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Tozasertib (VX-680)

別名: MK-0457 中文名稱(chēng)：陶扎色替

Tozasertib (VX-680)是一種pan-Aurora抑制劑，對(duì)Aurora A作用最強(qiáng)，無(wú)細(xì)胞試驗(yàn)中Kiapp為0.6 nM，而對(duì)Aurora B/Aurora C的作用較弱，對(duì)Aurora A選擇性比其他55種激酶高100倍。唯二的例外是 Fms-related tyrosine kinase-3 (FLT-3) 和 BCR-ABL tyrosine kinase，也可被 Tozasertib 抑制，對(duì)應(yīng)的Ki值均為30 nM和30 nM。Tozasertib 可誘導(dǎo)凋亡和自噬。Phase 2。

Tozasertib (VX-680) Chemical Structure

Tozasertib (VX-680) Chemical Structure

CAS: 639089-54-6

規(guī)格 價(jià)格 庫(kù)存 購(gòu)買(mǎi)數(shù)量
10mM (1mL in DMSO) 1570 現(xiàn)貨
25mg 1211.51 現(xiàn)貨
250mg 3833.09 現(xiàn)貨
1g 15315.69 現(xiàn)貨
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400-668-6834

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Tozasertib (VX-680)相關(guān)產(chǎn)品

