ART558
Based on 50 publication(s) in Google Scholar
ART558 is a potent, selective and allosteric DNA polymerase theta (Polθ) inhibitor (IC50=7.9 nM). ART558 elicits BRCA-gene synthetic lethality and DNA damage. ART558 can be used for the research of cancer, such as breast cancer.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.75%
- No. CAS: 2603528-97-6
- Fòrmula: C21H21F3N4O2
- Peso molecular:418.41
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Almacenamiento:
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture and light)
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) ART558
More- Science. 2026 Feb 26;391(6788):eadz3121. [Abstract]
- Cell. 2025 Jun 26;188(13):3405-3421.e27. [Abstract]
- Nat Methods. 2023 Sep;20(9):1388-1399. [Abstract]
- Nat Cell Biol. 2024 May;26(5):770-783. [Abstract]
- Nat Commun. 2025 Dec 7. [Abstract]
- Nat Commun. 2025 Nov 3;16(1):9571. [Abstract]
- Nat Commun. 2025 Nov 26;16(1):10536. [Abstract]
- Nat Commun. 2025 Jul 15;16(1):6502. [Abstract]
- Nat Commun. 2025 May 12;16(1):4239. [Abstract]
- Nat Commun. 2024 Nov 6;15(1):9582. [Abstract]
- Nat Commun. 2024 Jul 11;15(1):5822. [Abstract]
- Nat Commun. 2024 Jun 21;15(1):5294. [Abstract]
- Nat Commun. 2023 Mar 13;14(1):1390. [Abstract]
- J Clin Invest. 2023 Jun 1;133(11):e165934. [Abstract]
- Nucleic Acids Res. 2026 Jan 5;54(1):gkaf1437. [Abstract]
- Nucleic Acids Res. 2024 Nov 21:gkae1069. [Abstract]
- Nucleic Acids Res. 2024 Dec 9:gkae1207. [Abstract]
- Cell Rep Med. 2026 Mar 17;7(3):102687. [Abstract]
- Proc Natl Acad Sci U S A. 2026 Mar 10;123(10):e2532479123. [Abstract]
- Genes Dev. 2024 Apr 17;38(5-6):213-232. [Abstract]
- J Transl Med. 2025 Oct 10;23(1):1079. [Abstract]
- Cell Rep. 2023 Apr 21;42(5):112428. [Abstract]
- Int J Mol Sci. 2024 Aug 23;25(17):9134. [Abstract]
- DNA Repair. 2025 Sep:153:103889. [Abstract]
- Surgery. 2024 Jun 18:S0039-6060(24)00303-9. [Abstract]
- Gene. 2023 Dec 20:888:147762. [Abstract]
- Pathologie (Heidelb). 2025 Nov 26. [Abstract]
- bioRxiv. 2026 Apr 9.
- bioRxiv. 2026 Feb 17.
- bioRxiv. 2026 Feb 21.
- bioRxiv. 2026 Jan 23:2026.01.22.701150. [Abstract]
- bioRxiv. 2025 Nov 30.
- bioRxiv. 2025 Nov 20.
- bioRxiv. 2025 Nov 21:2025.11.20.689563. [Abstract]
- bioRxiv. 2025 Sep 11.
- bioRxiv. 2025 Sep 21.
- Patent. US20250236892A1.
- bioRxiv. 2025 Jun 9:2025.06.09.658719. [Abstract]
- bioRxiv. 2025 May 10:2025.05.06.651696. [Abstract]
- Technische Universitat Darmstadt. 2025 May 8.
- bioRxiv. 2025 January 24.
- bioRxiv. 2024 Sep 19:2024.09.15.613155. [Abstract]
- bioRxiv. 2024 Aug 12:2024.08.12.607571. [Abstract]
- Res Sq. 2024 Jun 25.
- biorxiv. 2024 May 29.
- bioRxiv. 2024 Apr 25.
- bioRxiv. 2024 Feb 1:2024.02.01.578476. [Abstract]
- bioRxiv. 2023 Aug 11:2023.08.10.552800. [Abstract]
- bioRxiv. 2023 Jun 29.
