JQAD1

JQAD1 is a proteolysis-targeting chimera (PROTAC) composed of the p300 and CREB-binding protein (CBP) inhibitor A-485 (Cay-24119) conjugated to a cereblon (CRBN) ligand. It selectively induces the degradation of p300 over CBP in Kelly MYCN-amplified neuroblastoma cells when used at a concentration of 10 µM for 24 hours. JQAD1 (0.5 µM) decreases histone 3 lysine 27 (H3K27) acetylation and induces apoptosis in Kelly cells. In vivo, JQAD1 (40 mg/kg) decreases tumor volume, increases survival, and reduces tumoral p300 but not CBP levels in a Kelly neuroblastoma mouse xenograft model.Formal Name: 12-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)-((R)-3'-(2-((4-fluorobenzyl)((S)-1,1,1-trifluoropropan-2-yl)amino)-2-oxoethyl)-2',4'-dioxo-2,3-dihydrospiro[indene-1,5'-oxazolidin]-5-yl)dodecanamide. CAS Number: 2417097-18-6. Synonyms: (R,S)-JQAD1. Molecular Formula: C48H52F4N6O9. Formula Weight: 933.0. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble. SMILES: O=C(N1C2C(NC(CC2)=O)=O)C3=CC=C(C=C3C1=O)NCCCCCCCCCCCC(NC4=CC=C5C(CC[C@@]56OC(N(C6=O)CC(N(CC7=CC=C(F)C=C7)[C@H](C(F)(F)F)C)=O)=O)=C4)=O. InChi Code: InChI=1S/C48H52F4N6O9/c1-29(48(50,51)52)56(27-30-12-14-32(49)15-13-30)41(61)28-57-45(65)47(67-46(57)66)23-22-31-25-34(17-19-37(31)47)54-39(59)11-9-7-5-3-2-4-6-8-10-24-53-33-16-18-35-36(26-33)44(64)58(43(35)63)38-20-21-40(60)55-42(38)62/h12-19,25-26,29,38,53H,2-11,20-24,27-28H2,1H3,(H,54,59)(H,55,60,62)/t29-,38?,47+/m0/s1. InChi Key: TWCIGBYYSZQAAA-GWWVHQGYSA-N.