相關(guān)信號(hào)通路圖

Aurora Kinase Signaling Pathways

Aurora Kinase信號(hào)通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系 實(shí)驗(yàn)類(lèi)型 給藥濃度 孵育時(shí)間 活性描述 文獻(xiàn)信息
HeLa Function assay 10 to 1000 nM 48 hrs Inhibition of Aurora kinase B in human HeLa cells assessed as delay in mitotic arrest by accumulation of multinucleated cells with 4N/8N DNA content at 10 to 1000 nM after 48 hrs by propidium iodide staining-based FACS flow cytometric analysis 23808327
HCT116 Antitumor assay 50 mg/kg 5 days Antitumor activity against human HCT116 cells xenografted in athymic nu/nu mouse assessed as reduction in tumor size at 50 mg/kg, iv qd for 5 days per week for 2 weeks measured twice a week 23808327
HCT116 Function assay 100 nM 24 hrs Inhibition of cytokinesis in human HCT116 cells at 100 nM after 24 hrs by propidium iodide/RNase staining-based flow cytometric analysis 30143423
HCT116 Function assay 1 uM 24 hrs Inhibition of cytokinesis in human HCT116 cells at 1 uM after 24 hrs by propidium iodide/RNase staining-based flow cytometric analysis 30143423
HCT116 Function assay 1 uM 3 hrs Inhibition of Aurora B in human HCT116 cells assessed as reduction in histone H3 phosphorylation at Ser10 residue up to 1 uM after 3 hrs by Western blot analysis 30143423
HeLa Cell cycle assay 5 uM 12 hrs Cell cycle arrest in human HeLa cells assessed as decrease in cyclin B1 protein expression at 5 uM after 12 hrs by Western blot analysis 30502115
HeLa Cell cycle assay 5 uM 12 hrs Cell cycle arrest in human HeLa cells assessed as decrease in cdc2 protein expression at 5 uM after 12 hrs by Western blot analysis 30502115
HeLa Function assay 5 uM 12 hrs Inhibition of Aurora A phosphorylation at Thr288 residue in human HeLa cells at 5 uM after 12 hrs by Western blot analysis 30502115
HeLa Function assay 5 uM 12 hrs Inhibition of Aurora B phosphorylation at Thr232 residue in human HeLa cells at 5 uM after 12 hrs by Western blot analysis 30502115
HCT15 Cytotoxicity assay 48 hrs Cytotoxicity against human HCT15 cells assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=1.23μM 30143423
HCT116 Cytotoxicity assay 48 hrs Cytotoxicity against human HCT116 cells assessed as reduction in cell viability after 48 hrs by MTT assay, IC50=0.45μM 30143423
L929sA Function assay 24 hrs Inhibition of Aurk mouse L929sA cells transfected with human Fas assessed as increase in nuclear area after 24 hrs in presence of TNF by Hoechst 33342 staining-based microscopic assay, IC50=1.06μM 29437386
L929sA Function assay 24 hrs Inhibition of RIPK1 in mouse L929sA cells transfected with human Fas assessed as inhibition in TNF-induced necroptosis pretreated for 24 hrs followed by TNF and zVAD.fmk addition measured after 3 hrs by Hoechst 33342/propidium iodide staining-based assay, IC50=1.02μM 29437386
L929sA Function assay 0.5 hrs Inhibition of RIPK1 in mouse L929sA cells transfected with human Fas assessed as inhibition in TNF-induced necroptosis pretreated for 0.5 hrs followed by TNF and zVAD.fmk addition measured after 3 hrs by Hoechst 33342/propidium iodide staining-based assay, IC50=0.98μM 29437386
L929sA Function assay 24 hrs Inhibition of Aurk mouse L929sA cells transfected with human Fas assessed as reduction in cell growth after 24 hrs in presence of TNF by Hoechst 33342 staining-based microscopic assay, IC50=0.97μM 29437386
HCT116 Antiproliferative assay 48 hrs Antiproliferative activity against human HCT116 cells after 48 hrs by CCK8 assay, IC50=4.32μM 29358147
HeLa Antiproliferative assay 48 hrs Antiproliferative activity against human HeLa cells after 48 hrs by CCK8 assay, IC50=2.93μM 29358147
MCF7 Antiproliferative assay 48 hrs Antiproliferative activity against human MCF7 cells after 48 hrs by CCK8 assay, IC50=1.3μM 29358147
A431 Antiproliferative assay 48 hrs Antiproliferative activity against human A431 cells after 48 hrs by CCK8 assay, IC50=0.24μM 29358147
MDA-MB-231 Antiproliferative assay 48 hrs Antiproliferative activity against human MDA-MB-231 cells after 48 hrs by CCK8 assay, IC50=0.127μM 29358147
K562 Antiproliferative assay 48 hrs Antiproliferative activity against human K562 cells after 48 hrs by CCK8 assay, IC50=0.079μM 29358147
U937 Antiproliferative assay 48 hrs Antiproliferative activity against human U937 cells after 48 hrs by CCK8 assay, IC50=0.036μM 29358147
HCT8 Cytotoxicity assay 48 hrs Cytotoxicity against human HCT8 cells after 48 hrs by MTT assay, IC50=44.6μM 25812967
HeLa Cytotoxicity assay 48 hrs Cytotoxicity against human HeLa cells after 48 hrs by MTT assay, IC50=27.3μM 25812967
A549 Cytotoxicity assay 48 hrs Cytotoxicity against human A549 cells after 48 hrs by MTT assay, IC50=19.4μM 25812967
HeLa Function assay 12 hrs Inhibition of Aurora B in human HeLa cells after 12 hrs by ELISA method, IC50=0.453μM 25812967
HeLa Function assay 12 hrs Inhibition of Aurora A in human HeLa cells after 12 hrs by ELISA method, IC50=0.261μM 25812967
HepG2 Cytotoxicity assay 48 hrs Cytotoxicity against human HepG2 cells after 48 hrs by MTT assay, TC50=3.3μM 24910766
NCI-N87 Antiproliferative assay 72 hrs Antiproliferative activity against human NCI-N87 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=11.6μM 24681066
