GSK-1070916

SKU: orb1688748

Description

GSK-1070916

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Signal Transduction

Key Properties

• CAS Number: 942918-07-2
• MW: 507.63
• Purity: 99.73%
• Formula: C₃₀H₃₃N₇O
• SMILES: CCn1cc(c(n1)-c1ccc(NC(=O)N(C)C)cc1)-c1ccnc2[nH]c(cc12)-c1cccc(CN(C)C)c1
• Target: AMPK,Aurora Kinase,FLT,Apoptosis,Tie-2
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (6.5 mM);Ethanol:8 mg/mL (15.76 mM);DMSO:8.53 mg/mL (16.8 mM)

Bioactivity

• Target IC50:
  Aurora C-INCENP:6.5 nM|Aurora B:0.38 nM (Ki)|Aurora B-INCENP:3.5 nM|Aurora C:1.5 nM (Ki)
• In Vivo:
  GSK1070916 (25, 50, or 100 mg/kg) shows dose-dependent Inhibition of phosphorylation of an Aurora B–specific substratee in mice and consistent with its broad cellular activity, has antitumor effects in 10 human tumor xenograft models including breast, colon, lung, and two leukemia models.
• In Vitro:
  GSK1070916 selectively inhibits Aurora B and Aurora C with Ki of 0.38 nM and 1.5 nM over Aurora A with Ki of 490 nM. Inhibition of Aurora B and Aurora C is time-dependent, with an enzyme inhibitor dissociation half-life of >480 min and 270 min respectively In addition, GSK1070916 is also a competitive inhibitor with respect to ATP. Human tumor cells treated with GSK1070916 shows dose-dependent Inhibition of phosphorylation on serine 10 of Histone H3, a substratee specific for Aurora B. Moreover, GSK1070916 inhibit the proliferation of tumor cells with EC50 Values of < 0 nM in over 100 cell lines spanning a broad range of tumor types, with a median EC50 of 8 nM. Although GSK1070916 has potent activity against proliferating cells, a dramatic shift in potency is observed in Primary, nondividing, normal human vein endothelial cells. furthermore , GSK1070916-treated cells do not arrest in mitosis but instead fails to divide and become polyploid, ultimately leading to apoptosis. In a Other study, it is also reported high chromosome number associated with resistance to the Inhibition of Aurora B and C suggests cells with a mechanism to bypas the high ploidy checkpoint are resistant to GSK1070916.
• Cell Research:
  Cells are plated in 96-well plates in the recommended growth media and incubated at 37℃n 5% CO2 overnight the following day the cells are treated with serial dilutions of GSK1070916. At this time, one set of cells is treated with CellTiter-Glo for a time equal to 0 (T = 0) measurement. Following a 6- to 7-d incubation with compound, cell proliferation is measured usin the CellTiter-Glo reagent according to the manufacture's recommended protocol. As Inhibition of Aurora B induces endomitosis the degree of which differs depending o the cell type, an extended compound treatment time is required to accurately reflec the effects on cell viability across a large panel of cell lines. For analysis of cell viability, Values from wells with no cells are subtracted for background correction an the data plotted as a percent o the DMSO-treated control Samples using Microsoft Excel XLfit4 software the EC50 Values represen the concentration of GSK1070916 where 50% maximal effect is observed(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

FLT1, GSK1070916, GSK-1070916, GSK-1070916A, GSK 1070916, Inhibitor, inhibit, Aurora B-INCENP, Aurora C-INCENP, Aurora Kinase, AuroraKinase, Apoptosis, Tie2, Tie-2, SIK

Compound Identifiers

PubChem CID

46885626