Wildtype MEFs were seeded in 10 cm tissue culture dishes, at a density of two million cells per dish. Cells were treated with 0.1% DMSO, 300 nM XL01126, or 300 nM cis-XL01126 for 4 hours prior to harvest in 400 µl complete lysis buffer, supplemented with 1 μg/ml microcystin-LR, 1 mM sodium orthovanadate, complete EDTA-free protease inhibitor cocktail (Roche) and 1% (v/v) Triton X-100. Cell lysates were incubated on ice for 10 minutes, then underwent three rounds of high energy sonication for 15 cycles (30 seconds on, 30 seconds off) using the Diagenode Bioruptor. Cell lysates were centrifuged at 15,000 g at 4°C for 15 minutes. Cell pellet was discarded, and supernatant was collected for protein quantification using a BCA protein assay kit (Pierce #23225). 100 µg cell lysate was employed for total proteomic analysis. Proteins in cell lysate were reduced with 0.1 M Tris(2-carboxyethyl)phosphine (TCEP) diluted in 300 mM triethylammonium bicarbonate (TEABC) to a final concentration of 10 mM. Samples were incubated on a Thermomixer for 30 minutes at 60°C at 800 rpm then cooled down to room temperature and underwent alkylation with 0.04 M iodoacetamide (IAA) freshly dissolved in water. Samples were then incubated in the dark on a Thermomixer at room temperature for 30 minutes at 800 rpm. Alkylation was quenched with the addition of 0.1 M TCEP dissolved in 300 mM TEABC at a final concentration of 5 mM. Samples were incubated on a Thermomixer at room temperature for 20 minutes at 800 rpm. Sodium dodecyl sulfate (SDS) was added at a final concentration of 5% (w/v) from a 20% (w/v) stock. 12% (v/v) phosphoric acid was then added to a final concentration of 1.2% (v/v). Samples were diluted in 6 times the sample volume of Strap wash buffer containing 90% (v/v) methanol diluted in 100 mM (v/v) TEAB pH 7.1.