SKBR3 Antiproliferative assay 72 hrs Antiproliferative activity against human SKBR3 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=9.99μM 24681066
PC3 Antiproliferative assay 72 hrs Antiproliferative activity against human PC3 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=5.81μM 24681066
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=4.32μM 24681066
PANC1 Antiproliferative assay 72 hrs Antiproliferative activity against human PANC1 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=4.13μM 24681066
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=3.05μM 24681066
HeLa Antiproliferative assay 72 hrs Antiproliferative activity against human HeLa cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=2.93μM 24681066
MCF7 Antiproliferative assay 72 hrs Antiproliferative activity against human MCF7 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=1.3μM 24681066
DU145 Antiproliferative assay 72 hrs Antiproliferative activity against human DU145 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=0.4μM 24681066
A431 Antiproliferative assay 72 hrs Antiproliferative activity against human A431 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=0.24μM 24681066
MDA-MB-231 Antiproliferative assay 72 hrs Antiproliferative activity against human MDA-MB-231 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=0.127μM 24681066
K562 Antiproliferative assay 72 hrs Antiproliferative activity against human K562 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=0.0791μM 24681066
HL60 Antiproliferative assay 72 hrs Antiproliferative activity against human HL60 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=0.0382μM 24681066
U937 Antiproliferative assay 72 hrs Antiproliferative activity against human U937 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=0.036μM 24681066
MOLT4 Antiproliferative assay 72 hrs Antiproliferative activity against human MOLT4 cells assessed as cell viability after 72 hrs by CCK8 assay, IC50=0.0212μM 24681066
HCT116 Antiproliferative assay 96 hrs Antiproliferative activity against human HCT116 cells after 96 hrs by MTS assay, EC50=0.12μM 23808327
sf9 Function assay 15 mins Inhibition of GST-tagged Aurora kinase A catalytic domain (123 to 401 amino acids) (unknown origin) expressed in sf9 cells using tetra(LRRWSLG) as substrate preincubated for 15 mins prior to substrate addition measured after 90 mins by luminescence assay, IC50=0.02μM 23808327
MCF7 Cytotoxicity assay 48 hrs Cytotoxicity against human MCF7 cells after 48 hrs by MTT assay, IC50=0.38μM 22572580
HCT116 Cytotoxicity assay 48 hrs Cytotoxicity against human HCT116 cells after 48 hrs by MTT assay, IC50=0.3μM 22572580
HCT116 Cytotoxicity assay 72 hrs Cytotoxicity against human HCT116 cells assessed as distinct polyploidy phenotype after 72 hrs, Activity=0.03μM 19143567
HCT116 Cytotoxicity assay 10 to 14 days Cytotoxicity against human HCT116 cells assessed as number of colonies after 10 to 14 days by colony forming assay, IC50=0.024μM 19143567
HCT116 Function assay 3 hrs Inhibition of Aurora A phosphorylation at Thr288 residue in human HCT116 cells up to 1 uM after 3 hrs by Western blot analysis 30143423
HCT116 Function assay 3 hrs Inhibition of Aurora B phosphorylation at Thr232 residue in human HCT116 cells up to 1 uM after 3 hrs by Western blot method 30143423
HeLa Function assay 12 hrs Inhibition of Aurora A phosphorylation at Thr288 residue in human HeLa cells after 12 hrs by ELISA, IC50=0.013μM 30502115
HeLa Function assay 12 hrs Inhibition of Aurora B phosphorylation at Thr232 residue in human HeLa cells after 12 hrs by ELISA, IC50=0.148μM 30502115
A549 Antiproliferative assay 48 hrs Antiproliferative activity against human A549 cells after 48 hrs by MTT assay, GI50=35.8μM 30502115
LoVo Antiproliferative assay 48 hrs Antiproliferative activity against human LoVo cells after 48 hrs by MTT assay, GI50=45.3μM 30502115
HeLa Antiproliferative assay 48 hrs Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay, GI50=46.2μM 30502115
A549 Antiproliferative assay 48 hrs Antiproliferative activity against human A549 cells after 48 hrs by MTT assay, IC50=35.8μM 30728112
LoVo Antiproliferative assay 48 hrs Antiproliferative activity against human LoVo cells after 48 hrs by MTT assay, IC50=45.3μM 30728112
HeLa Antiproliferative assay 48 hrs Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay, IC50=46.2μM 30728112
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 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
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 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
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
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY 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
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 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
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 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
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 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
