CT-179
Based on 1 Customer Validation
CT-179 is a brain-penetrant and orally active OLIG2 inhibitor with a human IC50 of 1250 nM. CT-179 disrupts OLIG2 dimerization, phosphorylation, and DNA binding, blocking OLIG2-driven transcription. CT-179 induces G2/M phase arrest and increases G0 population. CT-179 induces apoptosis by reducing anti-apoptotic proteins and increasing cleaved caspase-3 and cleaved PARP. CT-179 can be used for the research of subgroup medulloblastoma.
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- Pureza : 99.79%
- No. CAS: 1996636-69-1
- Fòrmula: C17H22Cl2N6O
- Peso molecular:397.30
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Almacenamiento:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
[1]|
Caspase-3 |
PARP |
In Vitro
CT-179 (10 nM-10 μM; 1 hour) dose-dependently disrupts OLIG2 dimerization in live HEK293 cells, with an IC50 of 1250 nM[1].
CT-179 (1-10 µM; 1 hour) reduces OLIG2-DNA binding in live HEK293 cells, as shown by increased diffusion of DNA-bound OLIG2 and reduced fractional DNA-bound OLIG2 at concentrations of 1 µM and 10 µM[1].
CT-179 (250 nM; 24 hours) blocks OLIG2-driven transcription in Daoy SHH-medulloblastoma cells, as measured by reduced activity of an LHX8 promoter luciferase reporter[1].
CT-179 (1 µM) shows minimal relevant off-target kinase inhibition in vitro; while it inhibits FLT3 with an IC50 of 20 nM in a cell-free assay, the predicted in vivo cell potency is too low to be biologically meaningful[1].
CT-179 (160 nM-2.5 µM) shows minimal off-target effects in normal human primary cells at biologically relevant concentrations (160 nM, 630 nM), with only limited proliferation reduction observed at the supraphysiological concentration of 2.5 µM[1].
CT-179 (1 nM-10 μM; 7 days) reduces viability in OLIG2-expressing SHH-medulloblastoma cell lines (Daoy, UW228, Med-813) in a manner correlating with OLIG2 expression, with IC50 values ranging from 143.6 nM to 965.2 nM, and shows no activity in OLIG2-negative cell lines[1].
CT-179 (1 µM; 17 h-7 days) induces apoptosis, G2/M phase arrest, and mitotic disruption in Daoy SHH-medulloblastoma cells, and potentiates radiotherapy-induced apoptosis[1].
CT-179 (1 µM; 17-96 hours) induces apoptosis and disrupts mitotic mechanisms in Med-813 SHH-medulloblastoma cells, and potentiates radiotherapy-induced apoptosis[1].
CT-179 (1 µM; 48 hours) induces cell death in patient-derived medulloblastoma explant organoids (including SHH-subgroup R902), and when combined with radiotherapy, further reduces proliferation without increasing stem cell populations[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Daoy SHH-medulloblastoma
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Concentration:1 µM
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Incubation Time:17 h; 24 h; 48 h; 72 h; 96 h; 7 days;
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Result:Induced apoptosis, shown by dose-dependent increases in cleaved caspase-3 (cC3) and cleaved PARP over time, and reduced levels of anti-apoptotic proteins MCL-1, BCL-2, and BCL-xL.
Sensitized Daoy cells to RT-induced apoptosis, with significantly higher apoptotic cell percentages in the combination group compared to single-agent treatments on day 1 and day 3.
Induced G2/M phase arrest, decreased cyclin B1, CDK1, and p-CDK1, and maintained elevated p-HH3, resulting in abnormal nuclear morphology (multinucleation, satellite micronuclei) and disrupted mitotic spindle formation.
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Cell Line:Med-813 SHH-medulloblastoma
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Concentration:1 µM
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Incubation Time:17 h; 24 h; 48 h; 72 h; 96 h
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Result:Induced apoptosis, with significantly higher apoptotic cell percentages in the CT-179 and combination groups compared to control on day 3.
