UNC8732

UNC8732 binds to the recombinant NSD2-PWWP1 domain with a K_D value of 76 nM^[1].
UNC8732 potently induces NSD2 degradation in cultured cells, with a DC₅₀ of 0.06 µM and a D_max of 97%^[1].
UNC8732 (10 µM; 4-6 h) is metabolized into an active aldehyde derivative in the presence of fetal bovine serum (FBS), and this metabolic process is essential for its activity^[1].
Degradation of NSD2 induced by UNC8732 (2.5-5 µM; 24 h) in U2OS cells requires the amine oxidase activity of fetal bovine serum (FBS), as this degradation is completely abolished in FBS-free medium or in the presence of the amine oxidase inhibitor AG^[1].
UNC8732 (5 µM; 150 min) recruits the FBXO22 E3 ligase subunit to NSD2 in Flp-In 293 cells, and proximity biotinylation assays show significant enrichment of FBXO22^[1].
UNC8732 (0.05-40 µM; 3 h) promotes the formation of the ternary complex between NSD2 and FBXO22 in U2OS cells in a dose-dependent manner, which is detectable via increased NanoBRET signal^[1].
UNC8732 (1 µM; 4 h)-mediated degradation of NSD2 in U2OS cells depends on the SCF^FBXO22 E3 ligase complex, as knockdown of CUL1, SKP1 or FBXO22 blocks this degradation process^[1].
UNC8732 (0.5-10 µM; 11-18 days) degrades NSD2, reverses abnormal histone methylation patterns, reduces cell viability and induces apoptosis. It exerts stronger efficacy in RCH-ACV acute lymphoblastic leukemia cells carrying the NSD2^p.E1099K mutation than in wild-type cells, while restoring glucocorticoid sensitivity in the mutant cells^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.