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
NCI-H358 Antiproliferative assay Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant at 28038940
NCI-H23 Antiproliferative assay Antiproliferative activity against human NCI-H23 cells harboring KRAS G12C mutant at 28038940
Hela Function assay Inhibition of recombinant Aurora A kinase derived from human Hela cells using kemptide as substrate in presence of [c-32P]ATP, Ki=0.002μM 27884697
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells, IC50=0.12μM 23808327
HCT116 Function assay Inhibition of Aurora B kinase assessed as reduction in histone H3 phosphorylation in human HCT116 cells, IC50=0.055μM 21802948
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells, IC50=0.028μM 21802948
insect Function assay Inhibition of human recombinant His-tagged Aurora A kinase expressed in insect cells, IC50=0.0007μM 21194953
BA/F3 Function assay Inhibition of Bcr-Abl T315I mutant autophosphorylation in mouse BA/F3 cells, IC50=5μM 20604564
BA/F3 Antiproliferative assay Antiproliferative activity against mouse BA/F3 cells expressing Bcr-Abl T315I mutant, IC50=0.03μM 20604564
HeLa Function assay Inhibition of phosphotransferase activity of recombinant aurora A expressed in HeLa cells, Ki=0.002μM 20573509
HCT116 Cytotoxicity assay Cytotoxicity against human HCT116 cells by MTS assay, IC50=0.12μM 20550212
COLO205 Antiproliferative assay Antiproliferative activity against human COLO205 cells by [3H]thymidine uptake assay, IC50=0.019μM 19447622
H29 Function assay Inhibition of Aurora B assessed as loss of phospho histone H3 in human H29 cells, IC50=0.74μM 18630890
HCT Function assay Inhibition of Aurora B assessed as loss of phospho histone H3 in human HCT cells, IC50=0.31μM 18630890
HCT Function assay Inhibition of Aurora A assessed as separation of centrosomes in human HCT cells, IC50=0.31μM 18630890
HCT Function assay Inhibition of Aurora A in human HCT cells assessed as loss of autophosphorylation of Aurora A, IC50=0.31μM 18630890
HT29 Antiproliferative assay Antiproliferative activity against human HT29 cells, IC50=0.15μM 18630890
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells, IC50=0.053μM 18630890
MCF7 Antiproliferative assay Antiproliferative activity against human MCF7 cells, IC50=0.048μM 18630890
TE-5 Growth Inhibition Assay IC50=49.7118 μM SANGRER
NCI-H345 Growth Inhibition Assay IC50=48.468 μM SANGRER
TE-6 Growth Inhibition Assay IC50=48.446 μM SANGRER
L-363 Growth Inhibition Assay IC50=46.881 μM SANGRER
HD-MY-Z Growth Inhibition Assay IC50=46.4612 μM SANGRER
LS-513 Growth Inhibition Assay IC50=45.9156 μM SANGRER
COR-L88 Growth Inhibition Assay IC50=45.2778 μM SANGRER
DG-75 Growth Inhibition Assay IC50=45.1577 μM SANGRER
NCI-H1694 Growth Inhibition Assay IC50=44.9472 μM SANGRER
GI-1 Growth Inhibition Assay IC50=42.9192 μM SANGRER
BC-1 Growth Inhibition Assay IC50=42.6731 μM SANGRER
KU812 Growth Inhibition Assay IC50=41.507 μM SANGRER
GDM-1 Growth Inhibition Assay IC50=38.9116 μM SANGRER
JAR Growth Inhibition Assay IC50=38.2449 μM SANGRER
SNU-C2B Growth Inhibition Assay IC50=38.1654 μM SANGRER
NCI-H1155 Growth Inhibition Assay IC50=37.815 μM SANGRER
ES3 Growth Inhibition Assay IC50=36.675 μM SANGRER
HCC2157 Growth Inhibition Assay IC50=35.4619 μM SANGRER
TE-441-T Growth Inhibition Assay IC50=34.6371 μM SANGRER
KNS-81-FD Growth Inhibition Assay IC50=34.5456 μM SANGRER
A253 Growth Inhibition Assay IC50=33.5852 μM SANGRER
A704 Growth Inhibition Assay IC50=33.5538 μM SANGRER
COLO-684 Growth Inhibition Assay IC50=32.6438 μM SANGRER
RXF393 Growth Inhibition Assay IC50=32.497 μM SANGRER
CHP-126 Growth Inhibition Assay IC50=31.1984 μM SANGRER
LB996-RCC Growth Inhibition Assay IC50=31.1702 μM SANGRER
KNS-42 Growth Inhibition Assay IC50=30.8956 μM SANGRER
Raji Growth Inhibition Assay IC50=30.5592 μM SANGRER
SW962 Growth Inhibition Assay IC50=30.2747 μM SANGRER
SNU-C1 Growth Inhibition Assay IC50=28.943 μM SANGRER
U-266 Growth Inhibition Assay IC50=28.6366 μM SANGRER
MZ2-MEL Growth Inhibition Assay IC50=28.6143 μM SANGRER
MHH-PREB-1 Growth Inhibition Assay IC50=28.0734 μM SANGRER
TGBC1TKB Growth Inhibition Assay IC50=27.5585 μM SANGRER
LB2518-MEL Growth Inhibition Assay IC50=27.1773 μM SANGRER
NCI-H748 Growth Inhibition Assay IC50=25.7627 μM SANGRER
no-11 Growth Inhibition Assay IC50=25.747 μM SANGRER
MPP-89 Growth Inhibition Assay IC50=25.5314 μM SANGRER
KP-N-RT-BM-1 Growth Inhibition Assay IC50=25.4752 μM SANGRER
REH Growth Inhibition Assay IC50=25.4671 μM SANGRER
NCI-H889 Growth Inhibition Assay IC50=25.1931 μM SANGRER
LB831-BLC Growth Inhibition Assay IC50=25.1526 μM SANGRER
KLE Growth Inhibition Assay IC50=22.1903 μM SANGRER
BOKU Growth Inhibition Assay IC50=21.4533 μM SANGRER
LP-1 Growth Inhibition Assay IC50=21.3432 μM SANGRER
EVSA-T Growth Inhibition Assay IC50=21.1499 μM SANGRER
CAL-148 Growth Inhibition Assay IC50=20.9934 μM SANGRER
GI-ME-N Growth Inhibition Assay IC50=19.8227 μM SANGRER
IST-MES1 Growth Inhibition Assay IC50=19.6663 μM SANGRER
SK-MM-2 Growth Inhibition Assay IC50=19.555 μM SANGRER
Calu-6 Growth Inhibition Assay IC50=19.239 μM SANGRER
