Alisertib

Size	Price	Stock	Quantity
100 mg	$459	In stock

Purity

0.98

Appearance

Light yellow to yellow Solid

IUPACName

4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid

Synonyms

MLN8237; MLN-8237; MLN 8237; alisertib. Benzoic acid, 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxy-.

InChI Key

ZLHFILGSQDJULK-UHFFFAOYSA-N

InChI

InChI=1S/C27H20ClFN4O4/c1-36-21-5-3-4-20(29)23(21)25-19-10-15(28)6-8-17(19)24-14(12-30-25)13-31-27(33-24)32-16-7-9-18(26(34)35)22(11-16)37-2/h3-11,13H,12H2,1-2H3,(H,34,35)(H,31,32,33)

Canonical SMILES

COC1=C(C(=CC=C1)F)C2=NCC3=CN=C(N=C3C4=C2C=C(C=C4)Cl)NC5=CC(=C(C=C5)C(=O)O)OC

1.Alisertib Combined with Chemotherapy Achieves Response in Neuroblastoma.

Cancer Discov. 2016 Apr;6(4):339. doi: 10.1158/2159-8290.CD-RW2016-035. Epub 2016 Feb 25.

Aurora A kinase inhibition combined with chemotherapy is tolerable in neuroblastoma.

2.MLN-8237: A dual inhibitor of aurora A and B in soft tissue sarcomas.

Nair JS1, Schwartz GK1. Oncotarget. 2016 Mar 15;7(11):12893-903. doi: 10.18632/oncotarget.7335.

Aurora kinases have become an attractive target in cancer therapy due to their deregulated expression in human tumors. Liposarcoma, a type of soft tissue sarcoma in adults, account for approximately 20% of all adult soft tissue sarcomas. There are no effective chemotherapies for majority of these tumors. Efforts made to define the molecular basis of liposarcomas lead to the finding that besides the amplifications of CDK4 and MDM2, Aurora Kinase A, also was shown to be overexpressed. Based on these as well as mathematic modeling, we have carried out a successful preclinical study using CDK4 and IGF1R inhibitors in liposarcoma. MLN8237 has been shown to be a potent and selective inhibitor of Aurora A. MLN-8237, as per our results, induces a differential inhibition of Aurora A and B in a dose dependent manner. At a low nanomolar dose, cellular effects such as induction of phospho-Histone H3 (Ser10) mimicked as that of the inhibition of Aurora kinase A followed by apoptosis.

3.A SILAC-based proteomics elicits the molecular interactome of alisertib (MLN8237) in human erythroleukemia K562 cells.

Shu LP1, Zhou ZW2, Zi D1, He ZX3, Zhou SF2. Am J Transl Res. 2015 Nov 15;7(11):2442-61. eCollection 2015.

Alisertib (MLN8237, ALS), an Aurora kinase A (AURKA) inhibitor, exerts potent anti-tumor effects in the treatment of solid tumor and hematologic malignancies in preclinical and clinical studies. However, the fully spectrum of molecular targets of ALS and its anticancer effect in the treatment of chronic myeloid leukemia (CML) are not clear. This study aimed to examine the proteomic responses to ALS treatment and unveil the molecular interactome and possible mechanisms for its anticancer effect in K562 cells using stable-isotope labeling by amino acids in cell culture (SILAC) approach. The proteomic data identified that ALS treatment modulated the expression of 1541 protein molecules (570 up; 971 down). The pathway analysis showed that 299 signaling pathways and 459 cellular functional proteins directly responded to ALS treatment in K562 cells. These targeted molecules and signaling pathways were mainly involved in cell growth and proliferation, cell metabolism, and cell survival and death.

4.An open-label, single-arm, phase 2 study of the Aurora kinase A inhibitor alisertib in patients with advanced urothelial cancer.

Necchi A1, Lo Vullo S2, Mariani L2, Raggi D3, Giannatempo P3, Calareso G4, Togliardi E5, Crippa F6, Di Genova N7, Perrone F8, Colecchia M8, Paolini B8, Pelosi G8,9, Nicolai N10, Procopio G3, Salvioni R10, De Braud FG3,9. Invest New Drugs. 2016 Apr;34(2):236-42. doi: 10.1007/s10637-016-0328-9. Epub 2016 Feb 12.

