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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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LDC195943 (also known as IMT1) is a novel, potent and highly specific inhibitor of POLRMT (human mitochondrial RNA polymerase) with anticancer activity.
ln Vitro |
In A2780, A549, and HeLa cells, IMT1 (0.00001-10 μM; 0-168 hours) dose-dependently lowers cell viability. About one-third of cancer cell lines, 89 cancer cell lines, and primary cells (human peripheral blood mononuclear cells (PBMC) and IMR90 lung fibroblasts) displayed a marked decline in cell viability as compared to the primary cells[1]. HeLa cells exhibit a dose-dependent reduction in mitochondrial transcript levels and a progressive depletion of mtDNA upon exposure to IMT1 (0.01-10 μM) for a duration of 24-200 hours. In a dose-dependent manner, the levels of subunits of respiratory chain complexes I, III, and IV (NDUFB8, UQCRC2, and COXI) drop [1]. A2780 cells' phosphorylated AMPK levels and the AMP/ATP ratio both significantly rise in response to a considerable time-dependent increase in mono- and diphosphate nucleotide levels, as revealed by IMT1 [1]. In A2780 cells expressing wild-type POLRMT, IMT1 significantly reduces mtDNA gene expression; in contrast, cells expressing mutant POLRMT (L796Q or L816Q) are resistant [1]. Both the biogenesis of the oxidative phosphorylation (OXPHOS) machinery and mtDNA transcription depend on POLRMT [1].
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Cell Assay |
Cell Viability Assay[1]
Cell Types: A2780, A549 and HeLa Cell Tested Concentrations: 0.00001-10 μM Incubation Duration: 0-168 hrs (hours) Experimental Results: There was a dose-dependent decrease in cell viability in A2780, A549 and HeLa cells, but not in human PBMC or pooled primary human hepatocytes were cytotoxic. |
References |
[1]. Nina A Bonekamp, et al. Small-molecule inhibitors of human mitochondrial DNA transcription. Nature. 2020 Dec;588(7839):712-716.
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Molecular Formula |
C21H21NO4
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Molecular Weight |
351.396
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CAS # |
2304621-31-4
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O(C1C=CC2=C(C=1)OC(C=C2C1C=CC=CC=1C)=O)C(C)C(N(C)C)=O
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Chemical Name |
Propanamide, N,N-dimethyl-2-[[4-(2-methylphenyl)-2-oxo-2H-1-benzopyran-7-yl]oxy]-
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Synonyms |
LDC 195943LDC-195943 LDC195943IMT1 IMT 1IMT-1
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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 : ~50 mg/mL (~142.29 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.11 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 (7.11 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 (7.11 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.8458 mL | 14.2288 mL | 28.4576 mL | |
5 mM | 0.5692 mL | 2.8458 mL | 5.6915 mL | |
10 mM | 0.2846 mL | 1.4229 mL | 2.8458 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.