Alisertib (MLN8237)

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. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3.

CAS No. 1028486-01-2

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
50mg	JPY 100500	国内在庫あり
200mg	JPY 265500	国内在庫あり
1g	JPY 748500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（338）

製品安全説明書

現在のバッチを見る：純度： 99.64%

99.64

Alisertib (MLN8237)と併用されることが多い化合物

Barasertib (AZD1152-HQPA)

Alisertib and Barasertib strongly inhibit the growth and proliferation of AML cells.

Qi J, et al. Biomed Pharmacother. 2019 Sep;117:109113.

Volasertib

Alisertib and Volasertib inhibit AURKA and PLK1 and synergistically block cell cycle progression in diffuse midline glioma cells.

Metselaar DS, et al. iScience. 2022 May 13;25(6):104398.

Lenvatinib

Alisertib and Lenvatinib significantly enhance the suppression of tumor growth and induce apoptosis in nude mice.

Hao J, et al. Biomed Res Int. 2021; 2021: 6613439.

Irinotecan

Alisertib and Irinotecan along with temozolomide show antitumor activity in patients with MYCN nonamplified tumors.

DuBois SG, et al.Clin Cancer Res. 2018 Dec 15;24(24):6142-6149.

Paclitaxel

Alisertib and Paclitaxel give additive and synergistic antitumor effects in xenograft models of triple-negative breast cancer.

Falchook G, et al. JAMA Oncol. 2019 Jan; 5(1): e183773.

Alisertib (MLN8237)関連製品

関連ターゲット	Aurora A Aurora B Aurora C Aurora B	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

