N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxaMide Struktur

N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxaMide

Bezeichnung:N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxaMide

CAS-Nr487020-03-1

Englisch Name:N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxaMide

CBNumberCB42695998

SummenformelC20H11N5OS

Molgewicht369.4

MOL-Datei487020-03-1.mol

N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxaMide physikalisch-chemischer Eigenschaften

Siedepunkt	415.3±45.0 °C(Predicted)
Dichte	1.50±0.1 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	DMSO: soluble3mg/mL, clear (warmed)
pka	9.32±0.46(Predicted)
Aggregatzustand	powder
Farbe	orange-brown

Sicherheit

Kennzeichnung gefährlicher	Xn
R-Sätze:	22
WGK Germany	3
HS Code	2922500090

Gefahreninformationscode (GHS)

N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxaMide Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
HI TOPK 032 is an inhibitor of lymphokine-activated killer T cell-originated protein kinase (TOPK), blocking phosphorylation of the substrate histone H2AX with an IC₅₀ value of ~2 μM and providing complete inhibition at 5 μM. It also inhibits checkpoint kinase 1 (Chk1; IC₅₀ = 9.6 μM). In addition, HI TOPK 032 inhibits MEK1, achieving 40% inhibition at 5 μM, but it does not alter the activities of ERK1, JNK1, or p38 MAPK at 2 μM. HI TOPK 032 decreases the growth of colon cancer and glioma initiating cells in vitro and suppresses tumor growth in vivo.
Verwenden
N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxamide is a novel TOPK inhibitor that was shown to effectively suppress colon cancer growth.
Verwenden
HI-TOPK-032 has been used as a PDZ binding-kinase (PBK) inhibitor.
Biologische Aktivität
HI-TOPK-032 is a potent and specific inhibitor of TOPK. HI-TOPK-032 also reduces ERK-RSK phosphorylation, modulates the abundance of p53, cleaved caspase-7, and cleaved PARP, and induces apoptosis in cancer cells.
Biochem/physiol Actions
HI-TOPK-032 is a specific TOPK (T-LAK cell–originated protein kinase) inhibitor both in vitro and in vivo. HI-TOPK-032 suppressed tumor growth in a colon cancer xenograft model.
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.
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.

N-(12-Cyanindolizino[2,3-b]quinoxalin-2-yl)-2-thiophenecarboxaMide Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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