Buparlisib Hydrochloride 是一种 p

Buparlisib Hydrochloride  (Synonyms: BKM120 Hydrochloride; NVP-BKM120 Hydrochloride)

Buparlisib Hydrochloride (BKM120 Hydrochloride) 是一种 pan-class I PI3K 抑制剂，作用于p110α/p110β/p110δ/p110γ，IC₅₀ 分别为 52 nM/166 nM/116 nM/262 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。

生物活性    
Buparlisib Hydrochloride (BKM120 Hydrochloride) is a pan-class I PI3K inhibitor, with IC50 of 52 nM/166 nM/116 nM/262 nM for p110α/p110β/p110δ/p110γ, respectively.

体外研究
(In Vitro)    
Buparlisib (BKM120) exhibits 50-300 nM activity for class I PI3K’s, including the most common p110α mutants. Additionally, NVP-BKM120 exhibits lower potency against class III and class IV PI3K's, where 2, 5, >5, and >25 μM biochemical activity is observed for inhibition of VPS34, mTOR, DNAPK, and PI4K, respectively[1]. Buparlisib (BKM120) induces multiple myeloma (MM) cell apoptosis in both dose- and time-dependent manners. Buparlisib (BKM120) at concentrations ≥10 μM induces significant apoptosis in all tested MM cell lines at 24 h (P<0.05, compares with control). Therefore, 10 μM Buparlisib (BKM120) and 24-h treatment are chose in in the following experiments if not stated otherwise. Buparlisib (BKM120) treatment results in a dose-dependent growth inhibition in all tested MM cell lines. Buparlisib (BKM120) IC50 varies among tested MM cells. At 24 h treatment, IC50 for ARP-1, ARK, and MM.1R is between 1 and 10 μM, while IC50 for MM.1S is <1 μM, and IC50 for U266 is between 10 and 100 μM. In summary, Buparlisib (BKM120) treatment results in MM cell growth inhibition and apoptosis in dose- and time-dependent manners[2].

体内研究
(In Vivo)    
In A2780 xenograft tumors, oral dosing of Buparlisib (BKM120) at 3, 10, 30, 60, and 100 mg/kg results in a dose dependent modulation of pAKTSer473. Partial inhibition of pAKTSer473 is observed at 3 and 10 mg/kg, and near complete inhibition is observed at doses of 30, 60, or 100 mg/kg, respectively. Inhibition of pAKT (normalized to total AKT) tracked well with both plasma and tumor drug exposure[1]. Mice receiving Buparlisib (BKM120) (5 μM per kg per day for 15 days) treatment has significantly smaller tumor burdens as compare with control mice, which are measured as tumor volume (P<0.05) and level of circulating human kappa chain (P<0.05). In addition, Buparlisib (BKM120) treatment significantly prolongs the survival of tumor-bearing mice (P<0.05)[2].

分子量    
446.85

性状    
Solid

Formula    
C18H22ClF3N6O2

CAS 号    
1312445-63-8

中文名称    
布帕尼西盐酸盐

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

储存方式    
4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性数据    
In Vitro: 
DMSO : ≥ 50 mg/mL (111.89 mM)

* "≥" means soluble, but saturation unknown.

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.2379 mL    11.1894 mL    22.3789 mL
5 mM    0.4476 mL    2.2379 mL    4.4758 mL
10 mM    0.2238 mL    1.1189 mL    2.2379 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 (sealed storage, away from moisture)。-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 (5.59 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: ≥ 2.5 mg/mL (5.59 mM); Clear solution

3.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 2.5 mg/mL (5.59 mM); Clear solution
 

参考文献

[1]. Burger MT, et al. Identification of NVP-BKM120 as a Potent, Selective, Orally Bioavailable Class I PI3 Kinase Inhibitor for Treating Cancer. ACS Med Chem Lett. 2011 Aug 26;2(10):774-9.  [Content Brief] [2]. Zheng Y, et al. Novel phosphatidylinositol 3-kinase inhibitor NVP-BKM120 induces apoptosis in myeloma cells and shows synergistic anti-myeloma activity with dexamethasone. J Mol Med (Berl). 2012 Jun;90(6):695-706.  [Content Brief]