Aurora Kinaseシグナル伝達経路

Aurora Kinase阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
OE33	Cytotoxic Assay	0.5 μM	24 h	Decreases cell survival	22972611
FLO-1	Cytotoxic Assay	0.5 μM	24 h	Decreases cell survival	22972611
AGS	Cytotoxic Assay	0.5 μM	24 h	Decreases cell survival	22972611
TIB-48	Cytotoxic Assay	1 μM	48 h	Induces apoptosis	23153524
CRL-2396	Cytotoxic Assay	1 μM	48 h	Induces apoptosis	23153524
2885	Growth Inhibition Assay	100 μM	72 h	Attenuates cell growth	23328114
2884	Growth Inhibition Assay	100 μM	72 h	Attenuates cell growth	23328114
S462	Growth Inhibition Assay	100 μM	72 h	Attenuates cell growth	23328114
UM-UC-3	Apoptosis Assay	3.16 μM	96 h	IC50=0.0449 μM	23403633
RT4	Apoptosis Assay	3.16 μM	96 h	IC50=0.1198 μM	23403633
T24	Apoptosis Assay	3.16 μM	96 h	IC50=0.0306 μM	23403633
UM-UC-3	Function Assay	1 μM	48 h	Induces cell cycle arrest	23403633
RT4	Function Assay	1 μM	48 h	Induces cell cycle arrest	23403633
T24	Function Assay	1 μM	48 h	Induces cell cycle arrest	23403633
GB169	Growth Inhibition Assay	1 μM	7 d	IC50=0.032 μM	25106428
GB9	Growth Inhibition Assay	1 μM	7 d	IC50=0.024 μM	25106428
GB30	Growth Inhibition Assay	1 μM	7 d	IC50=0.011 μM	25106428
HSC-3	Growth Inhibition Assay	1 μM	48 h	IC50=0.54 μM	25366143
NCI-N78	Function Assay	5 μM	24 h	Induces the autophagy	25609923
AGS	Function Assay	5 μM	24 h	Induces the autophagy	25609923
NCI-N78	Apoptosis Assay	5 μM	24 h	Induces apoptosis	25609923
AGS	Apoptosis Assay	5 μM	24 h	Induces apoptosis	25609923
NCI-N78	Growth Inhibition Assay	25 μM	24 h	IC50=26.33 μM	25609923
AGS	Growth Inhibition Assay	25 μM	24 h	IC50=19.09 μM	25609923
OVCAR4	Apoptosis Assay	5 μM	24 h	Induces apoptosis	25624750
SKOV3	Apoptosis Assay	5 μM	24 h	Induces apoptosis	25624750
OVCAR4	Function Assay	5 μM	72 h	Induces G2/M arrest	25624750
SKOV3	Function Assay	5 μM	72 h	Induces G2/M arrest	25624750
OVCAR4	Growth Inhibition Assay	100 μM	24 h	IC50=22.13 μM	25624750
SKOV3	Growth Inhibition Assay	100 μM	24 h	IC50=20.48 μM	25624750
BxPC-3	Function Assay	5 μM	24 h	Induces autophagic cell death	25632225
PANC-1	Function Assay	5 μM	24 h	Induces autophagic cell death	25632225
BxPC-3	Function Assay	5 μM	24 h	Induces cell cycle arrest in G2/M phase	25632225
PANC-1	Function Assay	5 μM	24 h	Induces cell cycle arrest in G2/M phase	25632225
BxPC-3	Growth Inhibition Assay	50 μM	24 h	IC50=6.8 μM	25632225
PANC-1	Growth Inhibition Assay	50 μM	24 h	IC50=7.1 μM	25632225
MG-63	Function Assay	5 μM	24 h	Promotes autophagic cell death	25792811
U-2 OS	Function Assay	5 μM	24 h	Promotes autophagic cell death	25792811
MG-63	Apoptosis Assay	5 μM	24 h	Induces apoptotic cell death	25792811
U-2 OS	Apoptosis Assay	5 μM	24 h	Induces apoptotic cell death	25792811
MG-63	Growth Inhibition Assay	50 μM	24 h	IC50=9.5 μM	25792811
U-2 OS	Growth Inhibition Assay	50 μM	24 h	IC50=16.6 μM	25792811
MDA-MB-231	Function Assay	1 μM	72 h	Induces autophagic death	25834401
MCF7	Function Assay	1 μM	72 h	Induces autophagic death	25834401
MDA-MB-231	Apoptosis Assay	5 μM	24 h	Induces apoptotic death	25834401
MCF7	Apoptosis Assay	5 μM	24 h	Induces apoptotic death	25834401
