MLN-8237
MLN-8237 Basic information
- Product Name:
- MLN-8237
- Synonyms:
-
- Benzoic acid, 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxy-
- MLN-8237 4-[[9-Chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid
- alisertib (auroura A kinase inhibitor)
- Fluorocyclopentenylcytosine
- ALISERTIB (MLN8237);MLN 8237; MLN8237;MLN-8237
- 4-((9-Chloro-7-(2-fluoro-6-methoxyphenyl)-5H-benzo[c]pyrimido-[4,5-e]azepin-2-yl)amino)-2-meth
- MLN-823
- MLN-8237
- CAS:
- 1028486-01-2
- MF:
- C27H20ClFN4O4
- MW:
- 518.92
- EINECS:
- 1592732-453-0
- Product Categories:
-
- Inhibitor
- Inhibitors
- Intermediates & Fine Chemicals
- Pharmaceuticals
- API
- Mol File:
- 1028486-01-2.mol
MLN-8237 Chemical Properties
- Boiling point:
- 729.1±70.0 °C(Predicted)
- Density
- 1.43±0.1 g/cm3(Predicted)
- storage temp.
- -20°C
- solubility
- Soluble in DMSO (up to 5 mg/ml)
- form
- solid
- pka
- 4.07±0.10(Predicted)
- color
- Off-white
- Stability:
- Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
MLN-8237 Usage And Synthesis
Description
Alisertib (MLN8237) is a selective 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. Phase 3.
In vitro
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. [1] 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.
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.
Description
Alisertib (MLN8237, 1028486-01-2) is a highly selective and potent (IC50?= 1 nM) cell permeable inhibitor of Aurora A with off-target binding at GABAA?(IC50?= 490 nM).1?It disrupts the Aurora A-Myc complex leading to Myc degradation2?in Myc amplified neuroblastomas3?and p53-mutant human hepatocellular carcinoma cell4. Alisertib has been found to induce apoptosis and autophagy in breast cancer5?and melanoma6?cells?via?suppression of activation of the p38 MAPK pathway.
Chemical Properties
Off-White Solid
Uses
An Aurora kinase inhibitor, used to treat patients with advanced solid tumors.
Definition
ChEBI: 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid is a benzazepine.
target
Aurora A
References
1) Sells?et al.?(2015),?MLN8054 and Alisertib (MLN8237):Discovery of Selective Oral Aurora A Inhibitors; ACS Med. Chem. Lett.?6?630 2) Richards?et al.?(2016),?Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors; Proc. Natl. Acad. Sci. USA?113?13726 3) Brockmann?et al.?(2013),?Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma; Cancer Cell?24?75 4) Dauch?et al.?(2016),?A MYC-aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer; Nat. Med.?22?744 5) Li?et al.?(2015),?The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells; Drug Des. Devel. Ther.?16?1627 6) Shang?et al.?(2017),?Alisertib promotes apoptosis and autophagy in melanoma through p38 MAPK-mediated aurora a signaling; Oncotarget?8?107076
MLN-8237Supplier
- Tel
- 15238060619
- liucunjiang_11@163.com
- Products Intro
- Product Name:Alisertib
CAS:1028486-01-2
Purity:99% Package:1g;5g;10g
- Tel
- sales@boylechem.com
- Products Intro
- Product Name:MLN-8237
CAS:1028486-01-2
- Tel
- 010-82848833 400-666-7788
- jkinfo@jkchemical.com
- Products Intro
- Product Name:MLN 8237 (Contain 10% DMSO)
CAS:1028486-01-2
Package:50Mg,5Mg
- Tel
- +86-21-20908456
- sales@BioChemBest.com
- Products Intro
- Product Name:Alisertib (MLN 8237)
CAS:1028486-01-2
Purity:98%+ Package:50mg;100mg;500mg;1g;5g;10g Remarks:C15972
- Tel
- 13817811078
- sales@jingyan-chemical.com
- Products Intro
- Product Name:MLN8237
Purity:98%