IDH1 and cancer: Here, we describe studies on the selectivity of cancer-associated IDH1/2 variants with respect to 2OG derivatives, the results of which support the possibility of active site binding–mediated inhibition of IDH1/2 variants, highlight the possibility of non-2OG substrates/inhibitors of IDH1/2 variants, and suggest IDH1/2 variants have potential as biocatalysts.