MDA-MB-231	Function Assay	5 μM	24 h	Increases the expression level of p53	25834401
MDA-MB-231	Function Assay	5 μM	24 h	Increases the expression level of p27 Kip1	25834401
MDA-MB-231	Function Assay	5 μM	24 h	Increases the expression level of p21 Waf1/Cip1	25834401
MDA-MB-231	Function Assay	5 μM	24 h	Decreases the expression level of cyclin B1	25834401
MDA-MB-231	Function Assay	1 μM	24 h	Increases the expression level of CDK2	25834401
MDA-MB-231	Function Assay	5 μM	24 h	Decreases the expression level of CDK1/CDC2	25834401
MCF7	Function Assay	5 μM	24 h	Increases the expression level of p27 Kip1	25834401
MCF7	Function Assay	5 μM	24 h	Increases the expression level of p21 Waf1/Cip1	25834401
MCF7	Function Assay	5 μM	24 h	Decreases the expression level of cyclin B1	25834401
MCF7	Function Assay	5 μM	24 h	Decreases the expression level of CDK2	25834401
MCF7	Function Assay	5 μM	24 h	Decreases the expression level of CDK1/CDC2	25834401
MDA-MB-231	Function Assay	5 μM	24 h	Induces G3/M arrest	25834401
MCF7	Function Assay	5 μM	24 h	Induces G2/M arrest	25834401
SNU1544	Growth Inhibition Assay	0.5 μM	72 h	IC50=1 μM	26136684
MIP-101	Growth Inhibition Assay	0.5 μM	72 h	IC50=1 μM	26136684
DLD-1	Growth Inhibition Assay	0.5 μM	72 h	IC50<0.8 μM	26136684
HCT15	Growth Inhibition Assay	0.5 μM	72 h	IC50<0.4 μM	26136684
SW948	Growth Inhibition Assay	0.5 μM	72 h	IC50=1 μM	26136684
LS180	Growth Inhibition Assay	0.5 μM	72 h	IC50=1 μM	26136684
T84	Growth Inhibition Assay	0.5 μM	72 h	IC50=0.09 μM	26136684
LS174T	Growth Inhibition Assay	0.5 μM	72 h	IC50=0.05 μM	26136684
HCT116	Growth Inhibition Assay	0.5 μM	72 h	IC50=0.04 μM	26136684
SKLMS	Cytotoxic Assay	75 nM	96 h	Induces apoptosis	22821997
Leio285	Cytotoxic Assay	75 nM	96 h	Induces apoptosis	22821997
Mes-Sa	Cytotoxic Assay	75 nM	96 h	Induces apoptosis	22821997
DAOY	Cytotoxic Assay	10 μM	72 h	IC50=0.04 μM	22669335
IMR32	Cytotoxic Assay	10 μM	72 h	IC50=0.03 μM	22669335
Molt-4	Cytotoxic Assay	10 μM	72 h	IC50=0.02 μM	22669335
MOLM-13	Growth Inhibition Assay	3 μM	72 h	Diminishes cell viability	22488249
HL-60	Growth Inhibition Assay	3 μM	72 h	Diminishes cell viability	22488249
MV4-11	Growth Inhibition Assay	3 μM	72 h	Diminishes cell viability	22488249
SKM-1	Growth Inhibition Assay	3 μM	72 h	Diminishes cell viability	22488249
SH2	Growth Inhibition Assay	3 μM	72 h	Diminishes cell viability	22488249
NOMO-1	Growth Inhibition Assay	3 μM	72 h	Diminishes cell viability	22488249
OCL-AML2	Growth Inhibition Assay	3 μM	72 h	Diminishes cell viability	22488249
PL-21	Growth Inhibition Assay	3 μM	72 h	Diminishes cell viability	22488249
KG-1	Growth Inhibition Assay	3 μM	72 h	Diminishes cell viability	22488249
A172	Cytotoxic Assay	100 μM	24 h	IC50=0.120 μM	22274399
U87	Cytotoxic Assay	100 μM	24 h	IC50=0.105 μM	22274399
U251	Cytotoxic Assay	100 μM	24 h	IC50=0.100 μM	22274399
T98	Cytotoxic Assay	100 μM	24 h	IC50=0.125 μM	22274399
LN18	Cytotoxic Assay	100 μM	24 h	IC50=0.210 μM	22274399
LN443	Cytotoxic Assay	100 μM	24 h	IC50=0.220 μM	22274399
HF66	Cytotoxic Assay	100 μM	24 h	IC50=0.225 μM	22274399
HF2303	Cytotoxic Assay	100 μM	24 h	IC50=0.060 μM	22274399
HF2359	Cytotoxic Assay	100 μM	24 h	IC50=0.060 μM	22274399
