Lurbinectedin | CAS# 497871-47-3 | DNA groove-binding agent

MedKoo Cat#: 581065 | Name: Lurbinectedin

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Lurbinectedin, also known as PM01183, is a DNA minor groove-binding agent. PM01183 covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death. lurbinectedin inhibits the active transcription of the encoding genes. This has two consequences. It promotes tumor cell death and normalizes the tumor microenvironment.

Chemical Structure

Lurbinectedin

CAS#497871-47-3

Theoretical Analysis

MedKoo Cat#: 581065

Name: Lurbinectedin

CAS#: 497871-47-3

Chemical Formula: C41H44N4O10S

Exact Mass: 784.2778

Molecular Weight: 784.88

Elemental Analysis: C, 62.74; H, 5.65; N, 7.14; O, 20.38; S, 4.08

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.

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Related CAS #

497871-47-3

Synonym

Lurbinectedin; PM01183; PM-01183; PM 01183;

IUPAC/Chemical Name

(1'R,6R,6aR,7R,13S,14S,16R)-5-(Acetyloxy)-2',3',4',6,6a,7,9'-decahydro-8,14-dihydroxy-6',9-dimethoxy-4,10,23-trimethyl-spiro(6,16-(epithiopropaneoxymethano)-7.13-imino-12H-1,3-dioxolo[7,8]soquino[3,2-b][3]benzazocine-20,1'-[1H]pyrido[3,4-b]indol]-19-one

InChi Key

YDDMIZRDDREKEP-HWTBNCOESA-N

InChi Code

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

SMILES Code

Cc1cc2c(c(c1OC)O)[C@@H]3[C@@H]4[C@H]5c6c(c7c(c(c6OC(=O)C)C)OCO7)[C@@H](N4[C@H]([C@H](C2)N3C)O)COC(=O)[C@@]8(CS5)c9c(c1cc(ccc1[nH]9)OC)CCN8

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Lurbinectedin, also known as PM01183, is a synthetic tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one alkaloid analogue with potential antineoplastic activity. DNA minor groove-binding agent PM01183 covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death. Lurbinectedin is a marine-derived covalent DNA binder, approved in 2020.

Instruction

View handling instruction

Biological target:

Lurbinectedin inhibits RMG1 (IC50 = 1.25nM) and RMG2 (IC50 = 1.16nM)

In vitro activity:

We used human and patient-derived xenograft (PDX)-derived SCLC cell lines to evaluate the effect of lurbinectedin in vitro. We also demonstrate the antitumor effect of lurbinectedin in multiple de novo and transformed SCLC PDX models. Reference: Chakraborty S, Coleman C, Manoj P, Demircioglu D, Shah N, de Stanchina E, Rudin CM, Hasson D, Sen T. De Novo and Histologically Transformed Small-Cell Lung Cancer Is Sensitive to Lurbinectedin Treatment Through the Modulation of EMT and NOTCH Signaling Pathways. Clin Cancer Res. 2023 Sep 1;29(17):3526-3540. doi: 10.1158/1078-0432.CCR-23-0471. PMID: 37382635; PMCID: PMC10901109.

In vivo activity:

Additionally, lurbinectedin (Lur) and Teri potently and synergistically inhibited spheroid growth and depleted uridine and DRP1 phosphorylation in mouse tumors. Our results suggest combinations of Carbo and Lur with Teri or Leflu are efficacious and underscore how the relationship between DRP1/DHODH and mitochondrial plasticity serves as a potential therapeutic target to validate these treatment strategies in SCLC clinical trials. Reference: Mirzapoiazova T, Tseng L, Mambetsariev B, Li H, Lou CH, Pozhitkov A, Ramisetty SK, Nam S, Mambetsariev I, Armstrong B, Malhotra J, Arvanitis L, Nasser MW, Batra SK, Rosen ST, Wheeler DL, Singhal SS, Kulkarni P, Salgia R. Teriflunomide/leflunomide synergize with chemotherapeutics by decreasing mitochondrial fragmentation via DRP1 in SCLC. iScience. 2024 May 27;27(6):110132. doi: 10.1016/j.isci.2024.110132. PMID: 38993482; PMCID: PMC11237869.

	Solvent	mg/mL	mM
Solubility
	DMSO	20.0	25.48

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 784.88 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1: Chakraborty S, Coleman C, Manoj P, Demircioglu D, Shah N, de Stanchina E, Rudin CM, Hasson D, Sen T. De Novo and Histologically Transformed Small-Cell Lung Cancer Is Sensitive to Lurbinectedin Treatment Through the Modulation of EMT and NOTCH Signaling Pathways. Clin Cancer Res. 2023 Sep 1;29(17):3526-3540. doi: 10.1158/1078-0432.CCR-23-0471. PMID: 37382635; PMCID: PMC10901109. 2: Gadducci A, Cosio S. Trabectedin and lurbinectedin: Mechanisms of action, clinical impact, and future perspectives in uterine and soft tissue sarcoma, ovarian carcinoma, and endometrial carcinoma. Front Oncol. 2022 Nov 3;12:914342. doi: 10.3389/fonc.2022.914342. PMID: 36408147; PMCID: PMC9671549.

