202592-23-2

Basic information

• Product Name: 6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, 4-(4-chlorophenyl)-2,3,9-triMethyl-, (6S)-
• Synonyms: 6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, 4-(4-chlorophenyl)-2,3,9-triMethyl-, (6S)-;JQ-1 (carboxylic acid);(+)-JQ1 (free acid)
• CAS NO: 202592-23-2
• Molecular Formula: C19H17ClN4O2S
• Molecular Weight: 400.88188
• Mol File: 202592-23-2.mol
• Article Data: 58

Chemical Properties

• Boiling Point: 661.6±65.0 °C(Predicted)
• Appearance: /
• Density: 1.51±0.1 g/cm3(Predicted)
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• PKA: 4.11±0.10(Predicted)
• CAS DataBase Reference: 6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, 4-(4-chlorophenyl)-2,3,9-triMethyl-, (6S)-(CAS DataBase Reference)
• NIST Chemistry Reference: 6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, 4-(4-chlorophenyl)-2,3,9-triMethyl-, (6S)-(202592-23-2)
• EPA Substance Registry System: 6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, 4-(4-chlorophenyl)-2,3,9-triMethyl-, (6S)-(202592-23-2)

Safety Data

• Hazardous Substances Data: 202592-23-2(Hazardous Substances Data)

Usage

Uses

(+)-JQ1 Carboxylic Acid is a selective inhibitor of BET bromodomains.

Upstream product

• 50508-66-2 (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone 
• 1268524-71-5 (-)-JQ₁ 
• 1268524-68-0 tert-butyl 2-(5-(4-chlorophenyl)-6,7-dimethyl-2-thioxo-2,3-dihydro-1H-thieno[2,3-e][1,4]diazepin-3-yl)acetate 
• 1268524-67-9 tert-butyl (S)-2-(5-(4-chlorophenyl)-6,7-dimethyl-2-oxo-2,3-dihydro-1H-thieno[2,3-e][1,4]diazepin-3-yl)acetate 
• 1268524-69-1 [4-(4-chlorophenyl)-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraazacyclopenta[e]azulen-6-yl]acetic acid tert-butyl ester 
• 1268524-65-7 (S)-tert-butyl 3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-((3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)amino)-4-oxobutanoate 
• 4640-66-8 p-chlorobenzoylacetonitrile 
• 33671-41-9 5-(4-chloro-phenyl)-6,7-dimethyl-1,3-dihydro-thieno[2,3-e][1,4]diazepin-2-one 
• 54861-99-3 glycine 3-(4-chloro-benzoyl)-4,5-dimethyl-thiophen-2-ylamide 
• 204587-29-1 C₁₅H₁₃Cl₂NO₂S 
• 166880-01-9 4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine 
• 1268524-70-4 (S)-tert-butyl 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)acetate 

Relevant articles and documents

Probing BRD Inhibition Substituent Effects in Bulky Analogues of (+)-JQ1

A series of bulky organometallic and organic analogues of the bromodomain (BRD) inhibitor (+)-JQ1 have been prepared. The most potent, N-[(adamantan-1-yl)methyl]-2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide, 2e, showed excellent potency with an KD=ca. 130 nm vs. BRD4(1) and a ca. 2-fold selectivity over BRD4(2) (KD=ca. 260 nm). Its binding to the first bromodomain of BRD4 was determined by a protein cocrystal structure.

COMPOUNDS HAVING BOTH EFFECTS OF BET BROMODOMAIN PROTEIN INHIBITION AND PD-L1 GENE REGULATION

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Harnessing the E3 Ligase KEAP1 for Targeted Protein Degradation

Proteolysis targeting chimeras (PROTACs) represent a new class of promising therapeutic modalities. PROTACs hijack E3 ligases and the ubiquitin-proteasome system (UPS), leading to selective degradation of the target proteins. However, only a very limited number of E3 ligases have been leveraged to generate effective PROTACs. Herein, we report that the KEAP1 E3 ligase can be harnessed for targeted protein degradation utilizing a highly selective, noncovalent small-molecule KEAP1 binder. We generated a proof-of-concept PROTAC, MS83, by linking the KEAP1 ligand to a BRD4/3/2 binder. MS83 effectively reduces protein levels of BRD4 and BRD3, but not BRD2, in cells in a concentration-, time-, KEAP1- and UPS-dependent manner. Interestingly, MS83 degrades BRD4/3 more durably than the CRBN-recruiting PROTAC dBET1 in MDA-MB-468 cells and selectively degrades BRD4 short isoform over long isoform in MDA-MB-231 cells. It also displays improved antiproliferative activity than dBET1. Overall, our study expands the limited toolbox for targeted protein degradation.

Traceless Staudinger ligation enabled parallel synthesis of proteolysis targeting chimera linker variants

A parallel, one-pot assembly approach to proteolysis targeting chimeras (PROTACs) is demonstrated utilizing activated esters generatedin situ, and traceless Staudinger ligation chemistry. The method described allows for rapid structure-activity relationship studies of PROTAC linker variants. Two previously studied systems, cereblon and BRD4 degraders, are examined as test cases for the synthetic method. The two related strategies to assemble PROTAC linker variants discussed can accommodate the chromotographic separations capabilities of labs of many sizes and incorporates commercially available degrader building blocks, thereby easing synthetic entry into PROTAC chemical space.