SF539 Growth Inhibition Assay IC50=17.9922 μM SANGRER
HH Growth Inhibition Assay IC50=17.1963 μM SANGRER
ES6 Growth Inhibition Assay IC50=16.2361 μM SANGRER
JiyoyeP-2003 Growth Inhibition Assay IC50=15.6326 μM SANGRER
MZ7-mel Growth Inhibition Assay IC50=14.4433 μM SANGRER
NCI-H1417 Growth Inhibition Assay IC50=14.3052 μM SANGRER
LS-123 Growth Inhibition Assay IC50=14.1588 μM SANGRER
CTB-1 Growth Inhibition Assay IC50=14.0329 μM SANGRER
EW-3 Growth Inhibition Assay IC50=13.7402 μM SANGRER
IST-MEL1 Growth Inhibition Assay IC50=13.5788 μM SANGRER
NEC8 Growth Inhibition Assay IC50=13.1038 μM SANGRER
HCE-T Growth Inhibition Assay IC50=13.0049 μM SANGRER
LC4-1 Growth Inhibition Assay IC50=12.7706 μM SANGRER
KG-1 Growth Inhibition Assay IC50=12.6545 μM SANGRER
NCI-H1882 Growth Inhibition Assay IC50=12.4066 μM SANGRER
A3-KAW Growth Inhibition Assay IC50=12.3236 μM SANGRER
NB1 Growth Inhibition Assay IC50=12.29 μM SANGRER
OPM-2 Growth Inhibition Assay IC50=12.1596 μM SANGRER
DMS-153 Growth Inhibition Assay IC50=12.0426 μM SANGRER
NCI-H1355 Growth Inhibition Assay IC50=11.9426 μM SANGRER
NB69 Growth Inhibition Assay IC50=11.7705 μM SANGRER
TALL-1 Growth Inhibition Assay IC50=11.4058 μM SANGRER
LB373-MEL-D Growth Inhibition Assay IC50=11.3827 μM SANGRER
SJSA-1 Growth Inhibition Assay IC50=11.2891 μM SANGRER
NCCIT Growth Inhibition Assay IC50=11.0582 μM SANGRER
SNB75 Growth Inhibition Assay IC50=10.076 μM SANGRER
KY821 Growth Inhibition Assay IC50=9.77484 μM SANGRER
8-MG-BA Growth Inhibition Assay IC50=9.32844 μM SANGRER
NCI-H1770 Growth Inhibition Assay IC50=8.90265 μM SANGRER
KALS-1 Growth Inhibition Assay IC50=8.83851 μM SANGRER
CP67-MEL Growth Inhibition Assay IC50=8.5326 μM SANGRER
GCIY Growth Inhibition Assay IC50=8.36965 μM SANGRER
NCI-H526 Growth Inhibition Assay IC50=8.25637 μM SANGRER
IA-LM Growth Inhibition Assay IC50=7.859 μM SANGRER
NCI-H1436 Growth Inhibition Assay IC50=7.69932 μM SANGRER
KM-H2 Growth Inhibition Assay IC50=7.18457 μM SANGRER
UACC-257 Growth Inhibition Assay IC50=7.04512 μM SANGRER
NCI-H1581 Growth Inhibition Assay IC50=6.78405 μM SANGRER
LS-1034 Growth Inhibition Assay IC50=6.7566 μM SANGRER
DJM-1 Growth Inhibition Assay IC50=6.34666 μM SANGRER
OS-RC-2 Growth Inhibition Assay IC50=5.98597 μM SANGRER
NCI-H1648 Growth Inhibition Assay IC50=5.81454 μM SANGRER
Daudi Growth Inhibition Assay IC50=5.6912 μM SANGRER
NCI-H2126 Growth Inhibition Assay IC50=5.64574 μM SANGRER
TE-1 Growth Inhibition Assay IC50=5.49004 μM SANGRER
TK10 Growth Inhibition Assay IC50=5.35469 μM SANGRER
MC-CAR Growth Inhibition Assay IC50=5.06757 μM SANGRER
SF268 Growth Inhibition Assay IC50=4.79916 μM SANGRER
COR-L279 Growth Inhibition Assay IC50=4.75891 μM SANGRER
HC-1 Growth Inhibition Assay IC50=4.69494 μM SANGRER
LU-139 Growth Inhibition Assay IC50=4.61835 μM SANGRER
TE-12 Growth Inhibition Assay IC50=4.56394 μM SANGRER
SW872 Growth Inhibition Assay IC50=4.3434 μM SANGRER
NMC-G1 Growth Inhibition Assay IC50=4.22723 μM SANGRER
MMAC-SF Growth Inhibition Assay IC50=4.02467 μM SANGRER
MZ1-PC Growth Inhibition Assay IC50=3.9924 μM SANGRER
MHH-NB-11 Growth Inhibition Assay IC50=3.95312 μM SANGRER
NCI-H747 Growth Inhibition Assay IC50=3.94221 μM SANGRER
ES1 Growth Inhibition Assay IC50=3.92293 μM SANGRER
NCI-H2171 Growth Inhibition Assay IC50=3.92423 μM SANGRER
NOS-1 Growth Inhibition Assay IC50=3.84754 μM SANGRER
HEL Growth Inhibition Assay IC50=3.632 μM SANGRER
RPMI-8402 Growth Inhibition Assay IC50=3.58603 μM SANGRER
PF-382 Growth Inhibition Assay IC50=3.35778 μM SANGRER
LOUCY Growth Inhibition Assay IC50=3.18693 μM SANGRER
TE-9 Growth Inhibition Assay IC50=3.26736 μM SANGRER
RH-1 Growth Inhibition Assay IC50=3.17291 μM SANGRER
NOMO-1 Growth Inhibition Assay IC50=3.02274 μM SANGRER
NCI-H209 Growth Inhibition Assay IC50=2.91253 μM SANGRER
LU-134-A Growth Inhibition Assay IC50=2.8926 μM SANGRER
LB1047-RCC Growth Inhibition Assay IC50=2.88126 μM SANGRER
SK-N-FI Growth Inhibition Assay IC50=2.86868 μM SANGRER
NCI-H2107 Growth Inhibition Assay IC50=2.83711 μM SANGRER
NCI-H82 Growth Inhibition Assay IC50=2.83838 μM SANGRER
TGW Growth Inhibition Assay IC50=2.65832 μM SANGRER
ACN Growth Inhibition Assay IC50=2.50213 μM SANGRER
K5 Growth Inhibition Assay IC50=2.40319 μM SANGRER
OVCAR-4 Growth Inhibition Assay IC50=2.4613 μM SANGRER
IST-SL1 Growth Inhibition Assay IC50=2.29765 μM SANGRER
SH-4 Growth Inhibition Assay IC50=2.32469 μM SANGRER
NB17 Growth Inhibition Assay IC50=2.2927 μM SANGRER
NCI-H720 Growth Inhibition Assay IC50=2.06244 μM SANGRER
RPMI-6666 Growth Inhibition Assay IC50=2.16207 μM SANGRER
ATN-1 Growth Inhibition Assay IC50=2.02858 μM SANGRER
KARPAS-45 Growth Inhibition Assay IC50=2.02654 μM SANGRER
SCLC-21H Growth Inhibition Assay IC50=1.97057 μM SANGRER
GB-1 Growth Inhibition Assay IC50=2.01647 μM SANGRER
A101D Growth Inhibition Assay IC50=1.87395 μM SANGRER
NCI-H1304 Growth Inhibition Assay IC50=1.83073 μM SANGRER
KURAMOCHI Growth Inhibition Assay IC50=1.78911 μM SANGRER
TE-8 Growth Inhibition Assay IC50=1.80368 μM SANGRER
NCI-H1963 Growth Inhibition Assay IC50=1.70583 μM SANGRER
NB5 Growth Inhibition Assay IC50=1.64229 μM SANGRER
MOLT-16 Growth Inhibition Assay IC50=1.35405 μM SANGRER
