UNC10088 

UNC10088 is a molecular glue targeting NSD2. UNC10088 mediates the formation of a stable ternary complex between SCFFBXO22 and the NSD2 PWWP1 domain. UNC10088 promotes ubiquitination of the SCFFBXO22-dependent NSD2 PWWP1 domain through reversible covalent bonding with the C326 region of FBXO22. UNC10088 could be used in cancer research^[1].

UNC10088 (0.5 μM, 15 min) drives the SCF^FBXO22-dependent polyubiquitination of the NSD2 PWWP1 domain by binding to C326 of FBXO22 to mediate a stable ternary complex, a process reliant on key interacting residues (e.g., FBXO22's E362, K229, E169, and NSD2's F266, E272, K253) wherein mutations disrupt complex stability or degrader positioning and inhibit ubiquitination^[1].
UNC10088's (5 μM, 1 h) binding to the FBXO22 FIST domain is exclusively dependent on Cys326, as complex formation is abolished by the C326A mutation and restored by its singular reintroduction into a cysteine-null background^[1].
UNC10088 (1 h) exhibits a 2.5-fold reduction in IC₅₀ (from 248 nM to 101 nM) upon the addition of FBXO22, indicating positive cooperative binding with an α-factor of 3.3^[1].
UNC10088 significantly increases the melting temperature (Tm) of the FIST domain in wild-type FBXO22; the addition of UNC10088 had almost no effect on the Tm of the C326A mutant^[1].

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

712.74

C₃₅H₃₇N₄NaO₉S

OC(CCCCC(N1CCC2=CC(NC(C3=CC=C(C=C3)CN(C4CC4)C(C5=CC6=C(NC(CO6)=O)C=C5)=O)=O)=CC=C2C1)=O)S(=O)(O[Na])=O

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• [1]. Robertson KC, et al. Structural basis of NSD2 degradation via targeted recruitment of SCF-FBXO22. bioRxiv [Preprint]. 2025 Aug 30:2025.08.29.673087.