TCS7010(Aurora A Inhibitor I)

Molecular Weight (MW)	588.07
Formula	C31H31ClFN7O2
CAS No.	1158838-45-9
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 118 mg/mL (200.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Other info	Chemical Name: N-(2-Chlorophenyl)-4-[[2-[[4-[2-(4-ethyl-1-piperazinyl)-2-oxoethyl]phenyl]amino]-5-fluoro-4-pyrimidinyl]amino]-benzamide InChi Key: AKSIZPIFQAYJGF-UHFFFAOYSA-N InChi Code: InChI=1S/C31H31ClFN7O2/c1-2-39-15-17-40(18-16-39)28(41)19-21-7-11-24(12-8-21)36-31-34-20-26(33)29(38-31)35-23-13-9-22(10-14-23)30(42)37-27-6-4-3-5-25(27)32/h3-14,20H,2,15-19H2,1H3,(H,37,42)(H2,34,35,36,38) SMILES Code: O=C(NC1=CC=CC=C1Cl)C2=CC=C(NC3=NC(NC4=CC=C(CC(N5CCN(CC)CC5)=O)C=C4)=NC=C3F)C=C2
Synonyms	TC S 7010; TCS 7010; TC-S7010

Molecular Weight (MW)

588.07

Formula

C31H31ClFN7O2

CAS No.

1158838-45-9

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 118 mg/mL (200.6 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Other info

Chemical Name: N-(2-Chlorophenyl)-4-[[2-[[4-[2-(4-ethyl-1-piperazinyl)-2-oxoethyl]phenyl]amino]-5-fluoro-4-pyrimidinyl]amino]-benzamide

InChi Key: AKSIZPIFQAYJGF-UHFFFAOYSA-N

InChi Code: InChI=1S/C31H31ClFN7O2/c1-2-39-15-17-40(18-16-39)28(41)19-21-7-11-24(12-8-21)36-31-34-20-26(33)29(38-31)35-23-13-9-22(10-14-23)30(42)37-27-6-4-3-5-25(27)32/h3-14,20H,2,15-19H2,1H3,(H,37,42)(H2,34,35,36,38)

SMILES Code: O=C(NC1=CC=CC=C1Cl)C2=CC=C(NC3=NC(NC4=CC=C(CC(N5CCN(CC)CC5)=O)C=C4)=NC=C3F)C=C2

Synonyms

TC S 7010; TCS 7010; TC-S7010

In Vitro	In vitro activity: Aurora A Inhibitor I is a 2,4-dianilinopyrimidine that selectively and potently inhibits Aurora A. Aurora A Inhibitor I effectively inhibits the proliferation of HCT116 and HT29 cells, with IC50 of 190 nM and 2.9 μM, respectively. The Aurora A selectivity of Aurora A Inhibitor I against Aurora B depends on a single amino acid (Thr217) of Aurora A. In KCL-22 cells, Aurora A Inhibitor I (1-5 μM) increases G2/M cell fraction, induces histone H3 serine 10 phosphorylation, and suppresses mitotic Aurora A autophosphorylation on Thr288. Aurora A Inhibitor I (0.5-5 μM) also suppresses cell proliferation in KCL-22 cells, as well as BCR-ABL-negative leukemia cell lines KG-1 and HL-60. Aurora A Inhibitor I effectively induces apoptosis in KCL-22 cells at 5 μM. In a recent study, Aurora A Inhibitor I is also found to inhibit cell growth of HCT116, HT29, and HeLa cells, with IC50 of 377.6 nM, 5.6 μM, and 416 nM. Kinase Assay: Both Auroras A and B are assayed in ELISA format using a GST fusion (pGEX-4T) of the N-terminus of Histone H3 (aa 1–18) as substrate. Plates are coated with 2 μg/mL substrate in PBS then blocked with 1 mg/mL I-block in PBS. Kinase reactions are run for 40 min with 5 ng/mL (0.16 nM) Aurora A or 45 ng/mL (1.1 nM) Aurora B at 30 μM ATP (~ Km) in kinase buffer. Final DMSO concentration is 4%. Product is detected by incubation with antiphosphohistone H3 (Ser10) 6G3 mouse monoclonal antibody and sheep-anti-mouse HRP conjugate, followed by washing and addition of TMB substrate. After quenching with 1 M phosphoric acid, plates are read at 450 nM. Cell Assay: Cells (HCT116 and HT29 cells) are seeded in 384-well plates on day 0 in 50 μL of complete medium and incubated overnight in a 5% CO2atmosphere at 37 °C. On day 1, 10 μL of Aurora A Inhibitor I is added. On day 4, plates are allowed to reach room temperature, and 30 μL Cell Titer-Glo reagent is added to each well to measure total ATP levels. Plates are read after shaking 15 min at room temperature.
In Vivo	NA
Animal model	NA
Formulation & Dosage	NA
References	J Med Chem. 2009 May 28;52(10):3300-7; Carcinogenesis. 2012 Feb;33(2):285-93; ACS Chem Biol. 2012 Jan 20;7(1):185-96.

