Tandutinib
Based on 5 publication(s) in Google Scholar
Tandutinib (MLN518) is a potent and selective inhibitor of the FLT3 with an IC50 of 0.22 μM, and also inhibits c-Kit and PDGFR with IC50s of 0.17 μM and 0.20 μM, respectively. Tandutinib can be used for acute myelogenous leukemia (AML). Tandutinib has the ability to cross the blood-brain barrier.
For research use only. We do not sell to patients.
- Purity: 99.48%
- CAS No.: 387867-13-2
- Formula: C31H42N6O4
- Molecular Weight:562.70
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
Publications Citing Use of MedChemExpress (MCE) Tandutinib
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Biological Activity
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PDGFR 0.2 μM (IC50) |
FLT3 0.22 μM (IC50) |
c-Kit 0.17 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A-375 | IC50 |
>10000 nM
Compound: MLN-518
|
Toxicity against human A375 cells after 72 hrs by cell titer-blue assay
Toxicity against human A375 cells after 72 hrs by cell titer-blue assay
|
[PMID: 19654408] |
| A549 | IC50 |
14.75 μM
Compound: Tandutinib
|
Antiproliferative activity against human A549 cells after 72 hrs by MTS assay
Antiproliferative activity against human A549 cells after 72 hrs by MTS assay
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[PMID: 27575478] |
| BaF3 | IC50 |
10 nM
Compound: Tandutinib
|
Antiproliferative activity against mouse BaF3 cells expressing FLT3-ITD mutant assessed as inhibition of cell proliferation measured after 72 hrs by celltiter-glo luminescent cell viability assay
Antiproliferative activity against mouse BaF3 cells expressing FLT3-ITD mutant assessed as inhibition of cell proliferation measured after 72 hrs by celltiter-glo luminescent cell viability assay
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[PMID: 32659083] |
| CHO | IC50 |
0.17 μM
Compound: 75
|
Inhibition of chimeric PDGF receptor with c-kit cytoplasmic domain phosphorylation in CHO cells
Inhibition of chimeric PDGF receptor with c-kit cytoplasmic domain phosphorylation in CHO cells
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[PMID: 12166950] |
| CHO | IC50 |
0.2 μM
Compound: 75
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Inhibition of wild type Platelet-derived growth factor receptor beta phosphorylation in CHO cells
Inhibition of wild type Platelet-derived growth factor receptor beta phosphorylation in CHO cells
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[PMID: 12166950] |
| CHO | IC50 |
0.22 μM
Compound: 75
|
Inhibition of chimeric PDGF receptor with FLT-3 cytoplasmic domain phosphorylation in CHO cells
Inhibition of chimeric PDGF receptor with FLT-3 cytoplasmic domain phosphorylation in CHO cells
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[PMID: 12166950] |
| CHO | IC50 |
3.43 μM
Compound: 75
|
Inhibition of chimeric PDGF receptor with CSF-1R cytoplasmic domain phosphorylation in CHO cells
Inhibition of chimeric PDGF receptor with CSF-1R cytoplasmic domain phosphorylation in CHO cells
|
[PMID: 12166950] |
| HCT-116 | IC50 |
18.13 μM
Compound: Tandutinib
|
Antiproliferative activity against human HCT116 cells after 72 hrs by MTS assay
Antiproliferative activity against human HCT116 cells after 72 hrs by MTS assay
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[PMID: 27575478] |
| HL-60 | GI50 |
>10 μM
Compound: MLN518
|
Growth inhibition of human HL60 cells after 48 hrs by XTT assay
Growth inhibition of human HL60 cells after 48 hrs by XTT assay
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[PMID: 25108079] |
| K562 | GI50 |
>10 μM
Compound: MLN518
|
Growth inhibition of human K562 cells after 48 hrs by XTT assay
Growth inhibition of human K562 cells after 48 hrs by XTT assay
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[PMID: 25108079] |
| K562 | IC50 |
>10000 nM
Compound: MLN-518
|
Antiproliferative activity against FLT3-deficient human K562 cells after 72 hrs by MTT assay
Antiproliferative activity against FLT3-deficient human K562 cells after 72 hrs by MTT assay
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[PMID: 27266526] |
| K562 | IC50 |
9.21 μM
Compound: MLN518
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Antiproliferative activity against human K562 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luminescent cell viability assay
Antiproliferative activity against human K562 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luminescent cell viability assay
|
[PMID: 31614258] |
| Kasumi 1 | IC50 |
0.022 μM
Compound: MLN-518
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Antiproliferative activity against human Kasumi-1 cells after 72 hrs by MTT assay
