AT6

• CAT Number: I020067
• CAS Number: 2098836-50-9
• Molecular Formula: C₄₈H₅₈ClN₉O₇S₃
• Molecular Weight: 1004.68
• Purity: ≥95%
• Target: PROTACs
• IUPAC Name: (2S,4R)-1-[(2R)-2-acetamido-3-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethylsulfanyl]-3-methylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
• InChI: InChI=1S/C48H58ClN9O7S3/c1-27-29(3)68-47-40(27)41(33-12-14-35(49)15-13-33)54-37(44-56-55-30(4)58(44)47)23-39(61)50-16-17-64-18-19-65-20-21-67-48(6,7)43(53-31(5)59)46(63)57-25-36(60)22-38(57)45(62)51-24-32-8-10-34(11-9-32)42-28(2)52-26-66-42/h8-15,26,36-38,43,60H,16-25H2,1-7H3,(H,50,61)(H,51,62)(H,53,59)/t36-,37+,38+,43-/m1/s1
• InChIKey: ZCEIHPCVOJGWHG-TZPPCSJFSA-N
• SMILES: CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)NCCOCCOCCSC(C)(C)[C@@H](C(=O)N4C[C@@H](C[C@H]4C(=O)NCC5=CC=C(C=C5)C6=C(N=CS6)C)O)NC(=O)C)C7=CC=C(C=C7)Cl)C

AT6(CAT: I020067) is a PROTAC (proteolysis-targeting chimera) and an analogue of AT1, specifically designed as a highly selective degrader of bromodomain-containing protein 4 (Brd4). It operates by recruiting Brd4 to an E3 ubiquitin ligase, facilitating ubiquitination and subsequent proteasomal degradation. AT6 targets the bromodomain BD2 of Brd4 with pronounced cooperative binding in the ternary complex, as demonstrated through isothermal titration calorimetry, mutagenesis, and proximity assays. Its structure optimizes specific intermolecular interactions, contributing to its high selectivity and efficacy in cellular systems. AT6 is a valuable tool for exploring Brd4 biology, chromatin regulation, and the development of targeted therapies for Brd4-related cancers and diseases.