- Res Sq. 2023 Apr 6:rs.3.rs-2688694. [Abstract]
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Actividad biológica
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DNA Polymerase |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| DLD-1 | EC50 |
>12 μM
Compound: 22; ART558
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Antiproliferative activity against human DLD-1 cells
Antiproliferative activity against human DLD-1 cells
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[PMID: 36200480] |
| DLD-1 | EC50 |
0.8 nM
Compound: 22; ART558
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Antiproliferative activity against human BRCA-2 deficient DLD-1 cells
Antiproliferative activity against human BRCA-2 deficient DLD-1 cells
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[PMID: 36200480] |
| HEK293 | EC50 |
180 nM
Compound: 22; ART558
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Inhibition of microhomology-mediated end joining in HEK293 cells
Inhibition of microhomology-mediated end joining in HEK293 cells
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[PMID: 36200480] |
ART558 (0-10 μM; 7 days; BRCA2wild-type or BRCA2-/- cells) shows synthetic lethality and a combinatorial effect with the PARPi olaparib in previously described isogenic models of BRCA1-deficiency[1].
ART558 (5 μM; 0-72 hours; BRCA2wild-type or BRCA2-/- cells) shows γH2AX accumulation in cells[1].
ART558 inhibits the major Polθ mediated DNA repair process, Theta-Mediated End Joining, without targeting NonHomologous End Joining. ART558 elicits DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumour cells and enhances the effects of a PARP inhibitor[1].
ART558 increases biomarkers of single-stranded DNA and synthetic lethality in 53BP1-defective cells whilst the inhibition of DNA nucleases that promote end-resection reversed these effects, implicating these in the synthetic lethal mechanism-of-action. ART558 increases the residence time of YFP-tagged full-length Polθ at sites of laserinduced DNA damage[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:BRCA2wild-type or BRCA2‒/‒ cells
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Concentration:0~10 μM
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Incubation Time:7 days
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Result:Showed synthetic lethality and a combinatorial effect with the PARPi olaparib in previously described isogenic models of BRCA1-deficiency.
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Cell Line:BRCA2wild-type or BRCA2‒/‒ cells
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Concentration:5μM
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Incubation Time:0~72 hours
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Result:Showed γH2AX accumulation in cells.
Chemical Information
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No. CAS 2603528-97-6
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Appearance Solid
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Peso molecular 418.41
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Fòrmula C21H21F3N4O2
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Color White to off-white
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SMILES
CN(C1=CC(C)=CC=C1)C([C@H]2N(C3=C(C(C(F)(F)F)=CC(C)=N3)C#N)CC[C@H]2O)=O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, sealed storage, away from moisture and light
* In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture and light)
Publications (50)
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Journal Impact Factor
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Most Recent
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Science
Different repair pathways support intact or truncated insertions by R2 retrotransposon protein. [Abstract]2026 Feb 26;391(6788):eadz3121. PMID: 41231928 -
Cell
Extrachromosomal DNA replication and maintenance couple with DNA damage pathway in tumors. [Abstract]2025 Jun 26;188(13):3405-3421.e27. PMID: 40300601 -
Nat Methods
2023 Sep;20(9):1388-1399. PMID: 37474806 -
Nat Cell Biol
Transcription-coupled DNA-protein crosslink repair by CSB and CRL4CSA-mediated degradation. [Abstract]2024 May;26(5):770-783. PMID: 38600236 -
Nat Commun
EP300 deficiency leads to chronic replication stress mediated by defective replication fork protection. [Abstract]2025 Dec 7. PMID: 41354653
ART558 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Dec 7. [Abstract]
Quantification of the percentage of Annexin V/PI-positive cells assessed by flow cytometry in EP300Mut, EP300WT NA-ATLL cells +/− POLQi (20 μM ART558 for 72 h) and +/− PARPi (10 μM Olaparib for 72 h) was performed.
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Nat Commun
Unveiling the cut-and-repair cycle of designer nucleases in human stem and T cells via CLEAR-time dPCR. [Abstract]2025 Nov 3;16(1):9571. PMID: 41184307
ART558 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2025 Nov 3;16(1):9571. [Abstract]
ART558 (3 μM; 24 h). Summary comparison between CLEAR-time dPCR (top) and ICE (bottom) 1, 3, and 14 days post-editing.