HF2414	Cytotoxic Assay	100 μM	24 h	IC50=0.080 μM	22274399
A-673	Growth Inhibition Assay	10 μM	96 h	IC50=0.032 μM	21448591
TC-32	Growth Inhibition Assay	10 μM	96 h	IC50=0.039 μM	21448591
TC-71	Growth Inhibition Assay	10 μM	96 h	IC50=0.102 μM	21448591
SK-N-MC	Growth Inhibition Assay	10 μM	96 h	IC50=0.072 μM	21448591
CHLA-9	Growth Inhibition Assay	10 μM	96 h	IC50=0.018 μM	21448591
CHLA-10	Growth Inhibition Assay	10 μM	96 h	IC50=0.060 μM	21448591
CHLA-25	Growth Inhibition Assay	10 μM	96 h	IC50=0.168 μM	21448591
CHLA-32	Growth Inhibition Assay	10 μM	96 h	IC50=0.136 μM	21448591
CHLA-56	Growth Inhibition Assay	10 μM	96 h	IC50=10 μM	21448591
CHLA-258	Growth Inhibition Assay	10 μM	96 h	IC50=0.132 μM	21448591
COG-E-352	Growth Inhibition Assay	10 μM	96 h	IC50=0.043 μM	21448591
CHLA-90	Growth Inhibition Assay	10 μM	96 h	IC50=0.061 μM	21448591
CHLA-119	Growth Inhibition Assay	10 μM	96 h	IC50=0.022 μM	21448591
CHLA-122	Growth Inhibition Assay	10 μM	96 h	IC50=0.019 μM	21448591
CHLA-136	Growth Inhibition Assay	10 μM	96 h	IC50=0.039 μM	21448591
CHLA-140	Growth Inhibition Assay	10 μM	96 h	IC50=0.026 μM	21448591
LA-N-6	Growth Inhibition Assay	10 μM	96 h	IC50=0.054 μM	21448591
NB-1643	Growth Inhibition Assay	10 μM	96 h	IC50=0.037 μM	21448591
NB-EBc1	Growth Inhibition Assay	10 μM	96 h	IC50=0.050 μM	21448591
SK-N-BE-1	Growth Inhibition Assay	10 μM	96 h	IC50=0.028 μM	21448591
SK-N-BE-2	Growth Inhibition Assay	10 μM	96 h	IC50=0.036 μM	21448591
SMS-KAN	Growth Inhibition Assay	10 μM	96 h	IC50=0.034 μM	21448591
SMS-KANR	Growth Inhibition Assay	10 μM	96 h	IC50=0.026 μM	21448591
SMS-KCN	Growth Inhibition Assay	10 μM	96 h	IC50=0.019 μM	21448591
SMS-KCNR	Growth Inhibition Assay	10 μM	96 h	IC50=0.010 μM	21448591
SMS-LHN	Growth Inhibition Assay	10 μM	96 h	IC50=0.032 μM	21448591
SMS-MSN	Growth Inhibition Assay	10 μM	96 h	IC50=0.022 μM	21448591
SMS-SAN	Growth Inhibition Assay	10 μM	96 h	IC50=0.020 μM	21448591
Granta-4	Cytotoxic Assay	10 μM	7 d	IC50=0.040 μM	21291867
DB	Cytotoxic Assay	10 μM	7 d	IC50=0.042 μM	21291867
RL	Cytotoxic Assay	10 μM	7 d	IC50=0.015 μM	21291867
K562	Growth Inhibition Assay	10 μM	96 h	IC50=0.087 μM	21091633
LAMA-84	Growth Inhibition Assay	10 μM	96 h	IC50=0.057 μM	21091633
MM15	Growth Inhibition Assay	4 μM	72 h	IC50=0.13 μM	20382844
OPM1	Growth Inhibition Assay	4 μM	72 h	IC50=0.03 μM	20382844
RPM1	Growth Inhibition Assay	4 μM	72 h	IC50=10.32 μM	20382844
INA6	Growth Inhibition Assay	4 μM	72 h	IC50=0.002 μM	20382844
OPM2	Growth Inhibition Assay	4 μM	72 h	IC50=4.37 μM	20382844
MM1R	Growth Inhibition Assay	4 μM	72 h	IC50=1.68 μM	20382844
DOX40	Growth Inhibition Assay	4 μM	72 h	IC50=5.48 μM	20382844
LR5	Growth Inhibition Assay	4 μM	72 h	IC50=2.53 μM	20382844
U266	Growth Inhibition Assay	4 μM	72 h	IC50=1.43 μM	20382844
RD	Growth Inhibition Assay	10 μM	96 h	IC50=0.228 μM	20108338
Rh41	Growth Inhibition Assay	10 μM	96 h	IC50=0.090 μM	20108338
Rh30	Growth Inhibition Assay	10 μM	96 h	IC50=0.230 μM	20108338
BT-12	Growth Inhibition Assay	10 μM	96 h	IC50=0.060 μM	20108338
CHLA-266	Growth Inhibition Assay	10 μM	96 h	IC50=0.072 μM	20108338
