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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
MLN0905 (MLN-0905; MLN 0905) is a novel, potent and selective small-molecule inhibitor of polo-like kinase-1 (PLK1) with potential antineoplastic activity. Its IC50 is 2 nM, which inhibits PLK1. A wide variety of human tumor cells, including DLBCL cell lines, are inhibited in their ability to proliferate by MLN0905. In several DLBCL models, pharmacodynamic pHisH3 modulation and strong antitumor activity are the results of PLK1 inhibition. These findings strongly support testing PLK1 inhibitors as DLBCL anticancer drugs in clinical settings.
| Targets |
PLK1 (IC50 = 2 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
Thirty microliters of human PLK1 enzymatic reaction were used, along with 50 mM Tris-HCl (pH 8.0), 10 mM MgCl2, 0.02% BSA, 10% glycerol, 1 mM DTT, 100 mM NaCl, 3.3% DMSO, eight microliters of ATP, 0.2 microliters of [γ-33P]-ATP, four microliters of peptide substrate (Biotin-AHX-LDETGHLDSSGLQEVHLA-CONH2), and ten nanoliters of recombinant human PLK1[2–369]T210D. PLK inhibitors or not, the enzymatic reaction mixture is incubated for 2.5 hours at 30 degrees Celsius before being stopped with 20 microliters of 150 mM EDTA. After that, 25μL of the stopped enzyme reaction mixture is put on an Image FlashPlate coated with streptavidin that has 384 wells, and it is left to sit at room temperature for three hours. After three Tween-20 washes (0.02%), the Image Flash Plate wells are read using a Perkin-Elmer Viewlux.
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| Cell Assay |
MLN0905 functions similarly to RNAi knockdown and is a selective PLK1 inhibitor. MLN0905 treatment dramatically increased pHisH3 expression in HT-29 cells, indicating that PLK1 expression was inhibited and cell arrest in the G2/M phase resulted.
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| Animal Protocol |
Tumor (HT29) xenograft model
0-50 mg/kg P.O; daily, QD×3/week |
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| References |
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| Molecular Formula |
C24H25F3N6S
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| Molecular Weight |
486.56
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| Exact Mass |
486.181
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| Elemental Analysis |
C, 59.24; H, 5.18; F, 11.71; N, 17.27; S, 6.59
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| CAS # |
1228960-69-7
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| Related CAS # |
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| PubChem CID |
46235922
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
624.4±65.0 °C at 760 mmHg
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| Flash Point |
331.4±34.3 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.640
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| LogP |
4.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
692
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=NC=C(CCCN(C)C)C=C1NC2=NC(C(C=CC(C(F)(F)F)=C3)=C3NC(C4)=S)=C4C=N2
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| InChi Key |
CODBZFJPKJDNDT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H25F3N6S/c1-14-19(9-15(12-28-14)5-4-8-33(2)3)31-23-29-13-16-10-21(34)30-20-11-17(24(25,26)27)6-7-18(20)22(16)32-23/h6-7,9,11-13H,4-5,8,10H2,1-3H3,(H,30,34)(H,29,31,32)
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| Chemical Name |
2-[[5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl]amino]-9-(trifluoromethyl)-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione
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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 (5.14 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 (5.14 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 (5.14 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 | 2.0552 mL | 10.2762 mL | 20.5524 mL | |
| 5 mM | 0.4110 mL | 2.0552 mL | 4.1105 mL | |
| 10 mM | 0.2055 mL | 1.0276 mL | 2.0552 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.
MLN0905 induces a significant antitumor response in mice bearing disseminated (human) OCI LY-19-Luc lymphoma disease.
pHisH3 was used as a biomarker to determine the level of mitotic arrest in OCI LY-19-Luc xenograft tumors.Mol Cancer Ther.2012 Sep;11(9):2045-53. |
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MLN0905, a small-molecule inhibitor of PLK1, phenocopies the effects of PLK1 knockdown using RNAi in HT-29 cells.
MLN0905 induces a significant antitumor response in a primary human lymphoma model (PHTX-22L).Mol Cancer Ther.2012 Sep;11(9):2045-53. |
MLN0905 and rituximab yield a synergistic antitumor response in a disseminated xenograft model of human lymphoma (OCI LY-19-Luc).
Evaluating the effect of dosing schedule versus antitumor effect with MLN0905 in the OCI LY-10 subcutaneous tumor model.Mol Cancer Ther.2012 Sep;11(9):2045-53. |
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