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Nat Commun
Polymerase theta repairs persistent G1-induced DNA breaks in S-phase during class switch recombination. [Abstract]2025 Nov 26;16(1):10536. PMID: 41298353 -
Nat Commun
2025 Jul 15;16(1):6502. PMID: 40664653 -
Nat Commun
HR eye & MMR eye: one-day assessment of DNA repair-defective tumors eligible for targeted therapy. [Abstract]2025 May 12;16(1):4239. PMID: 40355434 -
Nat Commun
Replication stress induces POLQ-mediated structural variant formation throughout common fragile sites after entry into mitosis. [Abstract]2024 Nov 6;15(1):9582. PMID: 39505880
ART558 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Nov 6;15(1):9582. [Abstract]
HCT116 M-phase deletion SV frequency with POLQ KO and inhibition by ART558 (5–10 µM; 5 h) and novobiocin (NVB) was measured.
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Nat Commun
PARG is essential for Polθ-mediated DNA end-joining by removing repressive poly-ADP-ribose marks. [Abstract]2024 Jul 11;15(1):5822. PMID: 38987289 -
Nat Commun
ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma. [Abstract]2024 Jun 21;15(1):5294. PMID: 38906885 -
Nat Commun
Polymerase θ inhibition activates the cGAS-STING pathway and cooperates with immune checkpoint blockade in models of BRCA-deficient cancer. [Abstract]2023 Mar 13;14(1):1390. PMID: 36914658
ART558 purchased from MedChemExpress. Usage Cited in: Nat Commun. 2023 Mar 13;14(1):1390. [Abstract]
ART558 (ART; 1 μM; 48 h)-mediated inhibition of POLθ leds to activation of the STING pathway in both MDA-MB-436 (left) and CAPAN-1 (right) cells.
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J Clin Invest
POLQ inhibition elicits an immune response in homologous recombination-deficient pancreatic adenocarcinoma via cGAS/STING signaling. [Abstract]2023 Jun 1;133(11):e165934. PMID: 36976649
ART558 purchased from MedChemExpress. Usage Cited in: J Clin Invest. 2023 Jun 1;133(11):e165934. [Abstract]
ART558 (0-2 μM; 6 days) effectively decreases cell viability and inhibits colony formation in colorectal adenocarcinoma cells (DLD-1) with a truncating mutation in BRCA2.
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Nucleic Acids Res
PARP1 and PARP2 are dispensable for DNA repair by microhomology-mediated end-joining at double-ended DSBs. [Abstract]2026 Jan 5;54(1):gkaf1437. PMID: 41495903 -
Nucleic Acids Res
Single-stranded DNA with internal base modifications mediates highly efficient knock-in in primary cells using CRISPR-Cas9. [Abstract]2024 Nov 21:gkae1069. PMID: 39569586 -
Nucleic Acids Res
Novel BRCA1-PLK1-CIP2A axis orchestrates homologous recombination-mediated DNA repair to maintain chromosome integrity during oocyte meiosis. [Abstract]2024 Dec 9:gkae1207. PMID: 39657788 -
Cell Rep Med
2026 Mar 17;7(3):102687. PMID: 41850232 -
Proc Natl Acad Sci U S A
HPV16 E6 oncoprotein promotes microhomology-mediated viral integration by increasing PolΘ protein expression. [Abstract]2026 Mar 10;123(10):e2532479123. PMID: 41785316 -
Genes Dev
WRN exonuclease imparts high fidelity on translesion synthesis by Y family DNA polymerases. [Abstract]2024 Apr 17;38(5-6):213-232. PMID: 38503516 -
J Transl Med
Polymerase theta inhibition impairs tumor growth and amplifies melphalan-induced DNA damage in multiple myeloma. [Abstract]2025 Oct 10;23(1):1079. PMID: 41074018 -
Cell Rep
Fanconi anemia-associated chromosomal radial formation is dependent on POLθ-mediated alternative end joining. [Abstract]2023 Apr 21;42(5):112428. PMID: 37086407 -
Int J Mol Sci
Polθ Inhibitor (ART558) Demonstrates a Synthetic Lethal Effect with PARP and RAD52 Inhibitors in Glioblastoma Cells. [Abstract]2024 Aug 23;25(17):9134. PMID: 39273083 -
DNA Repair
2025 Sep:153:103889. PMID: 40913914 -
Surgery
