GSK-461364

• CAS: 929095-18-1
• Catalog Number: ACM929095181-2
• Category: Inhibitors
• Molecular Weight: 543.60
• Molecular Formula: C27H28F3N5O2S
• Description: GSK-461364 is a Polo-like kinase 1 inhibitor, is also a small molecule Polo-like kinase 1 (PLK1) inhibitor with potential antineoplastic activity. Polo-like kinase 1 inhibitor GSK461364 selectively inhibits Plk1, inducing selective G2/M arrest followed by apoptosis in a variety of tumor cells while causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells. Plk1, named after the polo gene of Drosophila melanogaster, is a serine/threonine protein kinase involved in regulating mitotic spindle function in a non-ATP competitive manner.
• Synonyms: GSK461364; GSK 461364; GSK-461364; GSK461364A; GSK 461364A; GSK-461364A
• IUPAC Name: (R)-5-(6-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazol-1-yl)-3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxamide
• Canonical SMILES: O=C(C1=C(O[C@@H](C2=CC=CC=C2C(F)(F)F)C)C=C(N3C=NC4=CC=C(CN5CCN(C)CC5)C=C34)S1)N
• InChI: InChI=1S/C27H28F3N5O2S/c1-17(19-5-3-4-6-20(19)27(28,29)30)37-23-14-24(38-25(23)26(31)36)35-16-32-21-8-7-18(13-22(21)35)15-34-11-9-33(2)10-12-34/h3-8,13-14,16-17H,9-12,15H2,1-2H3,(H2,31,36)/t17-/m1/s1
• InChI Key: ZHJGWYRLJUCMRT-QGZVFWFLSA-N
• Solubility: Soluble in DMSO, not in water
• Appearance: White solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: GSK461364 is a selective, reversible and ATP-competitive Polo-like kinase 1 (PLK1) inhibitor with a Ki value of 2.2 nM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 59.66; H, 5.19; F, 10.48; N, 12.88; O, 5.89; S, 5.90
• Exact Mass: 543.19158
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: GSK461364 treatment also increased the proportion of sub-G1 cells, which includes apoptotic cells (Figure 2A). Treatment at GI80 resulted in slightly more sub-G1 cells than treatment at GI50, and the effect was most pronounced after 72 hours of treatment. This study confirmed that GI50 GSK461364 concentrations significantly induced apoptosis in SK-N-AS and IMR32 cells using the cell death detection ELISA™ (Figure 2C), and apoptotic cell fractions rose further when GSK461364 concentrations were increased to GI80 or 5-fold GI50. These data demonstrate that GSK461364 inhibits proliferation and induces both cell cycle arrest at the G2/M restriction point and apoptosis in neuroblastoma cells, regardless of MYCN status.; Reference: Oncotarget. 2017 Jan 24;8(4):6730-6741. https://pubmed.ncbi.nlm.nih.gov/28036269/
• In Vivo Activity: GSK461364 treatment also significantly reduced IMR32 xenograft tumor growth compared to the control group (Figure 4B, Supplementary Figure 2B). Immunohistological examination of xenograft tumors showed that GSK461364 reduced the number of proliferating cells and increased the number of apoptotic cells in tumors (Figure 4C). These data clearly demonstrate that GSK461364 treatment in vivo suppresses growth of xenografts derived from neuroblastoma cells with high-risk characteristics regardless of MYCN status.; Reference: Oncotarget. 2017 Jan 24;8(4):6730-6741. https://pubmed.ncbi.nlm.nih.gov/28036269/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).