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1mg |
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5mg |
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Lurbinectedin (PM01183; PM-01183; Zepzelca) is a covalent DNA minor groove binder with potent anticancer activity. It acts by covalently binding to residues lying in the minor groove of DNA, leading to delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death. Lurbinectedin has been approved in2020 for the treatment of adults with metastatic small cell lung cancer.
ln Vitro |
PM01183 is a newly developed synthetic alkaloid tetrahydroisoquinoline that is used to treat solid tumors. PM01183: Double-strand breaks in living cells are caused by DNA adducts, which lead to the accumulation of S-phase and subsequent cell disinfection. With an average GI50 value of 2.7 nM, PM01183's strong cytotoxic activity was found in a panel of 23 cell lines [2]. In vitro, lurbinectedin significantly inhibits human ovarian clear cell carcinoma (CCC) cells that are both chemically sensitive and robust[1].
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ln Vivo |
Lurbinectedin effectively suppressed tumor growth in CCC cell xenografts. There is a notable synergistic effect between SN-38 and luerbinectedin [1]. PM01183 markedly suppressed tumor growth in a four-cell xenograft model of human cancer, while lurbinectedin or NSC 119875 combination therapy effectively cured NSC 119875-sensitive and NSC 119875-combined single preclinical ovarian carcinoma tumors in animals. The combined treatment showed the greatest positive results, particularly for NSC 119875. inside tumors. Reduced proliferation, increased aberrant mitotic rates in malignancies, and triggered apoptosis are linked to luerbinectedin growth inhibition [3].
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References |
[1]. Takahashi R, et al. 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.
[2]. Leal JF, et al. PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity. Br J Pharmacol. 2010 Nov;161(5):1099-110. [3]. Vidal A, et al. Lurbinectedin (PM01183), a new DNA minor groove binder, inhibits growth of orthotopic primary graft of NSC 119875-resistant epithelial ovarian cancer. Clin Cancer Res. 2012 Oct 1;18(19):5399-411 |
Molecular Formula |
C41H44N4O10S
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Molecular Weight |
784.88
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Exact Mass |
784.2778
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Elemental Analysis |
C, 62.74; H, 5.65; N, 7.14; O, 20.38; S, 4.08
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CAS # |
497871-47-3
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Related CAS # |
Lurbinectedin-d3
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Appearance |
Solid powder
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SMILES |
S1C[C@@]2(C3=C(C4C=C(C=CC=4N3)OC)CCN2)C(=O)OC[C@@]2([H])C3=C4C(=C(C)C(=C3[C@]1([H])[C@@]1([H])[C@@]3([H])C5C(=C(C(C)=CC=5C[C@@]([H])([C@@H](N12)O)N3C)OC)O)OC(C)=O)OCO4
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Synonyms |
PM-01183 PM01183 Lurbinectedin
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO : ~20 mg/mL (~25.48 mM)
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.2741 mL | 6.3704 mL | 12.7408 mL | |
5 mM | 0.2548 mL | 1.2741 mL | 2.5482 mL | |
10 mM | 0.1274 mL | 0.6370 mL | 1.2741 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.