In Vitro

In vitro activity: Aurora A Inhibitor I is a 2,4-dianilinopyrimidine that selectively and potently inhibits Aurora A. Aurora A Inhibitor I effectively inhibits the proliferation of HCT116 and HT29 cells, with IC50 of 190 nM and 2.9 μM, respectively. The Aurora A selectivity of Aurora A Inhibitor I against Aurora B depends on a single amino acid (Thr217) of Aurora A. In KCL-22 cells, Aurora A Inhibitor I (1-5 μM) increases G2/M cell fraction, induces histone H3 serine 10 phosphorylation, and suppresses mitotic Aurora A autophosphorylation on Thr288. Aurora A Inhibitor I (0.5-5 μM) also suppresses cell proliferation in KCL-22 cells, as well as BCR-ABL-negative leukemia cell lines KG-1 and HL-60. Aurora A Inhibitor I effectively induces apoptosis in KCL-22 cells at 5 μM. In a recent study, Aurora A Inhibitor I is also found to inhibit cell growth of HCT116, HT29, and HeLa cells, with IC50 of 377.6 nM, 5.6 μM, and 416 nM.

Kinase Assay: Both Auroras A and B are assayed in ELISA format using a GST fusion (pGEX-4T) of the N-terminus of Histone H3 (aa 1–18) as substrate. Plates are coated with 2 μg/mL substrate in PBS then blocked with 1 mg/mL I-block in PBS. Kinase reactions are run for 40 min with 5 ng/mL (0.16 nM) Aurora A or 45 ng/mL (1.1 nM) Aurora B at 30 μM ATP (~ Km) in kinase buffer. Final DMSO concentration is 4%. Product is detected by incubation with antiphosphohistone H3 (Ser10) 6G3 mouse monoclonal antibody and sheep-anti-mouse HRP conjugate, followed by washing and addition of TMB substrate. After quenching with 1 M phosphoric acid, plates are read at 450 nM.

Cell Assay: Cells (HCT116 and HT29 cells) are seeded in 384-well plates on day 0 in 50 μL of complete medium and incubated overnight in a 5% CO2atmosphere at 37 °C. On day 1, 10 μL of Aurora A Inhibitor I is added. On day 4, plates are allowed to reach room temperature, and 30 μL Cell Titer-Glo reagent is added to each well to measure total ATP levels. Plates are read after shaking 15 min at room temperature.

In Vivo

Animal model

Formulation & Dosage

References

J Med Chem. 2009 May 28;52(10):3300-7; Carcinogenesis. 2012 Feb;33(2):285-93; ACS Chem Biol. 2012 Jan 20;7(1):185-96.

CAS NO:	1158838-45-9
规格:	≥98%

包装	价格(元)
5mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议