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For example, compared to a simpler design ( 1a R -IN-8), kinome-wide selectivity (see 1a R -IN-8 vs 6 S,S -IN-8) or JNK isoform selectivity (see 1a R -IN-8 vs 1b R -IN-8), and even inhibitor efficacy on c-Jun substrate phosphorylation in cells (see Table 1), could be improved by changing the warhead scaffold at this accessible position