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SGC-GAK-1 (<b>1</b>) is a potent, selective, cell-active chemical probe for cyclin G-associated kinase (GAK). However, <b>1</b> was rapidly metabolized in mouse liver microsomes by cytochrome P450-mediated oxidation, displaying rapid clearance in liver microsomes and in mice, which limited its utility in in vivo studies. Chemical modifications of <b>1</b> that improved metabolic stability, generally resulted in decreased GAK potency. The best analog in terms of GAK activity in cells was 6-bromo-<i>N</i>-(1<i>H</i>-indazol-6-yl)quinolin-4-amine (<b>35</b>) (IC₅₀ = 1.4 &#956;M), showing improved stability in liver microsomes while still maintaining a narrow spectrum activity across the kinome. As an alternative to scaffold modifications we also explored the use of the broad-spectrum cytochrome P450 inhibitor 1-aminobenzotriazole (ABT) to decrease intrinsic clearance of aminoquinoline GAK inhibitors. Taken together, these approaches point towards the development of an in vivo chemical probe for the dark kinase GAK.