MKK7-COV-9

MKK7-COV-9 is a potent and selective covalent inhibitor of MKK7 and targets a specific protein-protein interaction of MKK7. MKK7-COV-9 blocks primary B cell activation in response to LPS with an EC₅₀ of 4.98 μM^[1].
In Vitro: Due to poor permeability, the?piperidine?analogs MKK7-COV-10 and MKK7-COV-11 proves to be inactive in ICW in 3T3 cells, as well as the carboxylic acid MKK7-COV-8. In contrast, as an?amide?counterpart , MKK7-COV-9, retains activity (EC₅₀=4.06?μM) and furthermore now provides a new vector for further?derivatization^[1].
MKK7-COV-9 (10?μM; 48 hours) shows limited cytotoxic effect only at the highest tested concentration. Only one cell line, HCT116, displayed?half-maximal lethal dose (LD₅₀)<10?μM for these two compounds^[1].
MKK7-COV-9?(10?μM; 2?hr pre-incubation) is able to inhibit 60% of the CD86⁺ response in response to LPS stimulation,?in primary mouse B cells?, except the negative control MKK7-NEG-1^[1].
JNK is known to mediate activation of B cells in response to?lipopolysaccharide (LPS; HY-D1056) through the?TLR4?signaling pathway.
MKK7-COV-9 (0-10 μM; 2?hr pre-incubation) is able to mediate activation of B cells in response to?LPS through the?TLR4?signaling pathway, it shows a dose-response curves for 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].