TC-71	Growth Inhibition Assay	10 μM	96 h	IC50=0.102 μM	20108338
SJ-GBM2	Growth Inhibition Assay	10 μM	96 h	IC50=0.050 μM	20108338
NALM-6	Growth Inhibition Assay	10 μM	96 h	IC50=0.062 μM	20108338
COG-LL-317	Growth Inhibition Assay	10 μM	96 h	IC50=0.047 μM	20108338
RS4-11	Growth Inhibition Assay	10 μM	96 h	IC50=0.018 μM	20108338
MOLT-4	Growth Inhibition Assay	10 μM	96 h	IC50=0.026 μM	20108338
CCRF-CEM	Growth Inhibition Assay	10 μM	96 h	IC50=0.094 μM	20108338
Kasumi-1	Growth Inhibition Assay	10 μM	96 h	IC50=0.103 μM	20108338
Karpas-299	Growth Inhibition Assay	10 μM	96 h	IC50=0.038 μM	20108338
Ramos-RA1	Growth Inhibition Assay	10 μM	96 h	IC50=0.127 μM	20108338
Calu6	Antitumor assay	20 mg/kg	21 days	Antitumor activity against human Calu6 cells xenografted in mouse assessed as tumor growth inhibition at 20 mg/kg, po bid administered for 21 days	26101564
HeLa Kyoto	Function assay	0.25 uM	20 hrs	Inhibition of Aurora A kinase localization at spindle microtubules in human HeLa Kyoto cells at 0.25 uM incubated for 20 hrs	27391133
MDA-MB-231	Function assay	1 uM	48 hrs	Induction of chromosome alignment defects in human MDA-MB-231 cells at 1 uM after 48 hrs by DAPI staining based immunofluorescence assay	29358147
MDA-MB-231	Function assay	1 uM	48 hrs	Induction of aberrant spindle formation with tripolar and tetrapolar occurrence in human MDA-MB-231 cells at 1 uM after 48 hrs by DAPI staining based immunofluorescence assay	29358147
MDA-MB-231	Function assay	0.5 uM	48 hrs	Inhibition of alpha-tubulin in human MDA-MB-231 cells assessed as abolishment of regular location of protein at 0.5 uM after 48 hrs by DAPI staining based immunofluorescence assay	29358147
MDA-MB-231	Function assay	0.5 uM	48 hrs	Inhibition of AURKA in human MDA-MB-231 cells assessed as abolishment of regular location of protein at 0.5 uM after 48 hrs by DAPI staining based immunofluorescence assay	29358147
TIB-48	Growth Inhibition Assay	100 μM		IC50=0.088 μM	23153524
CRL-2396	Growth Inhibition Assay	100 μM		IC50=0.092 μM	23153524
SKOV3ip2	Function Assay	50 nM		Inhibits cell migration	23334327
OVCAR-5	Function Assay	50 nM		Inhibits cell migration	23334327
Tib 152	Cytotoxic Assay		72 h	IC50=0.8 μM	25878331
Sup-T1	Cytotoxic Assay		72 h	IC50=2.142 μM	25878331
J.Cam 1.6	Cytotoxic Assay		72 h	IC50=0.105 μM	25878331
CCL119	Cytotoxic Assay		72 h	IC50=0.062 μM	25878331
DND41	Cytotoxic Assay		72 h	IC50=0.1 μM	25878331
HH	Cytotoxic Assay		72 h	IC50=0.7 μM	25878331
H9	Cytotoxic Assay		72 h	IC50=0.6 μM	25878331
Z-138	Cytotoxic Assay		72 h	IC50=0.013 μM	25878331
Rec-1	Cytotoxic Assay		72 h	IC50=0.087 μM	25878331
JVM-2	Cytotoxic Assay		72 h	IC50=0.01 μM	25878331
Jeko-1	Cytotoxic Assay		72 h	IC50=0.029 μM	25878331
SU-DHL6	Cytotoxic Assay		72 h	IC50=0.482 μM	25878331
OCI-LY7	Cytotoxic Assay		72 h	IC50=0.081 μM	25878331
SU-DHL2	Cytotoxic Assay		72 h	IC50=0.01 μM	25878331
OCI-Ly10	Cytotoxic Assay		72 h	IC50=0.058 μM	25878331
GSS	Antiproliferative assay		72 hrs	Antiproliferative activity against human GSS cells after 72 hrs by WST8 assay, IC50 = 0.039 μM.	25625617
LU99A	Antiproliferative assay		72 hrs	Antiproliferative activity against human LU99A cells after 72 hrs by WST8 assay, IC50 = 0.062 μM.	25625617
