A folate analogue LY3458997,10 (here denoted as compound 5, Figure 2A) inhibited both MTHFD2 (IC50: 663 nM) and MTHFD1 (IC50: 96 nM) and suppressed tumorgrowth in a mice xenograft model of colorectal cancer through intraperitonealinjection.7 Similarly, a natural productnamed carolacton was identified, that binds to both MTHFD1 and MTHFD2with Ki values in the nanomolar range.11 These potent compounds concurrently inhibitMTHFD1/2; however, the inhibition of MTHFD1 could pose a potentialsafety risk and is therefore undesirable due to its high expressionin normal tissues. The gene discussed is MTHFD1; the disease is colorectal cancer.