoxy-4,10,23-trimethyl-Spiro[6,16-(epithiopropanoxymethano)-7,13-imino-12H-1,3-dioxolo[7,8]isoquino[3,2-b][3]benzazocine-20,1'-[1H]pyrido[3,4-b]indol]-19-one (9CI)
• Molecular Formula: C₄₁H₄₄N₄O₁₀S
• Molecular Weight: 784.87
• CAS Registry Number: 497871-47-3
• EC Number: 881-505-0
• SMILES: CC1=CC2=C([C@@H]3[C@@H]4[C@H]5C6=C(C(=C7C(=C6[C@@H](N4[C@H]([C@H](C2)N3C)O)COC(=O)[C@@]8(CS5)C9=C(CCN8)C2=C(N9)C=CC(=C2)OC)OCO7)C)OC(=O)C)C(=C1OC)O

Properties

• Solubility: Sparingly Soluble (2.4E^-3 g/L) (25 °C), Calc.^*
• Density: 1.55±0.1 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2021 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07:GHS09 Warning
• Risk Statements: H302-H400-H410
• Safety Statements: P264-P270-P273-P301+P317-P330-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute toxicity	Acute Tox.	4	H302
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400

Discovery and Applications

Lurbinectedin, also known as PM01183, was discovered through a systematic screening process of chemical compounds derived from marine organisms. It was isolated from the Caribbean sea squirt, Ecteinascidia turbinata, by Spanish scientists. The discovery team was led by Dr. José Manuel Molina-Guijarro and Dr. Carlos María Galmarini from PharmaMar, a Spanish biopharmaceutical company. Lurbinectedin showed promising anti-cancer activity in preclinical studies, particularly against solid tumors.

Lurbinectedin has shown efficacy in treating various types of solid tumors, including small-cell lung cancer and ovarian cancer, by inhibiting RNA polymerase II. It disrupts transcription and DNA repair mechanisms in cancer cells, leading to their death. Lurbinectedin has been granted orphan drug designation by the FDA for the treatment of small-cell lung cancer and has received accelerated approval for metastatic small-cell lung cancer in combination with doxorubicin. Clinical trials are underway to explore its potential in treating other types of cancers.

References

2024. Lurbinectedin sensitizes PD-L1 blockade therapy by activating STING-IFN signaling in small-cell lung cancer. Cell reports. Medicine.
DOI: 10.1016/j.xcrm.2024.101852

2024. Efficacy and toxicity of lurbinectedin in subsequent systemic therapy of extensive-stage small cell lung cancer: a meta-analysis. BMC Cancer.
DOI: 10.1186/s12885-024-13104-w

2010. PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity. British Journal of Pharmacology.
DOI: 10.1111/j.1476-5381.2010.00945.x