HL60	Antiproliferative assay		72 hrs	Antiproliferative activity against human HL60 cells after 72 hrs by WST8 assay, IC50 = 0.074 μM.	25625617
LC2/ad	Antiproliferative assay		72 hrs	Antiproliferative activity against human LC2/ad cells after 72 hrs by WST8 assay, IC50 = 0.077 μM.	25625617
MKN45	Antiproliferative assay		72 hrs	Antiproliferative activity against human MKN45 cells after 72 hrs by WST8 assay, IC50 = 0.093 μM.	25625617
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by WST8 assay, IC50 = 0.095 μM.	25625617
Lu116	Antiproliferative assay		72 hrs	Antiproliferative activity against human Lu116 cells after 72 hrs by WST8 assay, IC50 = 0.097 μM.	25625617
NCI-H358	Antiproliferative assay		72 hrs	Antiproliferative activity against human NCI-H358 cells after 72 hrs by WST8 assay, IC50 = 0.1 μM.	25625617
MIAPaCa2	Antiproliferative assay		72 hrs	Antiproliferative activity against human MIAPaCa2 cells after 72 hrs by WST8 assay, IC50 = 0.13 μM.	25625617
PC14	Antiproliferative assay		72 hrs	Antiproliferative activity against human PC14 cells after 72 hrs by WST8 assay, IC50 = 0.17 μM.	25625617
HT-29	Antiproliferative assay		72 hrs	Antiproliferative activity against human HT-29 cells after 72 hrs by WST8 assay, IC50 = 0.33 μM.	25625617
HCT15	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT15 cells after 72 hrs by WST8 assay, IC50 = 0.74 μM.	25625617
BL21 (DE3) Rosetta	Function assay		30 mins	Inhibition of His-tagged human Aurora A kinase (122 to 40 residues) expressed in Escherichia coli BL21 (DE3) Rosetta cells using biotinylated STK2 substrate incubated for 30 mins by HTRF assay, IC50 = 0.00004 μM.	27391133
HeLa Kyoto	Function assay		20 hrs	Inhibition of Aurora B kinase in human HeLa Kyoto cells assessed as effect on distribution of phspho-histone H3 ser10 level incubated for 20 hrs, IC50 = 0.0015 μM.	27391133
HeLa Kyoto	Function assay		20 hrs	Inhibition of Aurora A kinase autophosphorylation at Thr288 in human HeLa Kyoto cells incubated for 20 hrs, IC50 = 0.0067 μM.	27391133
Sf9	Function assay			Competitive inhibition of recombinant mouse aurora kinase A expressed in insect Sf9 cells in presence of ATP, Ki = 0.0003 μM.	26101564
Sf9	Function assay			Inhibition of recombinant mouse aurora kinase A expressed in insect Sf9 cells using biotin-GLRRASLG as substrate in presence of [gamma-33P]ATP, IC50 = 0.001 μM.	26101564
HCT116	Function assay			Inhibition of aurora kinase A autophosphorylation at T288 in human HCT116 cells by immunofluorescence analysis, IC50 = 0.007 μM.	26101564
HCT116	Cytotoxicity assay			Cytotoxicity against human HCT116 cells assessed as inhibition of cell proliferation by BrdU incorporation assay, GI50 = 0.03 μM.	26101564
HCT116	Function assay			Inhibition of aurora kinase B in human HCT116 cells assessed as inhibition of histone H3 phosphorylation by immunofluorescence analysis, IC50 = 1.5 μM.	26101564
multiple myeloma	Function assay			Suppression of cell mitosis in human multiple myeloma cells, IC50 = 0.003 μM.	28918096
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

