Molibresib (I-BET762; GSK52576

Molibresib  (Synonyms: I-BET762; GSK525762; GSK525762A)

Molibresib (I-BET762; GSK525762) 是 BET 溴结构域 抑制剂，IC₅₀ 为32.5-42.5 nM。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。从产品的HNMR数据解析到生物活性数据，从客户的询价到产品的售后服务，我们拥有着完善的管理体系，从而保证我们的服务更加高效、准确。努力为中国的医药行业发展注入新的活力，我们将成为您研发工作值得信赖的伙伴。

生物活性    
Molibresib (I-BET762; GSK525762) is a BET bromodomain inhibitor with IC50 of 32.5-42.5 nM.

IC50 & Target    
IC50: 32.5-42.5 nM (BET)[1]

体外研究(In Vitro)    
Molibresib (I-BET 762) shows the highest affinity interaction with BET. Molibresib binds to the tandem bromodomains of BET with high affinity (dissociation constant Kd of 50.5-61.3 nM). Molibresib displaces, with high efficacy (half-maximum inhibitory concentration IC50 of 32.5-42.5 nM), a tetra-acetylated H4 peptide that had been pre-bound to tandem bromodomains of BET[1]. Molibresib has high affinity for BD1/BD2 domain of BRD2/3/4 proteins. Molibresib treatment leads to a reduction in the recruitment of all three proteins to chromatin[2]. Molibresib inhibits OPM-2 cell proliferation with IC50 of 60.15 nM[3].

体内研究(In Vivo)    
The antimyeloma activity of Molibresib (I-BET 762) is tested dosed orally in an in vivo systemic xenograft model generated by injecting OPM-2 cells into NOD-SCID mice. Daily oral doses of Molibresib up to 10 mg/kg and 30 mg/kg given every other day are well tolerated with no clear impact on body weight compared with vehicle control. The plasma hLC concentration is significantly reduced in mice treated with Molibresib[3].

分子量    
423.90

性状    
Solid

Formula    
C22H22ClN5O2

CAS 号    
1260907-17-2

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : 200 mg/mL (471.81 mM; Need ultrasonic)

1M HCl : 100 mg/mL (235.90 mM; ultrasonic and adjust pH to 1 with HCl)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.3590 mL    11.7952 mL    23.5905 mL
5 mM    0.4718 mL    2.3590 mL    4.7181 mL
10 mM    0.2359 mL    1.1795 mL    2.3590 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 2.5 mg/mL (5.90 mM); Clear solution

2.
请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

Solubility: ≥ 2.5 mg/mL (5.90 mM); Clear solution

3.
请依序添加每种溶剂： 5% DMSO    95% (20% SBE-β-CD in saline)

Solubility: ≥ 2.5 mg/mL (5.90 mM); Clear solution

4.
请依序添加每种溶剂： 1% DMSO    99% saline

Solubility: ≥ 0.5 mg/mL (1.18 mM); Clear solution
 

参考文献

[1]. Nicodeme E, et al. Suppression of inflammation by a synthetic histone mimic. Nature. 2010 Dec 23;468(7327):1119-23. [Content Brief] [2]. Asangani IA, et al. Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014 Jun 12;510(7504):278-82.  [Content Brief] [3]. Chaidos A, et al. Potent antimyeloma activity of the novel bromodomain inhibitors I-BET151 and I-BET762. Blood. 2014 Jan 30;123(5):697-705.  [Content Brief]