Background Progress in developing effective salvage therapies for UC is warranted. Alisertib is an orally available, selective inhibitor of the aurora kinase A. Methods A single-group, phase 2 trial was conducted with alisertib 50 mg orally BID for 7 days, with 14d rest until disease progression (PD) (NCT02109328). The primary endpoint (EP) was RECIST 1.1 objective response-rate (ORR, H0 ≤ 5 %, H1 ≥ 20 %, α = 10 % and β = 20 %). Eligibility included failure of at least one platinum-based regimen. Results From 10/2014 to 04/2015, 22 patients were enrolled (20 evaluable for response), 8 (36.4 %) in second-line and 14 (63.6 %) beyond the second-line. Eight (36.4 %) had an ECOG-performance status 1-2. Two partial responses (PR, ORR: 9.1 %), 7 stable disease (SD) and 11 PD were obtained. Median follow-up was 8.3 months (IQR: 7-10.3), 6-month progression-free survival (PFS) was 13.6 % (95%CI: 4.8-39.0). Two SD are still receiving treatment after 11.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	1.9271 mL	9.6354 mL	19.2708 mL
5 mM	0.3854 mL	1.9271 mL	3.8542 mL
10 mM	0.1927 mL	0.9635 mL	1.9271 mL
50 mM	0.0385 mL	0.1927 mL	0.3854 mL

HPLC

HNMR

I want to purchase Alisertib. And how does Alisertib arrest PANC-1 and BxPC-3 cells in G2/M phase?

Alisertib remarkably arrested PANC-1 and BxPC-3 cells in G2/M phase via regulating the expression of cyclin-dependent kinases 1 and 2, cyclin B1, cyclin D1, p21 Waf1/Cip1, p27 Kip1, and p53.

27/9/2018

Dear Sir, please give information about how Alisertib induces apoptosis and autophagy?

Alisertib induces apoptosis and autophagy through targeting the AKT/mTOR/AMPK/p38 pathway in leukemic cells. Antitumor activity.

3/3/2019

What is the mechanism of action of Alisertib?

Alisertib binds to and inhibits Aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cell proliferation.

25/10/2020

What is the IC50 value of Alisertib?

Alisertib significantly inhibited cell proliferation in multiple myeloma ( MM ) cell lines with IC50 of 0.003-1.71 μM.

11/8/2021

Good afternoon! And how does Alisertib lead the MM cells to mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation?

Alisertib leads the MM cells to mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation through apoptosis and senescence.

18/10/2023

up-regulate p53 and tumor suppressor genes p21 and p27

In my research, Alisertib performed well at up-regulating p53 and tumor suppressor genes p21 and p27.

11/5/2016

inhibit cell proliferation

In our project, Alisertib does well in inhibiting cell proliferation with IC50s ranging from 15 to 469 nM in different tumer cell lines.

21/9/2017

reduce tumor burden

Our study showed that Alisertib can significantly reduce tumor burden and increases overall survival in xenograft-murine model of human-MM. Great performance.

23/1/2018

high selectivity

The selectivity of Alisertibagainst Aurora A was more than 200 times higher than that of Aurora B, and the IC50 was 396.5 nM, while it had no significant activity against 205 other kinases.

23/6/2018

Inducing autophagy in cells

We used cell experiments to give 0.1μmol / L Alisertib, 1μmol / L Alisertib and control drugs. The results showed that Alisertib ( ALS ) increased the autophagy rate of Caco-2 cells compared with the control group, 26.4 % and 26.8 %, respectively, suggesting that ALS induced autophagy in Caco-2 cells.

13/4/2019

antineoplastic activity

Through previous cell experiments, we found that Aliertib induces apoptosis and autophagy by targeting the AKT/mTOR/AMPK/p38 pathway in leukemia cells, and has anti-tumor activity.

28/11/2022

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