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NQDI-1

CAS No. : 175026-96⁻⁷

MCE 国际站：NQDI-1

产品活性：NQDI-1 抑制凋亡信号调节激酶 1 (ASK1)，K_i 为 500 nM，IC₅₀ 为 3 μM。

研究领域：MAPK/ERK Pathway | Apoptosis

作用靶点：MAP3K | Apoptosis

In Vitro: The selectivity of NQDI-1 is evaluated in vitro on four serine/threonine protein kinases (protein kinase CK2 (CK2), c-Jun N-terminal kinase 3 (JNK3), Rho-associated protein kinase 1 (Rock1), ａnd Aurora A) ａnd three tyrosine protein kinases (FGFR1, hHGFR, ａnd endothelial TEK tyrosine kinase (Tie2)). The results show that NQDI-1 is a selective inhibitor of ASK1. The activity of FGFR1 protein kinase is inhibited by NQDI-1 (residual activity of 44%). NQDI-1 inhibits ASK1 with a K_i of 500 nM. Inhibition of ASK1 by NQDI-1 is competitive with respect to the phosphodonor substrate ATP.

In Vivo: 250 nmol NQDI-1 in DMSO is intracerebroventricularly injected following brain insult. Western blotting is performed to determine the expression of ASK1 in the sham, Hypoxia-ischemia (HI), DMSO ａnd NQDI-1 groups ａnd indicate that NQDI-1 markedly inhibits the expression of ASK1 in the brain cortex, compared with the HI ａnd DMSO group. Furthermore, immunofluorescence staining also indicates that the expression of ASK1 is inhibited by NQDI-1 in the brain cortex. The expression of downstream targets of ASK1 is also determined in the present study. The expression levels of p-JNK, p-c-Jun, p53 ａnd caspase 3 are significantly decreased by NQDI-1, compared with the HI ａnd DMSO groups. Low expression of p-JNK in the brain cortex is also observed by immunofluorescence in the NQDI-1-treated group.

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