CMK Growth Inhibition Assay IC50=1.42117 μM SANGRER
GT3TKB Growth Inhibition Assay IC50=1.28057 μM SANGRER
DEL Growth Inhibition Assay IC50=1.25643 μM SANGRER
SK-LMS-1 Growth Inhibition Assay IC50=1.22212 μM SANGRER
EW-1 Growth Inhibition Assay IC50=1.18562 μM SANGRER
SK-NEP-1 Growth Inhibition Assay IC50=1.21111 μM SANGRER
BB65-RCC Growth Inhibition Assay IC50=1.18005 μM SANGRER
HAL-01 Growth Inhibition Assay IC50=1.16709 μM SANGRER
ETK-1 Growth Inhibition Assay IC50=1.13613 μM SANGRER
TE-10 Growth Inhibition Assay IC50=1.12946 μM SANGRER
SBC-1 Growth Inhibition Assay IC50=1.12542 μM SANGRER
HL-60 Growth Inhibition Assay IC50=1.06574 μM SANGRER
NKM-1 Growth Inhibition Assay IC50=1.02775 μM SANGRER
HCC1187 Growth Inhibition Assay IC50=1.00505 μM SANGRER
DU-4475 Growth Inhibition Assay IC50=1.01756 μM SANGRER
SK-N-DZ Growth Inhibition Assay IC50=0.96189 μM SANGRER
SF126 Growth Inhibition Assay IC50=0.94819 μM SANGRER
ES4 Growth Inhibition Assay IC50=0.91128 μM SANGRER
ML-2 Growth Inhibition Assay IC50=0.90259 μM SANGRER
ALL-PO Growth Inhibition Assay IC50=0.88175 μM SANGRER
KGN Growth Inhibition Assay IC50=0.89995 μM SANGRER
HCE-4 Growth Inhibition Assay IC50=0.88063 μM SANGRER
TGBC24TKB Growth Inhibition Assay IC50=0.86385 μM SANGRER
HOP-62 Growth Inhibition Assay IC50=0.86329 μM SANGRER
TE-15 Growth Inhibition Assay IC50=0.85098 μM SANGRER
HCC1599 Growth Inhibition Assay IC50=0.80874 μM SANGRER
MC116 Growth Inhibition Assay IC50=0.85011 μM SANGRER
SK-PN-DW Growth Inhibition Assay IC50=0.7914 μM SANGRER
NB6 Growth Inhibition Assay IC50=0.77254 μM SANGRER
IST-SL2 Growth Inhibition Assay IC50=0.71982 μM SANGRER
CCRF-CEM Growth Inhibition Assay IC50=0.65346 μM SANGRER
ONS-76 Growth Inhibition Assay IC50=0.66458 μM SANGRER
OCI-AML2 Growth Inhibition Assay IC50=0.64403 μM SANGRER
NCI-H187 Growth Inhibition Assay IC50=0.6413 μM SANGRER
HT-144 Growth Inhibition Assay IC50=0.63798 μM SANGRER
CTV-1 Growth Inhibition Assay IC50=0.58773 μM SANGRER
NCI-SNU-16 Growth Inhibition Assay IC50=0.63571 μM SANGRER
LS-411N Growth Inhibition Assay IC50=0.57752 μM SANGRER
KP-N-YS Growth Inhibition Assay IC50=0.54392 μM SANGRER
KE-37 Growth Inhibition Assay IC50=0.52102 μM SANGRER
NCI-H510A Growth Inhibition Assay IC50=0.43823 μM SANGRER
NCI-H524 Growth Inhibition Assay IC50=0.51147 μM SANGRER
K-562 Growth Inhibition Assay IC50=0.43472 μM SANGRER
QIMR-WIL Growth Inhibition Assay IC50=0.42676 μM SANGRER
RL95-2 Growth Inhibition Assay IC50=0.40567 μM SANGRER
BL-70 Growth Inhibition Assay IC50=0.38974 μM SANGRER
LXF-289 Growth Inhibition Assay IC50=0.40406 μM SANGRER
MRK-nu-1 Growth Inhibition Assay IC50=0.3813 μM SANGRER
KARPAS-422 Growth Inhibition Assay IC50=0.37272 μM SANGRER
LAMA-84 Growth Inhibition Assay IC50=0.35178 μM SANGRER
IMR-5 Growth Inhibition Assay IC50=0.3554 μM SANGRER
A388 Growth Inhibition Assay IC50=0.34086 μM SANGRER
DOHH-2 Growth Inhibition Assay IC50=0.33781 μM SANGRER
EoL-1-cell Growth Inhibition Assay IC50=0.33459 μM SANGRER
RKO Growth Inhibition Assay IC50=0.30813 μM SANGRER
CESS Growth Inhibition Assay IC50=0.31328 μM SANGRER
NB13 Growth Inhibition Assay IC50=0.27984 μM SANGRER
EM-2 Growth Inhibition Assay IC50=0.26641 μM SANGRER
MEG-01 Growth Inhibition Assay IC50=0.27849 μM SANGRER
SR Growth Inhibition Assay IC50=0.24564 μM SANGRER
KM12 Growth Inhibition Assay IC50=0.2636 μM SANGRER
EW-16 Growth Inhibition Assay IC50=0.23768 μM SANGRER
KS-1 Growth Inhibition Assay IC50=0.23785 μM SANGRER
MOLT-4 Growth Inhibition Assay IC50=0.23337 μM SANGRER
BB30-HNC Growth Inhibition Assay IC50=0.22591 μM SANGRER
ST486 Growth Inhibition Assay IC50=0.23087 μM SANGRER
PSN1 Growth Inhibition Assay IC50=0.22026 μM SANGRER
LB647-SCLC Growth Inhibition Assay IC50=0.21523 μM SANGRER
VA-ES-BJ Growth Inhibition Assay IC50=0.20086 μM SANGRER
SW982 Growth Inhibition Assay IC50=0.2138 μM SANGRER
K052 Growth Inhibition Assay IC50=0.1948 μM SANGRER
OCUB-M Growth Inhibition Assay IC50=0.16983 μM SANGRER
SK-UT-1 Growth Inhibition Assay IC50=0.15965 μM SANGRER
SIG-M5 Growth Inhibition Assay IC50=0.16707 μM SANGRER
TE-11 Growth Inhibition Assay IC50=0.14982 μM SANGRER
BV-173 Growth Inhibition Assay IC50=0.12641 μM SANGRER
SW954 Growth Inhibition Assay IC50=0.12229 μM SANGRER
A4-Fuk Growth Inhibition Assay IC50=0.11563 μM SANGRER
LC-2-ad Growth Inhibition Assay IC50=0.08789 μM SANGRER
BL-41 Growth Inhibition Assay IC50=0.10445 μM SANGRER
MONO-MAC-6 Growth Inhibition Assay IC50=0.07879 μM SANGRER
MV-4-11 Growth Inhibition Assay IC50=0.07782 μM SANGRER
ES8 Growth Inhibition Assay IC50=0.04613 μM SANGRER
HUTU-80 Growth Inhibition Assay IC50=0.05299 μM SANGRER
NALM-6 Growth Inhibition Assay IC50=0.02552 μM SANGRER
697 Growth Inhibition Assay IC50=0.02471 μM SANGRER
NTERA-S-cl-D1 Growth Inhibition Assay IC50=0.01434 μM SANGRER
MFH-ino Growth Inhibition Assay IC50=0.0099 μM SANGRER
BE-13 Growth Inhibition Assay IC50=0.00338 μM SANGRER
RS4-11 Growth Inhibition Assay IC50=0.00404 μM SANGRER
Sf9 Function assay Inhibition of GST-tagged AURORA A (unknown origin) expressed in baculovirus infected Sf9 cells using MBP as substrate, IC50=0.023μM 30234987
點(diǎn)擊查看更多細(xì)胞系數(shù)據(jù)

