NQDI-1

Research use only, not for human use.

NQDI-1 is a potent and selective inhibitor of apoptosis signal-regulating kinase 1 (ASK1) with Ki of 500 nM.

NQDI-1 is a potent and selective inhibitor of apoptosis signal-regulating kinase 1 (ASK1) with Ki of 500 nM; inhibits in vivo expression levels of ASK1, phosphorylated (p )JNK, p c Jun, p53 and caspase 3 in Hypoxia-ischemia rat model; enhances endochondral bone formation by increasing chondrocyte survival in mice.

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 Ki of 500 nM. Inhibition of ASK1 by NQDI-1 is competitive with respect to the phosphodonor substrate ATP.

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.

NQDI 1

MAPK/ERK Signaling

MEK

ASK1|MAP3K5

Cancer

——

175026-96-7

319.3108

C19H13NO4

>98% (HPLC)

DMSO: 10 mg/mL

O=C(C1=C2C3=C(NC1=O)C=CC=C3C(C4=C2C=CC=C4)=O)OCC

3H-Naphtho[1,2,3-de]quinoline-1-carboxylic acid, 2,7-dihydro-2,7-dioxo-, ethyl ester

(-20℃)

With Ice Pack

≥ 2 years