CPI-203

• CAT Number: I001715
• CAS Number: 1446144-04-2
• Molecular Formula: C₁₉H₁₈ClN₅OS
• Molecular Weight: 399.90
• Purity: ≥95%
• Synonyms: (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamide
• Target: Bromodomain
• Solubility: in DMSO > 10 mM
• Storage: 2-8°C
• IC50: 37 nM
• IUPAC Name: 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]acetamide
• InChI: InChI=1S/C19H18ClN5OS/c1-9-10(2)27-19-16(9)17(12-4-6-13(20)7-5-12)22-14(8-15(21)26)18-24-23-11(3)25(18)19/h4-7,14H,8H2,1-3H3,(H2,21,26)/t14-/m0/s1
• InChIKey: QECMENZMDBOLDR-AWEZNQCLSA-N
• SMILES: CC1=C(SC2=C1C(=N[C@H](C3=NN=C(N32)C)CC(=O)N)C4=CC=C(C=C4)Cl)C

I-BET726（Cat No.:I001715）is a potent and selective inhibitor of bromodomain and extra-terminal (BET) proteins, which are critical regulators of gene expression involved in various cellular processes, including inflammation and cancer. By targeting BET proteins, I-BET726 disrupts their interaction with acetylated histones, leading to the suppression of oncogenic transcription programs. This compound has demonstrated efficacy in preclinical studies, showing potential for treating hematological malignancies and solid tumors. I-BET726’s unique mechanism of action makes it a promising candidate for developing targeted therapies aimed at cancers driven by aberrant BET protein activity.

Reference

[1]. Devaiah BN, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6927-32.
Abstract
The bromodomain protein, BRD4, has been identified recently as a therapeutic target in acute myeloid leukemia, multiple myeloma, Burkitt/’s lymphoma, NUT midline carcinoma, colon cancer, and inflammatory disease; its loss is a prognostic signature for metastatic breast cancer. BRD4 also contributes to regulation of both cell cycle and transcription of oncogenes, HIV, and human papilloma virus (HPV). Despite its role in a broad range of biological processes, the precise molecular mechanism of BRD4 function remains unknown. We report that BRD4 is an atypical kinase that binds to the carboxyl-terminal domain (CTD) of RNA polymerase II and directly phosphorylates its serine 2 (Ser2) sites both in vitro and in vivo under conditions where other CTD kinases are inactive. Phosphorylation of the CTD Ser2 is inhibited in vivo by a BRD4 inhibitor that blocks its binding to chromatin. Our finding that BRD4 is an RNA polymerase II CTD Ser2 kinase implicates it as a regulator of eukaryotic transcription.