Overexpression of human DNA polymerase theta is a biomarker of aggressive and DNA repair-deficient papillary thyroid cancers. [Abstract]2024 Jun 18:S0039-6060(24)00303-9. PMID: 38897886 -
Gene
2023 Dec 20:888:147762. PMID: 37666373 -
Pathologie (Heidelb)
POLQ and DNA-PK inhibition in muscle-invasive bladder cancer : Enhancing radiosensitivity with novel DNA damage response inhibitors to improve radiotherapy outcomes. [Abstract]2025 Nov 26. PMID: 41295990 -
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bioRxiv
2026 Jan 23:2026.01.22.701150. PMID: 41648153 -
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bioRxiv
2025 Nov 21:2025.11.20.689563. PMID: 41332615 -
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bioRxiv
PARP1 and PARP2 are dispensable for DNA repair by microhomology-mediated end-joining during mitosis. [Abstract]2025 Jun 9:2025.06.09.658719. PMID: 40661535 -
bioRxiv
2025 May 10:2025.05.06.651696. PMID: 40568108 -
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bioRxiv
DNA polymerase theta-mediated DNA repair is a functional dependency and therapeutic vulnerability in DNMT3A deficient leukemia cells. [Abstract]2024 Sep 19:2024.09.15.613155. PMID: 39411165 -
bioRxiv
DNA-PKcs Inhibition Improves Sequential Gene Insertion of the Full-Length CFTR cDNA in Airway Stem Cells. [Abstract]2024 Aug 12:2024.08.12.607571. PMID: 39185207 -
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bioRxiv
Single-Stranded DNA with Internal Base Modifications Mediates Highly Efficient Gene Insertion in Primary Cells. [Abstract]2024 Feb 1:2024.02.01.578476. PMID: 38352420 -
bioRxiv
Non-homologous end joining shapes the genomic rearrangement landscape of chromothripsis from mitotic errors. [Abstract]2023 Aug 11:2023.08.10.552800. PMID: 37609143 -
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Res Sq
Haploinsufficiency of ZNF251 causes DNA-PKcs-dependent resistance to PARP inhibitors in BRCA1-mutated cancer cells. [Abstract]2023 Apr 6:rs.3.rs-2688694. PMID: 37066268
Solvente y solubilidad
DMSO : 170 mg/mL (406.30 mM; Need ultrasonic; 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, 2 years; -20°C, 1 year (sealed storage, away from moisture and light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year (sealed storage, away from moisture and light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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: 4.25 mg/mL (10.16 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 4.25 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (42.5 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.
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, 2 years; -20°C, 1 year (sealed storage, away from moisture and 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.
Pureza y Documentación
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Ficha de datos (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 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, 2 years; -20°C, 1 year (sealed storage, away from moisture and light). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3900 mL | 11.9500 mL | 23.9000 mL | 59.7500 mL |
| 5 mM | 0.4780 mL | 2.3900 mL | 4.7800 mL | 11.9500 mL | |
| 10 mM | 0.2390 mL | 1.1950 mL | 2.3900 mL | 5.9750 mL | |
| 15 mM | 0.1593 mL | 0.7967 mL | 1.5933 mL | 3.9833 mL | |
| 20 mM | 0.1195 mL | 0.5975 mL | 1.1950 mL | 2.9875 mL | |
| 25 mM | 0.0956 mL | 0.4780 mL | 0.9560 mL | 2.3900 mL | |
| 30 mM | 0.0797 mL | 0.3983 mL | 0.7967 mL | 1.9917 mL | |
| 40 mM | 0.0598 mL | 0.2988 mL | 0.5975 mL | 1.4938 mL | |
| 50 mM | 0.0478 mL | 0.2390 mL | 0.4780 mL | 1.1950 mL | |
| 60 mM | 0.0398 mL | 0.1992 mL | 0.3983 mL | 0.9958 mL | |
| 80 mM | 0.0299 mL | 0.1494 mL | 0.2988 mL | 0.7469 mL | |
| 100 mM | 0.0239 mL | 0.1195 mL | 0.2390 mL | 0.5975 mL |
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