(-)-JQ1

• CAT Number: I001076
• CAS Number: 1268524-71-5
• Molecular Formula: C₂₃H₂₅ClN₄O₂S
• Molecular Weight: 456.99
• Purity: ≥95%
• Target: Bromodomain
• Solubility: DMSO >150 mg/mL; Water <1 mg/mL; Ethanol 125 mg/mL
• Storage: 2-8°C
• IUPAC Name: tert-butyl 2-[(9R)-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]acetate
• InChI: InChI=1S/C23H25ClN4O2S/c1-12-13(2)31-22-19(12)20(15-7-9-16(24)10-8-15)25-17(11-18(29)30-23(4,5)6)21-27-26-14(3)28(21)22/h7-10,17H,11H2,1-6H3/t17-/m1/s1
• InChIKey: DNVXATUJJDPFDM-QGZVFWFLSA-N
• SMILES: CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)OC(C)(C)C)C4=CC=C(C=C4)Cl)C

The (R)-(-)-JQ1 enantiomer（Cat No.:I001076）, also known as (+)-JQ1, lacks significant interaction with bromodomains, while the stereoisomer (-)-JQ1 is an inhibitor for the bromodomain and extra-terminal (BET) family of proteins. BET inhibitors, including (-)-JQ1, are known for their ability to disrupt the binding of bromodomains to acetylated histones, thereby modulating gene expression and offering potential therapeutic applications in cancer and other diseases where BET proteins play a critical role. The lack of significant interaction of (+)-JQ1 with bromodomains distinguishes it from its active enantiomer.

Reference

[1]. Filippakopoulos, Panagis et al. Selective inhibition of BET bromodomains From Nature (London, United Kingdom) (2010), 468(7327), 1067-1073.
Abstract
Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic /’writers/’ and /’erasers/’. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. …