UNC8153 (trifluoroacetate salt)

UNC8153 is a degrader of the histone-lysine N-methyltransferase NSD2. It induces its degradation of NSD2 with a 50% degradation constant (DC50) value of 350 nM and is selective for NSD2 over NSD1 and NSD3 at 20 µM. UNC8153 (10 µM) induces NSD2 degradation and reduces histone H3 lysine 36 dimethylation (H3K36me2) in MM.1S multiple myeloma cells, an effect that can be inhibited by the inhibitor of the ubiquitin-activating enzyme MLN4924 (Cay-15217). It reduces the proliferation of MM.1S cells expressing NSD2 containing an activating glutamate-to-lysine mutation at position 1099 (NSD2E1099K), but not MDA-MB-231, U2OS, or HEK293 cells expressing wild-type NSD2, when used at a concentration of 20 µM. UNC8153 (20 µM) decreases attachment of MM.1S cells in a migration assay.Formal Name: N-[[4-[[[4-[[(6-aminohexyl)amino]carbonyl]phenyl]amino]carbonyl]phenyl]methyl]-N-cyclopropyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-7-carboxamide, trifluoroacetate salt. CAS Number: 2929304-61-8. Molecular Formula: C33H37N5O5 . CF3COOH. Formula Weight: 697.7. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, Ethanol: 30 mg/ml, PBS (pH 7.2): 5 mg/ml. lambdamax: 282 nm. SMILES: O=C1COC2=C(C=CC(C(N(C3CC3)CC4=CC=C(C(NC5=CC=C(C(NCCCCCCN)=O)C=C5)=O)C=C4)=O)=C2)N1.OC(C(F)(F)F)=O. InChi Code: InChI=1S/C33H37N5O5.C2HF3O2/c34-17-3-1-2-4-18-35-31(40)23-9-12-26(13-10-23)36-32(41)24-7-5-22(6-8-24)20-38(27-14-15-27)33(42)25-11-16-28-29(19-25)43-21-30(39)37-28,3-2(4,5)1(6)7/h5-13,16,19,27H,1-4,14-15,17-18,20-21,34H2,(H,35,40)(H,36,41)(H,37,39),(H,6,7). InChi Key: PRNFABQCXAELBV-UHFFFAOYSA-N.