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Purity: ≥98%
Beta-Lapachone (also known as ARQ-501; NSC 26326; ARQ501; NSC-26326) is a novel, naturally occurring, potent and selective DNA topoisomerase I inhibitor with potential antineoplastic activity. It shows no inhibitory effects on either DNA ligase or DNA topoisomerase II. The bark of Tabebuia sp. yields a naphthoquinone compound called beta-lapachone, which has antitumor, antibacterial, antifungal, and antitrypanosomal properties. Through indirect mechanisms involving the induction of p53-independent apoptosis and cell cycle arrest, mediated by changes in the activities of cell cycle control regulatory proteins, betalachone demonstrates its anti-tumor effects.
| Targets |
Topoisomerase I
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
DNA topoisomerase I is cultured in 20 μL of relaxation buffer (50 mM Tris, pH 7.5) with or without drugs (including β-Lapachone). (30 μg/mL bovine serum albumin, 50 mM KCl, 10 mM MgCl2, 0.5 mM dithiothreitol, 0.5 mM EDTA) for 30 minutes at 37°C. Proteinase K (50 μg/mL) and 1% SDS are added to halt reactions. The products are separated by electrophoresis in 1% agarose gel in TAE buffer (0.04 M tris acetate, 0.001 M EDTA) following an additional 1-hour incubation at 37°C. After electrophoresis, ethidium bromide is used to stain the gel. Utilizing an NIH image analysis system, the photographic negative is scanned.
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| Cell Assay |
The MTT assay is used to quantify cytotoxicity. Two days before different concentrations of either topotecan or β-lapachone are added, IMR-32 and JCI cells are plated in 96-well microtiter plates at a concentration of 5.0 × 104 (topotecan) or 2.5 × 104 (β-lapachone) cells/well/100 µL medium. After that, the cells are kept in a CO2 incubator at 37°C for 72 hours. A Cell Proliferation Kit I is used to measure the proliferation of cells. Four distinct cultures are used in the experiments.
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| Animal Protocol |
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| Additional Infomation |
Beta-lapachone is a benzochromenone that is 3,4-dihydro-2H-benzo[h]chromene-5,6-dione substituted by geminal methyl groups at position 2. Isolated from Tabebuia avellanedae, it exhibits antineoplastic and anti-inflammatory activities. It has a role as an antineoplastic agent, an anti-inflammatory agent and a plant metabolite. It is a benzochromenone and a member of orthoquinones.
Lapachone has been used in trials studying the treatment of Cancer, Carcinoma, Advanced Solid Tumors, Head and Neck Neoplasms, and Carcinoma, Squamous Cell. beta-Lapachone has been reported in Catalpa longissima, Handroanthus guayacan, and other organisms with data available. Lapachone is a poorly soluble, ortho-naphthoquinone with potential antineoplastic and radiosensitizing activity. Beta-lapachone (b-lap) is bioactivated by NAD(P)H:quinone oxidoreductase-1 (NQO1), creating a futile oxidoreduction that generates high levels of superoxide. In turn, the highly reactive oxygen species (ROS) interact with DNA, thereby causing single-strand DNA breaks and calcium release from endoplasmic reticulum (ER) stores. Eventually, the extensive DNA damage causes hyperactivation of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme facilitating DNA repair, accompanied by rapid depletion of NAD+/ATP nucleotide levels. As a result, a caspase-independent and ER-stress induced mu-calpain-mediated cell death occurs in NQO1-overexpressing tumor cells. NQO1, a flavoprotein and two-electron oxidoreductase, is overexpressed in a variety of tumors. |
| Molecular Formula |
C15H14O3
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| Molecular Weight |
242.27
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| Exact Mass |
242.094
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| Elemental Analysis |
C, 74.36; H, 5.82; O, 19.81
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| CAS # |
4707-32-8
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| Related CAS # |
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| PubChem CID |
3885
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| Appearance |
Brown to red solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
381.4±42.0 °C at 760 mmHg
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| Melting Point |
>110ºC (dec.)
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| Flash Point |
169.7±27.9 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.595
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| LogP |
2.82
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
18
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| Complexity |
445
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C2C3=C([H])C([H])=C([H])C([H])=C3C(C(C=2C([H])([H])C([H])([H])C1(C([H])([H])[H])C([H])([H])[H])=O)=O
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| InChi Key |
QZPQTZZNNJUOLS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H14O3/c1-15(2)8-7-11-13(17)12(16)9-5-3-4-6-10(9)14(11)18-15/h3-6H,7-8H2,1-2H3
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| Chemical Name |
2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.32 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (10.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.86 mg/mL (11.81 mM) in 20% SBE-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1276 mL | 20.6381 mL | 41.2763 mL | |
| 5 mM | 0.8255 mL | 4.1276 mL | 8.2553 mL | |
| 10 mM | 0.4128 mL | 2.0638 mL | 4.1276 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00622063 | Completed | Drug: ARQ 501 | Cancer | ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) |
December 2006 | Phase 1 Phase 2 |
| NCT00075933 | Completed | Drug: ARQ 501 | Cancer | ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) |
September 2003 | Phase 1 |
| NCT00524524 | Completed | Drug: ARQ 501 | Advanced Solid Tumors | ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) |
August 2007 | Phase 1 |
| NCT00099190 | Completed | Drug: ARQ 501 | Amyotrophic Lateral Sclerosis | ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) |
December 2004 | Phase 1 |
| NCT00310518 | Completed | Drug: ARQ 501 | Cancer | ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA) |
February 2006 | Phase 2 |
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