In vivo protocol:

1: Mirzapoiazova T, Tseng L, Mambetsariev B, Li H, Lou CH, Pozhitkov A, Ramisetty SK, Nam S, Mambetsariev I, Armstrong B, Malhotra J, Arvanitis L, Nasser MW, Batra SK, Rosen ST, Wheeler DL, Singhal SS, Kulkarni P, Salgia R. Teriflunomide/leflunomide synergize with chemotherapeutics by decreasing mitochondrial fragmentation via DRP1 in SCLC. iScience. 2024 May 27;27(6):110132. doi: 10.1016/j.isci.2024.110132. PMID: 38993482; PMCID: PMC11237869. 2: Gadducci A, Cosio S. Trabectedin and lurbinectedin: Mechanisms of action, clinical impact, and future perspectives in uterine and soft tissue sarcoma, ovarian carcinoma, and endometrial carcinoma. Front Oncol. 2022 Nov 3;12:914342. doi: 10.3389/fonc.2022.914342. PMID: 36408147; PMCID: PMC9671549.

1: Calvo E, Moreno V, Flynn M, Holgado E, Olmedo ME, Lopez Criado MP, Kahatt C, Lopez-Vilariño JA, Siguero M, Fernandez-Teruel C, Cullell-Young M, Soto Matos-Pita A, Forster M. Antitumor activity of lurbinectedin (PM01183) and doxorubicin in relapsed small-cell lung cancer: results from a phase I study. Ann Oncol. 2017 Oct 1;28(10):2559-2566. doi: 10.1093/annonc/mdx357. PubMed PMID: 28961837. 2: Erba E, Romano M, Gobbi M, Zucchetti M, Ferrari M, Matteo C, Panini N, Colmegna B, Caratti G, Porcu L, Fruscio R, Perlangeli MV, Mezzanzanica D, Lorusso D, Raspagliesi F, D'Incalci M. Ascites interferes with the activity of lurbinectedin and trabectedin: Potential role of their binding to alpha 1-acid glycoprotein. Biochem Pharmacol. 2017 Nov 15;144:52-62. doi: 10.1016/j.bcp.2017.08.001. Epub 2017 Aug 4. PubMed PMID: 28782526. 3: Belgiovine C, Bello E, Liguori M, Craparotta I, Mannarino L, Paracchini L, Beltrame L, Marchini S, Galmarini CM, Mantovani A, Frapolli R, Allavena P, D'Incalci M. Lurbinectedin reduces tumour-associated macrophages and the inflammatory tumour microenvironment in preclinical models. Br J Cancer. 2017 Aug 22;117(5):628-638. doi: 10.1038/bjc.2017.205. Epub 2017 Jul 6. PubMed PMID: 28683469; PubMed Central PMCID: PMC5572168. 4: Jimeno A, Sharma MR, Szyldergemajn S, Gore L, Geary D, Diamond JR, Fernandez Teruel C, Soto Matos-Pita A, Iglesias JL, Cullell-Young M, Ratain MJ. Phase I study of lurbinectedin, a synthetic tetrahydroisoquinoline that inhibits activated transcription, induces DNA single- and double-strand breaks, on a weekly × 2 every-3-week schedule. Invest New Drugs. 2017 Aug;35(4):471-477. doi: 10.1007/s10637-017-0427-2. Epub 2017 Jan 20. PubMed PMID: 28105566. 5: Paz-Ares L, Forster M, Boni V, Szyldergemajn S, Corral J, Turnbull S, Cubillo A, Teruel CF, Calderero IL, Siguero M, Bohan P, Calvo E. Phase I clinical and pharmacokinetic study of PM01183 (a tetrahydroisoquinoline, Lurbinectedin) in combination with gemcitabine in patients with advanced solid tumors. Invest New Drugs. 2017 Apr;35(2):198-206. doi: 10.1007/s10637-016-0410-3. Epub 2016 Nov 21. PubMed PMID: 27873130. 6: Harlow ML, Maloney N, Roland J, Guillen Navarro MJ, Easton MK, Kitchen-Goosen SM, Boguslawski EA, Madaj ZB, Johnson BK, Bowman MJ, D'Incalci M, Winn ME, Turner L, Hostetter G, Galmarini CM, Aviles PM, Grohar PJ. Lurbinectedin Inactivates the Ewing Sarcoma Oncoprotein EWS-FLI1 by Redistributing It within the Nucleus. Cancer Res. 2016 Nov 15;76(22):6657-6668. doi: 10.1158/0008-5472.CAN-16-0568. Epub 2016 Oct 3. PubMed PMID: 27697767; PubMed Central PMCID: PMC5567825. 