product name Alisertib
Description: Alisertib (also named as MLN8237) is a selective, orally bioavailable Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Alisertib was developed from its predecessor, MLN8054, in order to minimize the benzodiazepine-like effects seen with MLN8054. The inhibitory effect of Alisertib is ATP-competitive, reversible and AAK-specific with an inhibition constant (Ki) of 0.43 nmol/L. MLN8237 is being investigated to treat advanced cancers.
References: Blood. 2010 Jun 24;115(25):5202-13; Clin Cancer Res. 2011 Dec 15;17(24):7614-24; Mol Cancer Ther. 2012 Mar;11(3):763-74.
518.92
Formula
C27H20ClFN4O4
CAS No.
1028486-01-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 27 mg/mL (52.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
15% Captisol: 5 mg/mL
Synonyms
MLN8237
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19393378
| In Vitro |
In vitro activity: MLN8237 shows >200-fold higher selectivity for Aurora A than the structurally related Aurora B with an IC50 of 396.5 nM, and does not have any significant activity against 205 other kinases. MLN8237 (0.5 μM) treatment inhibits the phosphorylation of Aurora A in MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. MLN8237 significantly inhibits cell proliferation in multiple myeloma (MM) cell lines with IC50 values of 0.003-1.71 μM. MLN8237 displays more potent anti-proliferation activity against primary MM cells and MM cell lines in the presence of BM stroma cells, as well as IL-6 and IGF-1 than against MM cells alone. MLN8237 (0.5 μM) induces 2- to 6-fold increase in G2/M phase in primary MM cells and cell lines, as well as significant apoptosis and senescence, involving the up-regulation of p53, p21 and p27, as well as PARP, caspase 3, and caspase 9 cleavage. In addition, MLN8237 shows strong synergistic anti-MM effect with dexamethasone, as well as additive effect with doxorubicin and bortezomib. MLN8237 (0.5 μM) treatment causes the inhibition of colony formation of FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, and induces a significant increase in the percentage of polyploid cells, and subsequently an increase in the percentage of cells in the sub-G1 phase, which can be further enhanced in combination with cisplatin (2.5 μM), involving the higher induction of TAp73β, PUMA, NOXA, cleaved caspase-3, and cleaved PARP as compared with a single-agent treatment.. Kinase Assay: Aurora A radioactive Flashplate enzyme assay is conducted to determine the nature and degree of MLN8237-mediated inhibition in vitro. Recombinant Aurora A is expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A is conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) is assayed in 50 mM Hepes (pH 7.5), 10 mM MgCl2, 5 mM DTT, 0.05% Tween 20, 2 μM peptide substrate, 3.3 μCi/mL [γ-33P]ATP at 2 μM, and increasing concentrations of MLN8237 by using Image FlashPlates. Cell Assay: Cells are exposed to various concentrations of MLN8237 for 24, 48, and 72 hours. Cells viability is measured using MTT assay, and cell proliferation is measured using 3[H]-thymidine incorporation. For cell cycle analysis, cells are permeabilized by 70% ethanol at -20 °C, and incubated with 50 μg/mL PI and 20 units/mL RNase-A. DNA content is analyzed by flow cytometry using BDFACS-Canto II and FlowJo software. For the detection of apoptosis and senescence, cells are stained with fluorescein isothiocyanate-annexin V and PI. Apoptotic cells are determined by flow cytometric analysis using BDFACS-Canto II and FlowJo software. |
|---|---|
| In Vivo | MLN8237 significantly reduces the tumor burden with tumor growth inhibition (TGI) of 42% and 80% at 15 mg/kg and 30 mg/kg, respectively, and prolongs the survival of mice compared with the control. |
| Animal model | Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells |
| Formulation & Dosage | Dissolved in 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate; 30 mg/kg; Oral gavage |
| References | Blood. 2010 Jun 24;115(25):5202-13; Clin Cancer Res. 2011 Dec 15;17(24):7614-24; Mol Cancer Ther. 2012 Mar;11(3):763-74. |
Related Posts
product name Alisertib
Description: Alisertib (also named as MLN8237) is a selective, orally bioavailable Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Alisertib was developed from its predecessor, MLN8054, in order to minimize the benzodiazepine-like effects seen with MLN8054. The inhibitory effect of Alisertib is ATP-competitive, reversible and AAK-specific with an inhibition constant (Ki) of 0.43 nmol/L. MLN8237 is being investigated to treat advanced cancers.
