MLN0905Potent PLK1 inhibitor CAS# 1228960-69-7 |
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 1228960-69-7 | SDF | Download SDF |
PubChem ID | 46235922 | Appearance | Powder |
Formula | C24H25F3N6S | M.Wt | 486.56 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | PLK1 Inhibitor | ||
Solubility | Soluble in DMSO > 10 mM | ||
Chemical Name | 2-[[5-[3-(dimethylamino)propyl]-2-methylpyridin-3-yl]amino]-9-(trifluoromethyl)-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione | ||
SMILES | CC1=C(C=C(C=N1)CCCN(C)C)NC2=NC=C3CC(=S)NC4=C(C3=N2)C=CC(=C4)C(F)(F)F | ||
Standard InChIKey | CODBZFJPKJDNDT-UHFFFAOYSA-N | ||
Standard InChI | 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) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | MLN0905 is a potent inhibitor of PLK1 with IC50 of 2 nM. | |||||
Targets | PLK1 | |||||
IC50 | 2 nM |
MLN0905 Dilution Calculator
MLN0905 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.0552 mL | 10.2762 mL | 20.5524 mL | 41.1049 mL | 51.3811 mL |
5 mM | 0.411 mL | 2.0552 mL | 4.1105 mL | 8.221 mL | 10.2762 mL |
10 mM | 0.2055 mL | 1.0276 mL | 2.0552 mL | 4.1105 mL | 5.1381 mL |
50 mM | 0.0411 mL | 0.2055 mL | 0.411 mL | 0.8221 mL | 1.0276 mL |
100 mM | 0.0206 mL | 0.1028 mL | 0.2055 mL | 0.411 mL | 0.5138 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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MLN0905 is a potent inhibitor of PLK1 with IC50 value ranges from 3 to 24 nM [1].
Polo-like kinase 1 (PLK1) is a family of conserved serine/threonine kinases and plays an important role in regulating cell cycle. It has been revealed that PLK1 drives cell cycle progression by triggerting G2/M transition and is considered as a pro-oncogene which overexpressed in tumor cells [2].
MLN0905 is a selective PLK1 inhibitor and has similar effect as RNAi hnockdown. When tested with HT-29 cells, MLN0905 treatment significantly increased pHisH3 expression which indicated that cells were arrested in G2/M phase by inhibiting PLK1 expression [1].
In mouse model with human diffuse large B-cell lymphoma (DLBCL) cell line OCILY-19 subcutaneous xenograft, co-administration of MLN0905 and rituximab markedly reduced tumor volume and increased survival time through inhibiting PLK1 which resulted in mitotic arrest [1]. And the same result was achieved when using nude mice model with human colon tumor HT29 xenograft, MLN0905 treatment significantly inhibited tumor growth or progression [3].
References:
[1]. Shi, J.Q., et al., MLN0905, a small-molecule plk1 inhibitor, induces antitumor responses in human models of diffuse large B-cell lymphoma. Mol Cancer Ther, 2012. 11(9): p. 2045-53.
[2]. Espeut, J., et al., Natural Loss of Mps1 Kinase in Nematodes Uncovers a Role for Polo-like Kinase 1 in Spindle Checkpoint Initiation. Cell Rep, 2015.
[3]. Duffey, M.O., et al., Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905). J Med Chem, 2012. 55(1): p. 197-208.
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Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905).[Pubmed:22070629]
J Med Chem. 2012 Jan 12;55(1):197-208.
This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.
MLN0905, a small-molecule plk1 inhibitor, induces antitumor responses in human models of diffuse large B-cell lymphoma.[Pubmed:22609854]
Mol Cancer Ther. 2012 Sep;11(9):2045-53.
Diffuse large B-cell lymphoma (DLBCL) is the most common of the non-Hodgkin lymphomas, accounting for up to 30% of all newly diagnosed lymphoma cases. Current treatment options for this disease are effective, but not always curative; therefore, experimental therapies continue to be investigated. We have discovered an experimental, potent, and selective small-molecule inhibitor of PLK1, MLN0905, which inhibits cell proliferation in a broad range of human tumor cells including DLBCL cell lines. In our report, we explored the pharmacokinetic, pharmacodynamic, and antitumor properties of MLN0905 in DLBCL xenograft models grown in mice. These studies indicate that MLN0905 modulates the pharmacodynamic biomarker phosphorylated histone H3 (pHisH3) in tumor tissue. The antitumor activity of MLN0905 was evaluated in three human subcutaneous DLBCL xenograft models, OCI LY-10, OCI LY-19, and PHTX-22L (primary lymphoma). In each model, MLN0905 yielded significant antitumor activity on both a continuous (daily) and intermittent dosing schedule, underscoring dosing flexibility. The antitumor activity of MLN0905 was also evaluated in a disseminated xenograft (OCI LY-19) model to better mimic human DLBCL disease. In the disseminated model, MLN0905 induced a highly significant survival advantage. Finally, MLN0905 was combined with a standard-of-care agent, rituximab, in the disseminated OCI LY-19 xenograft model. Combining rituximab and MLN0905 provided both a synergistic antitumor effect and a synergistic survival advantage. Our findings indicate that PLK1 inhibition leads to pharmacodynamic pHisH3 modulation and significant antitumor activity in multiple DLBCL models. These data strongly suggest evaluating PLK1 inhibitors as DLBCL anticancer agents in the clinic.