Alisertib - CAS 1028486-01-2
Not Intended for Therapeutic Use. For research use only.
Category:
Inhibitor
Product Name:
Alisertib
Catalog Number:
1028486-01-2
Synonyms:
MLN-8237; Benzoic acid, 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxy-.
CAS Number:
1028486-01-2
Description:
MLN8237 is a second-generation, orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. Aurora kinase inhibitor MLN8237 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.
COA:
Inquire
MSDS:
Inquire
Targets:
Aurora Kinase
Current Developer:
Millennium Pharmaceuticals, Inc.
Chemical Structure
CAS 1028486-01-2 Alisertib

Related Aurora Kinase Products


CAS 885325-71-3 MK-8745

MK-8745
(CAS: 885325-71-3)

MK-8745 is a novel Aurora-A specific inhibitor. MK8745 induced apoptotic cell death in a p53-dependent manner when tested in vitro in cell lines of multiple lin...

CAS 942918-07-2 GSK-1070916A

GSK-1070916A
(CAS: 942918-07-2)

GSK-1070916A is an ATP-competitive inhibitor of the serine/threonine kinases Aurora B and C with potential antineoplastic activity. Aurora B/C kinase inhibitor ...

CAS 1028486-01-2 Alisertib

Alisertib
(CAS: 1028486-01-2)

MLN8237 is a second-generation, orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with pote...

CAS 693228-63-6 CYC116

CYC116
(CAS: 693228-63-6)

CYC116 is a potent inhibitor of Aurora A/B with Ki of 8.0 nM/9.2 nM, is less potent to VEGFR2 (Ki of 44 nM), with 50-fold greater potency than CDKs, not active ...

CAS 898280-07-4 XL228

XL228
(CAS: 898280-07-4)

XL228 is a protein kinase inhibitor targeting IGF1R, the Aurora kinases, FGFR1-3, ABL and SRC family kinases.

CAS 398493-79-3 PHA-680632

PHA-680632
(CAS: 398493-79-3)

PHA-680632 is a is potent inhibitor of Aurora A, Aurora B and Aurora C with IC50 of 27 nM, 135 nM and 120 nM. PHA-680632 is also the first representative of a ...

CAS 1158838-45-9 Aurora A Inhibitor I

Aurora A Inhibitor I
(CAS: 1158838-45-9)

Aurora A Inhibitor I is a novel, potent, and selective inhibitor of Aurora A with IC50 of 3.4 nM. It is 1000-fold more selective for Aurora A than Aurora B.

CAS 331771-20-1 ZM447439

ZM447439
(CAS: 331771-20-1)

ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM, 130 nM respectively, > 8 fold selectivity than Aurora C

CAS 934353-76-1 ENMD-2076

ENMD-2076
(CAS: 934353-76-1)

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has be...

CAS 896466-04-9 AT9283

AT9283
(CAS: 896466-04-9)

AT-9283 is a broad spectrum kinase inhibitor that potently inhibits Aurora A, Aurora B, JAK2, JAK3, and c-ABL (IC50= 3, 3, 1.2, 1.1, and 4 nM, respectively). It...

CAS 722543-31-9 Barasertib

Barasertib
(CAS: 722543-31-9)

Barasertib is an orally bioavailable, small-molecule, dihydrogen phosphate prodrug of the pyrazoloquinazoline Aurora kinase inhibitor AZD1152–hydroxyquinazolin...

CAS 722544-51-6 AZD-1152HQPA

AZD-1152HQPA
(CAS: 722544-51-6)

AZD-1152HQPA is an active metabolite of Barasertib (AZD-1152), which is a novel acetanilide-substituted pyrazole-aminoquinazoline prodrug that is converted rap...

CAS 1095382-05-0 CCT-137690

CCT-137690
(CAS: 1095382-05-0)

CCT137690, an aurora kinase inhibitor CCT137690, is a highly selective, orally bioavailable imidazo[4,5-b]pyridine derivative that inhibits Aurora A and B kinas...

CAS 443797-96-4 JNJ-7706621

JNJ-7706621
(CAS: 443797-96-4)

JNJ-7706621 is a novel cell cycle inhibitor that showed potent inhibition of several cyclin-dependent kinases (CDK) and Aurora kinases and selectively blocked p...

CAS 422513-13-1 Hesperadin

Hesperadin
(CAS: 422513-13-1)

Hesperadin is  an inhibitor of human Aurora B, which can prevent the phosphorylation of substrate with IC(50) of 40 nM. Growth of cultured bloodstream forms was...

CAS 869363-13-3 MLN8054

MLN8054
(CAS: 869363-13-3)

MLN8054 is an aurora kinase inhibitor MLN8054, which is an orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase...

SAR156497
(CAS: 1256137-14-0)

SAR156497 is a selective Aurora A, B and C inhibitor with in vitro and in vivo efficacy IC50 value is 0.5 nM for Aurora A; 1.0 nM for Aurora B (incenp) and 3.0 ...

CAS 1291074-87-7 ENMD-2076 L-(+)-Tartaric acid

ENMD-2076 L-(+)-Tartaric acid
(CAS: 1291074-87-7)

ENMD-2076 L-(+)-Tartaric acid is the tartaric acid of ENMD-2076, selective activity against Aurora A and Flt3 with IC50 of 14 nM and 1.86 nM, 25-fold more selec...

CAS 639089-54-6 Tozasertib

Tozasertib
(CAS: 639089-54-6)

The Aurora kinases (A, B, and C) are a family of serine-threonine kinases that regulate various stages of mitotic function. With significant roles in cell cycle...

CAS 1010085-13-8 MK-5198

MK-5198
(CAS: 1010085-13-8)

MK-5108 is a novel small molecule with potent inhibitory activity against Aurora-A kinase. Although most of the Aurora-kinase inhibitors target both Aurora-A an...

Reference Reading


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.