product name Aurora A Inhibitor I
Description: Aurora A Inhibitor I is a novel, potent, and selective inhibitor of Aurora A with IC50 of 3.4 nM in a cell-free assay. It is 1000-fold more selective for Aurora A than Aurora B. The inhibitory potencies of Aurora A Inhibitor I was strongly affected by the single amino acid substitutions. For either Aurora kinase, the presence of threonine allowed potent inhibition, while for glutamic acid variants, there was a approximately 100-fold shift in IC50, which supported the “gating” role for this residue.
References: J Med Chem. 2009 May 28;52(10):3300-7; Carcinogenesis. 2012 Feb;33(2):285-93.
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
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19393683
| 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% CO2 atmosphere 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. |
Related Posts
product name Aurora A Inhibitor I
Description: Aurora A Inhibitor I is a novel, potent, and selective inhibitor of Aurora A with IC50 of 3.4 nM in a cell-free assay. It is 1000-fold more selective for Aurora A than Aurora B. The inhibitory potencies of Aurora A Inhibitor I was strongly affected by the single amino acid substitutions. For either Aurora kinase, the presence of threonine allowed potent inhibition, while for glutamic acid variants, there was a approximately 100-fold shift in IC50, which supported the “gating” role for this residue.
References: J Med Chem. 2009 May 28;52(10):3300-7; Carcinogenesis. 2012 Feb;33(2):285-93.
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
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19393683
| 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% CO2 atmosphere 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. |