生物活性

產(chǎn)品描述 Tozasertib (VX-680)是一種pan-Aurora抑制劑，對(duì)Aurora A作用最強(qiáng)，無(wú)細(xì)胞試驗(yàn)中Kiapp為0.6 nM，而對(duì)Aurora B/Aurora C的作用較弱，對(duì)Aurora A選擇性比其他55種激酶高100倍。唯二的例外是 Fms-related tyrosine kinase-3 (FLT-3) 和 BCR-ABL tyrosine kinase，也可被 Tozasertib 抑制，對(duì)應(yīng)的Ki值均為30 nM和30 nM。Tozasertib 可誘導(dǎo)凋亡和自噬。Phase 2。
靶點(diǎn)
Aurora A [1]
(Cell-free assay)		 Aurora C [1]
(Cell-free assay)		 Aurora B [1]
(Cell-free assay)		 FLT3 [4]
(Cell-free assay)		 Bcr-Abl [4]
(Cell-free assay)
0.6 nM(Ki app) 4.6 nM(Ki app) 18 nM(Ki app) 30 nM(Ki) 30 nM(Ki)
體外研究(In Vitro)
體外研究活性 雖然VX-680具有多激酶特性，VX-680卻誘導(dǎo)相似的細(xì)胞毒性，IC50約為300 nM，在G2/M期，核內(nèi)復(fù)制期，及轉(zhuǎn)染ABL或FLT-3激酶的BaF3細(xì)胞凋亡時(shí)，顯示一個(gè)Aurora B 類(lèi)似的抑制表現(xiàn)型。VX-680抑制CAL-62細(xì)胞增殖，這種作用存在時(shí)間依賴(lài)性。用VX-680處理14天，明顯降低群體的數(shù)量和大小，處理8305C下降達(dá)到70%，處理CAL-62, 8505C,和BHT-101下降達(dá)到90%。用VX-680處理不同ATC細(xì)胞，抑制細(xì)胞增殖，IC50為25到150 ?nM，這種作用存在時(shí)間和劑量依賴(lài)性。在軟瓊脂中，VX-680明顯削弱不同細(xì)胞系形成群落的能力。caspase-3的活性分析顯示VX-680誘導(dǎo)不同細(xì)胞凋亡。VX-680處理CAL-62 細(xì)胞12小時(shí)，形成DNA含量≥4N細(xì)胞累積物。微速攝影分析顯示VX-680處理的CAL-62細(xì)胞離開(kāi)細(xì)胞中期。VX-680可以抑制組蛋白H3的磷酸化作用。[2] VX-680作用于攜帶T315I突變的BCR-Abl的病人樣本，具有明顯抑制活性。[3]
激酶實(shí)驗(yàn) 激酶抑制實(shí)驗(yàn)
丙酮酸激酶/乳酸脫氫酶催化NADH的氧化，伴隨著ATP的消耗，觀察340 nm 處吸光值的降低。反應(yīng)包括100 mM Tris (pH 為 8), 10 mM MgCl2, 2.2 mM ATP, 1 mM磷酸烯醇丙酮酸, 0.6 mg/ml NADH, 75 ml丙酮酸激酶, 105 ml 乳酸脫氫酶,和0.5 mM 基底肽(序列為EAIYAAPFAKKK)。加入足夠的激酶開(kāi)始反應(yīng)，反應(yīng)的激酶濃度達(dá)到30 nM，用微量滴定板分光光度計(jì)在30oC進(jìn)行30分鐘，觀察吸收率的降低。通過(guò)加入3.75 μl 溶于100% DMSO的VX-680 或單獨(dú)DMSO，獲得抑制常數(shù)。按如下公式計(jì)算Ki值，Ki = IC50/(1+[S]/Kd),[S]=[ATP]=2.2 mM, Kd=70 μM。假定作用于野生型和H396P Abl 激酶域的Kd(ATP)為70 μM，計(jì)算以上各值。
細(xì)胞實(shí)驗(yàn) 細(xì)胞系 CAL-62細(xì)胞
濃度 5-500 nM
孵育時(shí)間 4天
方法

