SHIN2 is a folate-competitive, cell-permeable inhibitor of human SHMT1/2 with improved pharmacokinetic properties over SHIN1.
SHIN2 increases survival in NOTCH1-driven mouse primary T-ALL in vivo.
Low dose methotrexate sensitizes Molt4 human T-ALL cells to SHIN2, and cells rendered methotrexate resistant in vitro show enhanced sensitivity to SHIN2.
SHIN2 and methotrexate synergize in mouse primary T-ALL and in a human patient-derived xenograft in vivo, increasing survival.