Antiproliferative activity against human Kasumi-1 cells after 72 hrs by MTT assay
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[PMID: 20570526] |
| Leukemia cell | IC50 |
0.29 μM
Compound: 2
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Cytotoxicity against human primary leukemia cells isolated from acute myeloid leukemia patient expressing FLT3-ITD mutation assessed as cell viability after 72 hrs by luciferase assay
Cytotoxicity against human primary leukemia cells isolated from acute myeloid leukemia patient expressing FLT3-ITD mutation assessed as cell viability after 72 hrs by luciferase assay
|
[PMID: 22221201] |
| Leukemia cell | IC50 |
0.64 μM
Compound: 2
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Cytotoxicity against human primary leukemia cells isolated from acute myeloid leukemia patient expressing wild type FLT3 assessed as cell viability after 72 hrs by luciferase assay
Cytotoxicity against human primary leukemia cells isolated from acute myeloid leukemia patient expressing wild type FLT3 assessed as cell viability after 72 hrs by luciferase assay
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[PMID: 22221201] |
| Leukemia cell | IC50 |
3.4 μM
Compound: 2
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Cytotoxicity against human primary leukemia cells isolated from acute myeloid leukemia patient expressing FLT3-D835Y mutation assessed as cell viability after 72 hrs by luciferase assay
Cytotoxicity against human primary leukemia cells isolated from acute myeloid leukemia patient expressing FLT3-D835Y mutation assessed as cell viability after 72 hrs by luciferase assay
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[PMID: 22221201] |
| MCF7 | IC50 |
14.7 μM
Compound: Tandutinib
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Antiproliferative activity against human MCF7 cells after 72 hrs by MTS assay
Antiproliferative activity against human MCF7 cells after 72 hrs by MTS assay
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[PMID: 27575478] |
| MG-63 | IC50 |
0.026 μM
Compound: 75
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Inhibition of platelet-derived growth factor receptor beta phosphorylation in MG63 cells in the absence of plasma
Inhibition of platelet-derived growth factor receptor beta phosphorylation in MG63 cells in the absence of plasma
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[PMID: 12166950] |
| MG-63 | IC50 |
0.036 μM
Compound: 75
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Inhibition of platelet derived growth factor receptor beta phosphorylation in MG63 cells in the presence of human plasma
Inhibition of platelet derived growth factor receptor beta phosphorylation in MG63 cells in the presence of human plasma
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[PMID: 12166950] |
| MOLM-13 | IC50 |
0.081 μM
Compound: MLN-518
|
Antiproliferative activity against human MOLM13 cells after 72 hrs by MTT assay
Antiproliferative activity against human MOLM13 cells after 72 hrs by MTT assay
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[PMID: 20570526] |
| MOLM-13 | IC50 |
10 nM
Compound: Tandutinib
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Antiproliferative activity against human MOLM-13 cells expressing FLT3-ITD mutant assessed as inhibition of cell proliferation measured after 72 hrs by celltiter-glo luminescent cell viability assay
Antiproliferative activity against human MOLM-13 cells expressing FLT3-ITD mutant assessed as inhibition of cell proliferation measured after 72 hrs by celltiter-glo luminescent cell viability assay
|
[PMID: 32659083] |
| MOLM-13 | GI50 |
0.052 μM
Compound: MLN518
|
Antiproliferative activity against human MOLM-13 cells assessed as reduction in cell viability after 72 hrs by MTS assay
Antiproliferative activity against human MOLM-13 cells assessed as reduction in cell viability after 72 hrs by MTS assay
|
[PMID: 32975953] |
| MOLM-13 | GI50 |
1.9 μM
Compound: MLN518
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Antiproliferative activity against human MOLM-13 cells harboring D835Y mutant assessed as reduction in cell viability after 72 hrs by MTS assay
Antiproliferative activity against human MOLM-13 cells harboring D835Y mutant assessed as reduction in cell viability after 72 hrs by MTS assay
|
[PMID: 32975953] |
| MOLM-14 | IC50 |
10 nM
Compound: Tandutinib
|
Antiproliferative activity against human MOLM-14 cells expressing FLT3-ITD mutant assessed as inhibition of cell proliferation measured after 72 hrs by celltiter-glo luminescent cell viability assay
Antiproliferative activity against human MOLM-14 cells expressing FLT3-ITD mutant assessed as inhibition of cell proliferation measured after 72 hrs by celltiter-glo luminescent cell viability assay