對(duì)照組CAL-62細(xì)胞培養(yǎng)在二甲亞砜和DMSO中，實(shí)驗(yàn)組加入500?nM VX-680，處理1到5天。加入不同濃度(5到500?nM) Aurora抑制劑處理不同ATC細(xì)胞4天，用來(lái)測(cè)定VX-680作用于細(xì)胞增殖的劑量依賴(lài)性。細(xì)胞在溫育結(jié)束前加30?mM BrdU標(biāo)記，脈沖2小時(shí)。通過(guò)比色免疫分析使用細(xì)胞增殖ELISA試劑盒分析BrdU的合并率。通過(guò)比較VX-680處理的細(xì)胞和對(duì)照組細(xì)胞得到結(jié)果，
實(shí)驗(yàn)圖片 檢測(cè)方法 檢測(cè)指標(biāo) 實(shí)驗(yàn)圖片 PMID
Western blot DLK / p-MKK7 / MKK7 / p-JNK / JNK p-AURKA / AURKA / Survivin YAP p-AKT / p-GSK3β / Cleaved caspase-3 / Cleaved PARP 23431148
Immunofluorescence α-tubulin / Aurora-A 21600017
Growth inhibition assay Cell viability 21600017
體內(nèi)研究(In Vivo)
體內(nèi)研究活性 VX-680作用于人類(lèi)AML(HL-60)移植瘤模型明顯降低腫瘤尺寸。VX-680按75 mg/kg劑量給藥實(shí)驗(yàn)鼠,每天腹腔注射兩次，持續(xù)13天,與對(duì)照組相比，平均腫瘤體積下降達(dá)98%。腫瘤體積比實(shí)驗(yàn)之前初始體積小很多。按12.5 mg/kg劑量每天給藥兩次，腫瘤生長(zhǎng)也明顯降低，這種作用存在劑量依賴(lài)性。VX-680耐受性很好，只有在使用高劑量時(shí)可以觀察到實(shí)驗(yàn)動(dòng)物體重稍微降低。通過(guò)比較cisplatin,按5.4 mg/kg劑量給藥，每四天腹腔注射一次，一共進(jìn)行三次，抑制腫瘤生長(zhǎng)只達(dá)9%。VX-680作用于胰臟和結(jié)腸移植瘤，也引起腫瘤衰退。VX-680靜脈注射給藥攜帶HCT116腫瘤的實(shí)驗(yàn)鼠，顯示很強(qiáng)的抗癌活性。使用高劑量VX-680(每小時(shí)2 mg/kg)處理，明顯提高效果，比實(shí)驗(yàn)錢(qián)的初始腫瘤平均尺寸下降56%。[1]
動(dòng)物實(shí)驗(yàn) Animal Models 右側(cè)腋窩處皮下注射107 HL-60白血病細(xì)胞的雌性無(wú)胸腺NCr-nu鼠
Dosages 50 mg/kg, 75 mg/kg
Administration 腹腔注射
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00290550 Terminated
Carcinoma Non-Small-Cell Lung
Merck Sharp & Dohme LLC
 June 2006 Phase 2
NCT00111683 Completed
Chronic Myelogenous Leukemia in Blast Crisis|Lymphocytic Leukemia B Cell Acute|Myelodysplastic Syndromes|Myelogenous Leukemia Chronic
Merck Sharp & Dohme LLC
 June 2005 Phase 1

化學(xué)信息&溶解度

分子量 464.59 分子式

C23H28N8OS
CAS號(hào) 639089-54-6 SDF Download Tozasertib (VX-680) SDF
Smiles CC1=CC(=NN1)NC2=CC(=NC(=N2)SC3=CC=C(C=C3)NC(=O)C4CC4)N5CCN(CC5)C
儲(chǔ)存條件(自收到貨起)

體外溶解度
批次：

DMSO : 93 mg/mL ( (200.17 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

 動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量 濃度 體積 分子量

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

mg/kg g μL 只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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