Disrupted mitotic mechanisms, with an initial increase in cyclin B1, CDK1, and p-HH3 over 24 hours (accompanied by decreased p-CDK1), followed by decreases in cyclin B1 and CDK1 and a marked increase in p-CDK1 at later time points.
In Vivo
CT-179 (75 mg/kg; p.o.; every other day) as a single agent prolongs median event-free survival to 76 days, and combination with radiotherapy further extends median event-free survival to 100.5 days in SHH-subgroup medulloblastoma-bearing NRG mice[1].
CT-179 (80 mg/kg; i.p.; every other day) as a single agent reduces tumor proliferation, induces cell cycle arrest and neuronal differentiation, slows tumor growth, and improves event-free survival, while combination with radiotherapy further enhances event-free survival in SHH-subgroup medulloblastoma-bearing G-Smo mice[1].
CT-179 (80 mg/kg; i.p.; every other day) combined with POx-Palbo enhances cell cycle arrest, increases apoptosis, and improves event-free survival more effectively than either single agent in SHH-subgroup medulloblastoma-bearing G-Smo mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-Rag1null IL2rgnull (NRG) (female, 6-7 week-old, orthotopic cerebellar engraftment with Daoy-luci cells)[1]
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Dosage:50 mg/kg
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Administration:i.p.; twice weekly; two weeks
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Result:Increased median event-free survival (EFS) to 60 days (vs. 55 days for vehicle control).
Increased median EFS to 75.5 days when combined with radiotherapy, which was statistically significant compared to vehicle, CT-179 alone, and radiotherapy alone.
Significantly delayed tumor growth in the brain and spinal cord, with reduced luminescence signal compared to vehicle, CT-179 alone, and radiotherapy alone at day 42.
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Animal Model:NOD-Rag1null IL2rgnull (NRG) (female, 6-7 week-old, orthotopic cerebellar engraftment with Med-813-luci cells)[1]
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Dosage:75 mg/kg
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Administration:p.o.; every other day
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Result:Increased median EFS to 76 days (vs. 71 days for vehicle control).
Increased median EFS to 100.5 days when combined with radiotherapy, which was statistically significant compared to vehicle, CT-179 alone, and radiotherapy alone.
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Animal Model:Gfap-Cre/SmoM2 (G-Smo) (genetically engineered SHH-pathway hyperactivation inducing tumor formation by postnatal day 10)[1]
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Dosage:80 mg/kg
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Administration:i.p.; every other day
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Result:Showed a trend toward decreased phosphorylated OLIG2 (p-OLIG2; p=0.057) and significantly reduced phosphorylated RB (p-RB) in tumors after treatment from P10-P16.
Increased the G2/M fraction at 6 hours after a single dose, and by 24 hours, increased G0 and G2/M fractions with decreased G1 and mitotic (p-RB++) fractions.
Increased NEUN+ neuronal differentiation and OLIG2+/SOX10− tumor stem cell populations, while reducing tumor cross-sectional area at P17.
Significantly improved EFS compared to vehicle controls.
Resulted in statistically significant increased EFS when combined with radiotherapy compared to vehicle, CT-179 alone, and radiotherapy alone.
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Animal Model:Gfap-Cre/SmoM2 (G-Smo) (genetically engineered SHH-pathway hyperactivation inducing tumor formation by postnatal day 10)[1]
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Dosage:80 mg/kg plus 25 mg/kg POx-Palbo
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Administration:i.p.; every other day
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Result:Increased G0 cell fractions, increased G2/M cell fractions (with reduced mitotic p-RB++ cells, indicating G2 arrest), and increased cleaved caspase-3-positive apoptotic cells compared to vehicle, CT-179 alone, and POx-Palbo alone.
Resulted in improved event-free survival compared to either single agent.
