| Identification | Back Directory | [Name]
6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, N-[4-[[(2-aminophenyl)amino]carbonyl]phenyl]-4-(4-chlorophenyl)-2,3,9-trimethyl-, (6S)- | [CAS]
2614417-90-0 | [Synonyms]
6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, N-[4-[[(2-aminophenyl)amino]carbonyl]phenyl]-4-(4-chlorophenyl)-2,3,9-trimethyl-, (6S)- | [Molecular Formula]
C32H28ClN7O2S | [MOL File]
2614417-90-0.mol | [Molecular Weight]
610.13 |
| Chemical Properties | Back Directory | [density ]
1.44±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMF: 20 mg/ml; DMSO: 10 mg/ml | [form ]
A crystalline solid | [pka]
13.20±0.70(Predicted) | [color ]
white to beige |
| Hazard Information | Back Directory | [Description]
TW9 is a dual inhibitor of bromodomain 2 (BD2) in bromodomain-containing protein 4 (BRD4) and histone deacetylase 1 (HDAC1; IC50s = 0.074 and 0.29 μM, respectively).1 It is selective for BD2 over BD1 in BRD4 (IC50 = 0.72 μM) and for HDAC1 over HDAC2 (IC50 = 2.5 μM). TW9 (50 nM) induces apoptosis in, and inhibits proliferation of, MIA PaCa-2 pancreatic cancer cells. It induces cell cycle arrest at the G1 phase in HPAC pancreatic cancer cells when used at a concentration of 2 μM. TW9 acts synergistically with gemcitabine to reduce the viability of HPAC cells. | [Uses]
TW9 is a potent dual inhibitor simultaneously targeting BET and HDAC proteins with KDs of 0.069 μM, 0.231 μM for BRD4(1), BRD4(2), and an IC50 of 0.29 μM for HDAC1, respectively. TW9 is a newly generated adduct of the BET inhibitor (+)-JQ1 (HY-13030) and class I HDAC inhibitor CI994 (HY-50934). TW9 shows high potency in suppressing tumor growth in pancreatic ductal adenocarcinoma (PDAC). TW9 improves the efficacy of the chemotherapeutic agent Gemcitabine (HY-17026)[1]. | [IC 50]
BRD4(1): 0.069 μM (Kd); BRD4(2): 0.231 μM (Kd); HDAC1: 0.29 μM (IC50) | [References]
1. Zhang, X., Zegar, T., Weiser, T., et al. Characterization of a dual BET/HDAC inhibitor for treatment of pancreatic ductal adenocarcinoma Int. J. Cancer 147(10),2847-2861(2020). |
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| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
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