HI TOPK 032

Names

[ Name ]:
HI TOPK 032

[Synonym ]:
HI TOPK 032
HI-TOPK-032
2-Thiophenecarboxamide, N-(12-cyanoindolizino[2,3-b]quinoxalin-2-yl)-
N-(12-cyanoindolizino[2,3-b]quinoxalin-2-yl)thiophene-2-carboxamide
N-(12-Cyanoindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxami de
N-(12-Cyanoindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxamide

Biological Activity

[Description]:

HI-TOPK-032 is a potent and specific TOPK inhibitor.

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> TOPK

Research Areas >> Cancer

[In Vitro]

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].

[In Vivo]

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].

[Kinase Assay]

The effect of HI-TOPK-032 on ERK1, JNK1, and p38 activity is assessed by an in vitro kinase assay using ERK1 (active, 500 ng), inactive RSK2 (ERK1 substrate, 1 μg), JNK1 (active, 50 ng), c-Jun (JNK1 substrate, 1 μg) and p38 (active, 200 ng), and ATF2 (p38 substrate, 500 ng) with [γ-32P]ATP. Briefly, the reaction is carried out in the presence of 10 μCi of [γ-32P]ATP with HI-TOPK-032 (0.5, 1, 2, 5 μM) in 40 μL of reaction buffer. After incubation at room temperature for 30 minutes, the reaction is stopped by adding 10 μL protein loading buffer and the mixture is separated by SDS-PAGE[1].

[Cell Assay]

HCT-116 colon cancer cells are treated with different doses of HI-TOPK-032 (1, 2, 5 μM). After incubation for 1, 2, or 3 days, 20 μL of CellTiter96 AQueous One Solution is added and then cells are incubated for 1 hour at 37°C in a 5% CO2 incubator. Absorbance is measured at 492 nm[1].

[Animal admin]

Mice: Mice are divided into 4 groups: (i) untreated vehicle group; (ii) 1 mg HI-TOPK-032/kg of body weight; (iii) 10 mg HI-TOPK-032/kg of body weight; and (iv) no cells and 10 mg HI-TOPK-032/kg of body weight. HCT-116 cells are suspended in serum-free McCoy 5A medium and inoculated s.c. into the right flank of each mouse. HI-TOPK-032 or vehicle is injected 3 times per week for 25 days. Tumor volume is calculated[1].

[References]

[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.

[Related Small Molecules]

OTS-964 | OTS514

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
415.3±45.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₀H₁₁N₅OS

[ Molecular Weight ]:
369.399

[ Flash Point ]:
204.9±28.7 °C

[ Exact Mass ]:
369.068420

[ PSA ]:
111.32000

[ LogP ]:
2.71

[ Vapour Pressure ]:
0.0±1.0 mmHg at 25°C

[ Index of Refraction ]:
1.808

[ Storage condition ]:
2-8℃

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ RIDADR ]:
NONH for all modes of transport

Articles

PBK/TOPK mediates geranylgeranylation signaling for breast cancer cell proliferation.

Cancer Cell Int. 15 , 27, (2015)

PDZ binding-kinase (PBK) (also named T-lymphokine-activated killer cell-originated protein kinase (TOPK)), a serine/threonine kinase, is tightly controlled in normal tissues but elevated in many tumor...

Related Compounds

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