7: Céspedes MV, Guillén MJ, López-Casas PP, Sarno F, Gallardo A, Álamo P, Cuevas C, Hidalgo M, Galmarini CM, Allavena P, Avilés P, Mangues R. Lurbinectedin induces depletion of tumor-associated macrophages, an essential component of its in vivo synergism with gemcitabine, in pancreatic adenocarcinoma mouse models. Dis Model Mech. 2016 Dec 1;9(12):1461-1471. Epub 2016 Oct 20. PubMed PMID: 27780828; PubMed Central PMCID: PMC5200894. 8: Santamaría Nuñez G, Robles CM, Giraudon C, Martínez-Leal JF, Compe E, Coin F, Aviles P, Galmarini CM, Egly JM. Lurbinectedin Specifically Triggers the Degradation of Phosphorylated RNA Polymerase II and the Formation of DNA Breaks in Cancer Cells. Mol Cancer Ther. 2016 Oct;15(10):2399-2412. Epub 2016 Sep 14. PubMed PMID: 27630271. 9: Metaxas Y, Cathomas R, Mark M, von Moos R. Combination of cisplatin and lurbinectedin as palliative chemotherapy in progressive malignant pleural mesothelioma: Report of two cases. Lung Cancer. 2016 Dec;102:136-138. doi: 10.1016/j.lungcan.2016.07.012. Epub 2016 Jul 14. PubMed PMID: 27440191. 10: Lima M, Bouzid H, Soares DG, Selle F, Morel C, Galmarini CM, Henriques JA, Larsen AK, Escargueil AE. Dual inhibition of ATR and ATM potentiates the activity of trabectedin and lurbinectedin by perturbing the DNA damage response and homologous recombination repair. Oncotarget. 2016 May 3;7(18):25885-901. doi: 10.18632/oncotarget.8292. PubMed PMID: 27029031; PubMed Central PMCID: PMC5041952. 11: Takahashi R, Mabuchi S, Kawano M, Sasano T, Matsumoto Y, Kuroda H, Kozasa K, Hashimoto K, Sawada K, Kimura T. Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary. PLoS One. 2016 Mar 17;11(3):e0151050. doi: 10.1371/journal.pone.0151050. eCollection 2016. PubMed PMID: 26986199; PubMed Central PMCID: PMC4795692. 12: Pernice T, Bishop AG, Guillen MJ, Cuevas C, Aviles P. Development of a liquid chromatography/tandem mass spectrometry assay for the quantification of PM01183 (lurbinectedin), a novel antineoplastic agent, in mouse, rat, dog, Cynomolgus monkey and mini-pig plasma. J Pharm Biomed Anal. 2016 May 10;123:37-41. doi: 10.1016/j.jpba.2016.01.043. Epub 2016 Jan 21. PubMed PMID: 26871278. 13: Elez ME, Tabernero J, Geary D, Macarulla T, Kang SP, Kahatt C, Pita AS, Teruel CF, Siguero M, Cullell-Young M, Szyldergemajn S, Ratain MJ. First-in-human phase I study of Lurbinectedin (PM01183) in patients with advanced solid tumors. Clin Cancer Res. 2014 Apr 15;20(8):2205-14. doi: 10.1158/1078-0432.CCR-13-1880. Epub 2014 Feb 21. PubMed PMID: 24563480. 14: Romano M, Frapolli R, Zangarini M, Bello E, Porcu L, Galmarini CM, García-Fernández LF, Cuevas C, Allavena P, Erba E, D'Incalci M. Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104). Int J Cancer. 2013 Nov;133(9):2024-33. doi: 10.1002/ijc.28213. Epub 2013 May 25. PubMed PMID: 23588839. 15: Vidal A, Muñoz C, Guillén MJ, Moretó J, Puertas S, Martínez-Iniesta M, Figueras A, Padullés L, García-Rodriguez FJ, Berdiel-Acer M, Pujana MA, Salazar R, Gil-Martin M, Martí L, Ponce J, Molleví DG, Capella G, Condom E, Viñals F, Huertas D, Cuevas C, Esteller M, Avilés P, Villanueva A. Lurbinectedin (PM01183), a new DNA minor groove binder, inhibits growth of orthotopic primary graft of cisplatin-resistant epithelial ovarian cancer. Clin Cancer Res. 2012 Oct 1;18(19):5399-411. doi: 10.1158/1078-0432.CCR-12-1513. Epub 2012 Aug 15. PubMed PMID: 22896654.