Basic information Description In vitro In vivo Safety Supplier Related
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MLN-8237

Basic information Description In vitro In vivo Safety Supplier Related

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
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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.
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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

Zhengzhou Jingjiang Chemical Co. LTD Gold
Tel
15238060619
Email
liucunjiang_11@163.com
Products Intro
Product Name:Alisertib
CAS:1028486-01-2
Purity:99% Package:1g;5g;10g
Shanghai Boyle Chemical Co., Ltd.
Tel
Email
sales@boylechem.com
Products Intro
Product Name:MLN-8237
CAS:1028486-01-2
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Email
jkinfo@jkchemical.com
Products Intro
Product Name:MLN 8237 (Contain 10% DMSO)
CAS:1028486-01-2
Package:50Mg,5Mg
Chembest Research Laboratories Limited
Tel
+86-21-20908456
Email
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
JinYan Chemicals(ShangHai) Co.,Ltd.
Tel
13817811078
Email
sales@jingyan-chemical.com
Products Intro
Product Name:MLN8237
Purity:98%