References: Blood. 2010 Jun 24;115(25):5202-13; Clin Cancer Res. 2011 Dec 15;17(24):7614-24; Mol Cancer Ther. 2012 Mar;11(3):763-74.
518.92
Formula
C27H20ClFN4O4
CAS No.
1028486-01-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 27 mg/mL (52.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
15% Captisol: 5 mg/mL
Synonyms
MLN8237
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19393378
| In Vitro |
In vitro activity: MLN8237 shows >200-fold higher selectivity for Aurora A than the structurally related Aurora B with an IC50 of 396.5 nM, and does not have any significant activity against 205 other kinases. MLN8237 (0.5 μM) treatment inhibits the phosphorylation of Aurora A in MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. MLN8237 significantly inhibits cell proliferation in multiple myeloma (MM) cell lines with IC50 values of 0.003-1.71 μM. MLN8237 displays more potent anti-proliferation activity against primary MM cells and MM cell lines in the presence of BM stroma cells, as well as IL-6 and IGF-1 than against MM cells alone. MLN8237 (0.5 μM) induces 2- to 6-fold increase in G2/M phase in primary MM cells and cell lines, as well as significant apoptosis and senescence, involving the up-regulation of p53, p21 and p27, as well as PARP, caspase 3, and caspase 9 cleavage. In addition, MLN8237 shows strong synergistic anti-MM effect with dexamethasone, as well as additive effect with doxorubicin and bortezomib. MLN8237 (0.5 μM) treatment causes the inhibition of colony formation of FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, and induces a significant increase in the percentage of polyploid cells, and subsequently an increase in the percentage of cells in the sub-G1 phase, which can be further enhanced in combination with cisplatin (2.5 μM), involving the higher induction of TAp73β, PUMA, NOXA, cleaved caspase-3, and cleaved PARP as compared with a single-agent treatment.. Kinase Assay: Aurora A radioactive Flashplate enzyme assay is conducted to determine the nature and degree of MLN8237-mediated inhibition in vitro. Recombinant Aurora A is expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A is conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) is assayed in 50 mM Hepes (pH 7.5), 10 mM MgCl2, 5 mM DTT, 0.05% Tween 20, 2 μM peptide substrate, 3.3 μCi/mL [γ-33P]ATP at 2 μM, and increasing concentrations of MLN8237 by using Image FlashPlates. Cell Assay: Cells are exposed to various concentrations of MLN8237 for 24, 48, and 72 hours. Cells viability is measured using MTT assay, and cell proliferation is measured using 3[H]-thymidine incorporation. For cell cycle analysis, cells are permeabilized by 70% ethanol at -20 °C, and incubated with 50 μg/mL PI and 20 units/mL RNase-A. DNA content is analyzed by flow cytometry using BDFACS-Canto II and FlowJo software. For the detection of apoptosis and senescence, cells are stained with fluorescein isothiocyanate-annexin V and PI. Apoptotic cells are determined by flow cytometric analysis using BDFACS-Canto II and FlowJo software. |
|---|---|
| In Vivo | MLN8237 significantly reduces the tumor burden with tumor growth inhibition (TGI) of 42% and 80% at 15 mg/kg and 30 mg/kg, respectively, and prolongs the survival of mice compared with the control. |
| Animal model | Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells |
| Formulation & Dosage | Dissolved in 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate; 30 mg/kg; Oral gavage |
| References | Blood. 2010 Jun 24;115(25):5202-13; Clin Cancer Res. 2011 Dec 15;17(24):7614-24; Mol Cancer Ther. 2012 Mar;11(3):763-74. |