HI-TOPK-032

• CAT Number: I013633
• CAS Number: 487020-03-1
• Molecular Formula: C20H11N5OS
• Molecular Weight: 369.40
• Purity: ≥95%
• Synonyms: N-(12-cyanoindolizino[2,3-b]quinoxalin-2-yl)thiophene-2-carboxamide
• InChI: InChI=1S/C20H11N5OS/c21-11-13-16-10-12(22-20(26)17-6-3-9-27-17)7-8-25(16)19-18(13)23-14-4-1-2-5-15(14)24-19/h1-10H,(H,22,26)
• InChIKey: BCSBXWKRZUPFHW-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)N=C3C(=C4C=C(C=CN4C3=N2)NC(=O)C5=CC=CS5)C#N

HI-TOPK-032 is a potent and specific TOPK inhibitor.
HI-TOPK-032 strongly suppresses TOPK kinase activity but has little effect on extracellular signal-regulated kinase 1 (ERK1), c-jun-NH2-kinase 1, or p38 kinase activities. HI-TOPK-032 occupies the ATP-binding site of TOPK and fits the binding site very well. The compound forms hydrogen bonds with GLY83 and ASP151 and has a hydrophobic interaction with LYS30. However, HI-TOPK-032 at the highest concentration (5 μM) also inhibits MEK1 activity by 40%. HI-TOPK-032 also inhibits anchorage-dependent and -independent colon cancer cell growth by reducing ERK-RSK phosphorylation as well as increasing colon cancer cell apoptosis through regulation of the abundance of p53, cleaved caspase-7, and cleaved PARP[1].
Treatment of mice with 1 or 10 mg/kg of HI-TOPK-032 significantly inhibits HCT-116 tumor growth by more than 60% relative to the vehicle-treated group. Mice are well tolerated with HI-TOPK-032 treatment. The expression of p53 is strongly induced, and phosphorylation of ERK and RSK, a direct downstream protein of ERK, is markedly inhibited in the HI-TOPK-032-treated group[1].

Reference

[1]. Kim DJ, et al. Novel TOPK inhibitor HI-TOPK-032 effectively suppresses colon cancer growth. Cancer Res. 2012 Jun 15;72(12):3060-8.
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