MKK7-COV-9 is a selective and potent covalent inhibitor of MKK7 with inhibitory effects on MKK7-induced protein-protein interactions.MKK7-COV-9 interrupts the activation of primary B-cells in response to LPS.MKK7-COV-9 shows low cytotoxicity at high concentrations.

3T3 cells:4.06 μM (EC50)

Due to poor permeability, the piperidine analogs MKK7-COV-10 and MKK7-COV-11, as well as the carboxylic acid MKK7-COV-8, prove to be inactive in ICW in 3T3 cells. In contrast, the amide counterpart, MKK7-COV-9, retains activity (EC50=4.06 μM) and provides a new vector for further derivatization[1].
MKK7-COV-9 (10 μM; 48 hours) shows a limited cytotoxic effect only at the highest tested concentration. Only one cell line, HCT116, displayed a half-maximal lethal dose (LD50) < 10 μM for these two compounds[1].With a 2-hour pre-incubation at 10 μM, MKK7-COV-9 is able to inhibit 60% of the CD86+ response to LPS stimulation in primary mouse B cells, except the negative control MKK7-NEG-1[1].JNK is known to mediate the activation of B cells in response to lipopolysaccharide through the TLR4 signaling pathway.MKK7-COV-9 (0-10 μM; 2 hr pre-incubation) is able to mediate the activation of B cells in response to LPS through the TLR4 signaling pathway. It shows a dose-response curve for the inhibition of LPS-induced activation and exhibits an EC50 value of 4.98 μM (EC50=4.98 μM for MKK7-COV-12; EC50>10 μM for MKK7-COV-7; EC50=2.23 μM for JNK-IN-8)[1].