|
[PMID: 32659083] |
| MV4-11 | IC50 |
60 nM
Compound: MLN-518
|
Cytotoxicity against human MV4-11 cells after 72 hrs by cell titer-blue assay
Cytotoxicity against human MV4-11 cells after 72 hrs by cell titer-blue assay
|
[PMID: 19654408] |
| MV4-11 | IC50 |
0.119 μM
Compound: MLN-518
|
Antiproliferative activity against human MV4-11 cells after 72 hrs by MTT assay
Antiproliferative activity against human MV4-11 cells after 72 hrs by MTT assay
|
[PMID: 20570526] |
| MV4-11 | IC50 |
0.055 μM
Compound: MLN518
|
Cytotoxicity against FLT3-dependent human MV4-11 cells after 72 hrs by MTT assay
Cytotoxicity against FLT3-dependent human MV4-11 cells after 72 hrs by MTT assay
|
[PMID: 22452518] |
| MV4-11 | GI50 |
8.756 μM
Compound: MLN518
|
Growth inhibition of human MV411 cells after 48 hrs by XTT assay
Growth inhibition of human MV411 cells after 48 hrs by XTT assay
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[PMID: 25108079] |
| MV4-11 | IC50 |
302 nM
Compound: MLN-518
|
Antiproliferative activity against human MV4-11 cells harboring FLT3-ITD mutant after 72 hrs by MTT assay
Antiproliferative activity against human MV4-11 cells harboring FLT3-ITD mutant after 72 hrs by MTT assay
|
[PMID: 27266526] |
| MV4-11 | IC50 |
0.06 μM
Compound: MLN518
|
Antiproliferative activity against human MV4-11 cells harboring FLT3 ITD mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luminescent cell viability assay
Antiproliferative activity against human MV4-11 cells harboring FLT3 ITD mutant assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luminescent cell viability assay
|
[PMID: 31614258] |
| P815 | IC50 |
600 nM
Compound: 3
|
Cytotoxicity in mouse P815 cells expressing KIT D814Y mutant assessed as reduction in cell viability incubated for 48 hrs by MTT assay
Cytotoxicity in mouse P815 cells expressing KIT D814Y mutant assessed as reduction in cell viability incubated for 48 hrs by MTT assay
|
[PMID: 29678462] |
| RS4-11 | IC50 |
170 nM
Compound: MLN-518
|
Inhibition of FLT3 autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay
Inhibition of FLT3 autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay
|
[PMID: 19654408] |
| RS4-11 | IC50 |
33 nM
Compound: MLN-518
|
Inhibition of FLT3 ITD mutant autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay
Inhibition of FLT3 ITD mutant autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay
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[PMID: 19654408] |
| RS4-11 | IC50 |
>5 μM
Compound: MLN-518
|
Antiproliferative activity against human RS4:11 cells after 72 hrs by MTT assay
Antiproliferative activity against human RS4:11 cells after 72 hrs by MTT assay
|
[PMID: 20570526] |
| Sf9 | IC50 |
0.22 μM
Compound: 19; MLN518, CT53518
|
Inhibition of N-terminal GST-tagged human FLT3 (563 to 993 residues) cytoplasmic domain expressed in baculovirus infected sf9 cells using EAIYAAPFAKKK as substrate after 10 mins in presence of [gamma-33P]-ATP by scintillation counting method
Inhibition of N-terminal GST-tagged human FLT3 (563 to 993 residues) cytoplasmic domain expressed in baculovirus infected sf9 cells using EAIYAAPFAKKK as substrate after 10 mins in presence of [gamma-33P]-ATP by scintillation counting method
|
[PMID: 31207462] |
| THP-1 | IC50 |
1 μM
Compound: MLN-518
|
Antiproliferative activity against human THP1 cells after 72 hrs by MTT assay
Antiproliferative activity against human THP1 cells after 72 hrs by MTT assay
|
[PMID: 20570526] |
| THP-1 | GI50 |
>10 μM
Compound: MLN518
|
Growth inhibition of human THP1 cells after 48 hrs by XTT assay
Growth inhibition of human THP1 cells after 48 hrs by XTT assay
|
[PMID: 25108079] |
| U-937 | IC50 |
>5 μM
Compound: MLN-518
|
Antiproliferative activity against human U937 cells after 72 hrs by MTT assay
Antiproliferative activity against human U937 cells after 72 hrs by MTT assay
|
[PMID: 20570526] |
| U-937 | IC50 |
19.8 μM
Compound: MLN518
|
Antiproliferative activity against human U937 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luminescent cell viability assay
Antiproliferative activity against human U937 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luminescent cell viability assay
|
[PMID: 31614258] |
| WI-38 | IC50 |
>10000 nM
Compound: MLN-518
|
Antiproliferative activity against human WI38 cells after 72 hrs by SRB assay
Antiproliferative activity against human WI38 cells after 72 hrs by SRB assay
|
[PMID: 27266526] |
Tandutinib (0-3 μM; 30 minutes; Ba/F3 cells) treatment inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC50 of 10-100 nM in Ba/F3 cells expressing different FLT3-ITD mutants[1].
Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells[1].
In human FLT3-ITD-positive AML cell lines, Tandutinib inhibits FLT3-ITD phosphorylation (IC50 of ~30 nM). As with Erk2, a constitutively high level of Akt phosphorylation is readily detected and is efficiently blocked by pretreatment of the Molm-14 cells with 100-300 nM Tandutinib[1].
Tandutinib inhibits cell proliferation of the FLT3-ITD-positive Molm-13 and Molm-14 with an IC50 of 10 nM. And signaling through the MAP kinase and PI3 kinase pathways[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Molm-14 and THP-1 AML cells
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Concentration:1 μM
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Incubation Time:24 hours, 48 hours, 72 hours, 96 hours
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Result:Induced apoptosis in FLT3-ITD-positive AML cells.
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Cell Line:Ba/F3 cells
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Concentration:0 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 1 μM and 3 μM
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Incubation Time:30 minutes
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Result:In Ba/F3 cells expressing different FLT3-ITD mutants, inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Athymic nude mice injected with Ba/F3 cells[1]
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Dosage:60 mg/kg
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Administration:Oral gavage; daily; for 35 days
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Result:Caused a statistically significant increase in survival that was extended on average by 20 days.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 387867-13-2
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Appearance Solid
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Molecular Weight 562.70
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Formula C31H42N6O4
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Color White to light yellow
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SMILES
O=C(N1CCN(C2=C(C(C=C3OCCCN4CCCCC4)=NC=N2)C=C3OC)CC1)NC5=CC=C(OC(C)C)C=C5
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Synonyms
MLN518; CT53518
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (5)
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Journal Impact Factor
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Most Recent
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Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
Drug Des Devel Ther
LC-MS/MS Estimation of the Anti-Cancer Agent Tandutinib Levels in Human Liver Microsomes: Metabolic Stability Evaluation Assay. [Abstract]2020 Oct 23;14:4439-4449. PMID: 33122888 -
Drug Des Devel Ther
Advances in the drug therapies of acute myeloid leukemia (except acute wpromyelocytic leukemia). [Abstract]2018 Apr 30:12:1009-1017. PMID: 29750014 -
Cancers (Basel)
Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell Carcinoma. [Abstract]2022 Nov 28;14(23):5854. PMID: 36497337 -
Biochem Biophys Res Commun
2017 Aug 19;490(2):209-216. PMID: 28601636
Solvent & Solubility
DMSO : 50 mg/mL (88.86 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. 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. 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: ≥ 2.5 mg/mL (4.44 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (4.44 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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-
-
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%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.
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.
Purity & Documentation
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Data Sheet (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)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Kelly LM, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell, 2002, 1(5), 421-432. [Content Brief]
[2]. Griswold IJ, et al. Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood, 2004, 104(9), 2912-2918. [Content Brief]
[3]. Yang JJ, et al. P-glycoprotein and breast cancer resistance protein affect disposition of tandutinib, a tyrosine kinase inhibitor. Drug Metab Lett. 2010 Dec;4(4):201-12. [Content Brief]
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. 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 | 1.7771 mL | 8.8857 mL | 17.7715 mL | 44.4286 mL |
| 5 mM | 0.3554 mL | 1.7771 mL | 3.5543 mL | 8.8857 mL | |
| 10 mM | 0.1777 mL | 0.8886 mL | 1.7771 mL | 4.4429 mL | |
| 15 mM | 0.1185 mL | 0.5924 mL | 1.1848 mL | 2.9619 mL | |
| 20 mM | 0.0889 mL | 0.4443 mL | 0.8886 mL | 2.2214 mL | |
| 25 mM | 0.0711 mL | 0.3554 mL | 0.7109 mL | 1.7771 mL | |
| 30 mM | 0.0592 mL | 0.2962 mL | 0.5924 mL | 1.4810 mL | |
| 40 mM | 0.0444 mL | 0.2221 mL | 0.4443 mL | 1.1107 mL | |
| 50 mM | 0.0355 mL | 0.1777 mL | 0.3554 mL | 0.8886 mL | |
| 60 mM | 0.0296 mL | 0.1481 mL | 0.2962 mL | 0.7405 mL | |
| 80 mM | 0.0222 mL | 0.1111 mL | 0.2221 mL | 0.5554 mL |