Chemical Information
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No. CAS 1996636-69-1
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Appearance Solid
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Peso molecular 397.30
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Fòrmula C17H22Cl2N6O
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Color White to off-white
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SMILES
CC1=NC(NC(NC2=CC(Cl)=C(C=C2)Cl)=O)=NC(NCCCN(C)C)=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvente y solubilidad
In Vitro:
DMSO : 12.5 mg/mL (31.46 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1.25 mg/mL (3.15 mM); Clear solution
This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocolo
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Kinase activity and phosphorylation assays
Kinase activity assays measure the ability of kinases to transfer phosphate groups from ATP to specific substrates, while phosphorylation assays detect the presence and levels of phosphorylated proteins. Common methods include radiolabeled ATP incorporation (e. g. ,), ADP release detection via bioluminescence (e. g. ,[3]), enzyme-linked immunosorbent assays (ELISA) for phospho-specific epitopes (e. g. ,[6]), and microtiter-based formats for high-throughput screening (e. g. ,[8]). The ADP-Glo assay quantifies kinase activity by measuring ADP produced during phosphorylation using a luciferase-based system. Radiometric assays involve autoradiography or scintillation counting after incorporation of 32P-labeled ATP into substrate proteins. ELISA-based approaches rely on phospho-specific antibodies to detect activated kinases in cell lysates or purified samples.
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Protocol for Electrophoretic Mobility Shift Assay (EMSA)
Electrophoretic mobility shift assay detects protein-nucleic acid binding by incubating a labeled DNA or RNA probe with purified protein or cell extract, then separating free probe from slower-migrating protein-probe complexes on a native gel. For cancer cells, primary neurons, mouse tumor samples, intestinal organoids, inflammatory macrophages, or drug-treated samples, EMSA can measure transcription-factor DNA binding or RNA-binding protein activity in extracts, but it does not directly measure transcription, protein expression, or chromatin occupancy in intact cells. Specificity is judged by competition with unlabeled wild-type probe, failure of mutated or unrelated competitors to compete, and antibody supershift or disruption when the binding protein identity must be confirmed.
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Western Blot
Western blotting (WB) is a commonly used experimental method in molecular biology, biochemistry, and immunogenetics for identifying and quantifying target proteins. It combines gel electrophoresis with immunoassay, enabling researchers to analyze protein expression, post-translational modifications, and molecular weight.
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Detection of Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
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Protocol for Kinase activity and phosphorylation assays
Kinase activity assays measure transfer of phosphate from ATP to a protein or peptide substrate, generating phosphorylated substrate, ADP, or incorporated radiolabeled phosphate as the readout; phosphorylation assays measure site-specific phosphorylation in cells or tissues as a proxy for kinase-pathway activation, inhibition, or substrate regulation. Phosphorylation can be detected by phospho-specific Western blot, immunoprecipitation kinase assay, phospho-immunofluorescence, phospho-flow cytometry, luminescent ADP detection, radiolabeled ATP incorporation, or reporter-based pathway assays, and these readouts can be applied to cancer cells, primary neurons, mouse tumors, organoids, inflammatory macrophages, ferroptosis studies, and mitophagy studies when the kinase target is biologically relevant.
Pureza y Documentación
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Ficha de datos (280 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instrucciones de manejo (2659 KB)
Referencias
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.5170 mL | 12.5849 mL | 25.1699 mL | 62.9247 mL |
| 5 mM | 0.5034 mL | 2.5170 mL | 5.0340 mL | 12.5849 mL | |
| 10 mM | 0.2517 mL | 1.2585 mL | 2.5170 mL | 6.2925 mL | |
| 15 mM | 0.1678 mL | 0.8390 mL | 1.6780 mL | 4.1950 mL | |
| 20 mM | 0.1258 mL | 0.6292 mL | 1.2585 mL | 3.1462 mL | |
| 25 mM | 0.1007 mL | 0.5034 mL | 1.0068 mL | 2.5170 mL | |
| 30 mM | 0.0839 mL | 0.4195 mL | 0.8390 mL | 2.0975 mL |
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