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. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3.

特性

First orally available inhibitor of Aurora A.

Targets

Aurora A ^[1]
(Cell-free assay)

1.2 nM

In Vitro
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. ^[2] 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. ^[3]
Kinase Assay	Aurora A radioactive Flashplate enzyme assay
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.
細胞実験	細胞株	MM1.S, MM.1R, LR5, RPMI 8226, DOX40, OPM1, OPM2, INA6, and U266
	濃度	Dissolved in DMSO, final concentrations ~10 μM
	反応時間	24, 48, and 72 hours
	実験の流れ	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-AURKA(T288) / p-EIF4E(S209) / c-Myc phospho-Aurora A / Aurora B H3S10P / H3K27me2 / H3K27me3 / H3K9me2 / H3AcK / H4K16Ac		28073841
	Growth inhibition assay	Cell viability		25632225
	Immunofluorescence	acetylated α-tubulin / γ-tubulin E-cadherin / β-catenin / vimentin / p-SMAD5 Centrin-2 / tubulin phospho-Aurora A(T288)		29401581

In Vivo
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. ^[2]
動物実験	動物モデル	Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells
	投与量	~30 mg/kg/day
	投与経路	Orally

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT04479306	Completed	Recurrent Lung Non-Small Cell Carcinoma\|Stage IIIB Lung Cancer AJCC v8\|Stage IV Lung Cancer AJCC v8\|Stage IVA Lung Cancer AJCC v8\|Stage IVB Lung Cancer AJCC v8	M.D. Anderson Cancer Center	June 18 2020	Phase 1
NCT02812056	Withdrawn	Malignant Neoplasms of Digestive Organs\|Malignant Neoplasms of Female Genital Organs\|Malignant Neoplasms of Lip Oral Cavity and Pharynx\|Malignant Neoplasms of Male Genital Organs	M.D. Anderson Cancer Center\|Millennium Pharmaceuticals Inc.	September 2016	Phase 1
NCT02719691	Completed	Metastatic Breast Cancer\|Solid Tumors	University of Colorado Denver	May 13 2016	Phase 1
NCT02367352	Terminated	Advanced Solid Tumors\|Ovarian Cancer\|Small Cell Lung Cancer	Millennium Pharmaceuticals Inc.\|Takeda	March 19 2015	Phase 1

参考
[1] Manfredi MG, et al. Clin Cancer Res, 2011, 17(24), 7614-7624. [2] G?rgün G, et al. Blood, 2010, 115(25), 5202-521 [3] Sehdev V, et al. Mol Cancer Ther, 2012, 11(3), 763-774.

参考

化学情報

分子量	518.92	化学式	C₂₇H₂₀ClFN₄O₄
CAS No.	1028486-01-2	SDF	Download Alisertib (MLN8237) SDFをダウンロードする
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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 50 mg/mL ( (96.35 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):