(+)SHIN2 is a serine droxymetltransferase (SHMT) inhibitor, whose target can be traced with 13C-serine. (+)SHIN2 increases survival in NOTCH1-driven mouse primary acute lymphoblastic leukemia (T-ALL) in vivo with a synergistic effect with Decreased tmus weight and cellularity, which normalized after treatment discontinuation.
Showed generally well tolerated activity with modest hematological toxicity.
[1]. GarcÍa-CaÑaveras JC, et al. SHMT inhibition is effective and synergizes with methotrexate in T-cell acute lymphoblastic leukemia. Leukemia. 2021 Feb;35(2):377-388.