Bromodomain Inhibitor, (+)-JQ1 |
| 目录号 GC16531 |
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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Purity: >99.50%
- COA (Certificate Of Analysis)
- Datasheet
| Cell experiment:[1] | |
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Cell lines |
Human Leukemia OCI-AML3 (AML-M4 subtype, DNMT3A-R882, NPM1c-mutated, p53-wildtype) cell lines |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
0.25 μM JQ1 for 24 h incubation |
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Applications |
BRD4 bromodomain inhibitor JQ1 is highly active against human leukemia OCI-AML3 mutation lines such as nucleophosmin (NPM1) and DNA methyltransferase 3 (DNMT3A). JQ1 causes caspase 3/7-mediated apoptosis and DNA damage response in these cells. JQ1 prevented BRD4-mediated recruitment of p53 to chromatin targets following its activation in OCI-AML3 cells resulting in cell cycle arrest and apoptosis in a c-MYC-independent manner. |
| Animal experiment:[2] | |
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Animal models |
Male C57BL/6J (The Jackson Laboratory) and BALB/cJ (Charles River) mice, 6–8 wk of age |
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Dosage form |
10% (w:v) JQ1 solution in 2-hydroxypropyl-β-cyclodextrin solvent (Sigma-Aldrich); injected into the contralateral side of the abdomen |
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Applications |
JQ1 ablated cytokine production and blunted the “cytokine storm” in endotoxemic mice by reducing levels of IL-6 and TNF-α while rescuing mice from LPS-induced death. JQ1 benefited hyper-inflammatory conditions associated with high levels of cytokine production. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Stewart HJ1, Horne GA, Bastow S et al. BRD4 associates with p53 in DNMT3A-mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1. Cancer Med. 2013 Dec;2(6):826-35. [2]. Belkina AC1, Nikolajczyk BS, Denis GV. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses. J Immunol. 2013 Apr 1;190(7):3670-8. |
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Bromodomain Inhibitor, (+)-JQ1 is a potent and highly specific inhibitor for the BET (bromodomain and extra-terminal) family of bromodomains. (+)-JQ1 binds to BRD4 bromodomains 1 and 2 with Kd values of ~ 50 and 90 nM, respectively. The binding is competitive with acetyl lysine. (+)-JQ1 can be a useful chemical probe to investigate the role of BET bromodomains in the transcriptional regulation of oncogenesis.
JQ1 exhibited strong dose-and time- dependent inhibition of BRDT and could significantly diminish the activity of a close structural relative of BRDT. A close look at JQ1 bound BRDT confirmed that the acetyl-lysine recognition site of BRDT was blocked. [1]
JQ1 does not produce sedative or anxiolytic effects and is instead a potent and selective inhibitor of the bromodomain testis-specific protein BRDT [2], which is essential for chromatin remodeling during spermatogenesis. By blocking BRDT, JQ1 effectively blocks the production of sperm in the testes and consequently produces effective contraception, without the negative side effects associated with previously researched hormonal contraceptives for men.
References:
1. Matzuk, Martin M., et al. "Small-molecule inhibition of BRDT for male contraception." Cell 150.4 (2012): 673-684. 2. Filippakopoulos, P.; Qi, J.; Picaud, S.; Shen, Y.; Smith, W. B.; Fedorov, O.; Morse, E. M.; Keates, T. et al. (2010). "Selective inhibition of BET bromodomains". Nature 468 (7327): 1067–1073.
| Cas No. | 1268524-70-4 | SDF | |
| 别名 | N/A | ||
| 化学名 | (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 | ||
| Canonical SMILES | CC1=C(C)SC2=C1C(C3=CC=C(Cl)C=C3)=N[C@@H](CC(OC(C)(C)C)=O)C4=NN=C(C)N24 | ||
| 分子式 | C23H25ClN4O2S | 分子量 | 456.99 |
| 溶解度 | ≥ 22.8mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while. | ||
| Shipping Condition | Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request |
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| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % ddH2O | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Abstract
JQ1 induces 3/7-mediated apoptosis and DNA damage response in p53-wild-type (OCI)-AML3 cell lines where it possibly sensitizes AML cells to p53-mediated cell death. A mechanism has been proposed that JQ1 is activated in OCI-AML3 cells preventing BRD4-mediated recruitment of p53 to chromatin targets and eventually leading to cell cycle arrest and apoptosis in a c-MYC-independent manner.
Abstract
The affinities of acetylated histone tails and JQ1 to ten different BRD4 BD1 mutants were analyzed by several complementary biochemical and biophysical methods, in which W81, Y97, N140 and M149 play similarly important roles in the recognition of both.
Abstract
JQ1, an inhibitor of MYC expression, exhibits different inhibition in tumor cells where it decreased ~90% MYC transcription in BL cells and exhibited lesser inhibition in several non-BL cells possibly due to requirements of Brd4, transcription factors (such as Gdown1 and MED26) and other unknown cell specific factors.
Abstract
The critical role of BET proteins in macrophage inflammatory responses has been demonstrated in studies using small interfering RNA knockdown and JQ1 where Brad2 and brd4 doesn’t physically associated with the promoters of inflammatory cytokine genes in macrophages following the inhibition of BET by JQ1. JQ1 reduces the production of cytokine in vitro and weakens the “cytokine storm” in endotoxemic mice through decreasing IL-6 and TNF-α levels while rescuing mice from LPS-induced death.
Abstract
JQ1 dissociates Brd4 from the HIV promoter, synergizes with another latency activator prostratin and activates viral latency without inducing global T cell activation, which allow it and other closely related compounds as well as their antagonization of Brd4 to be used as effective agents/strategies to eliminating latent HIV in further investigations.