规格 | 价格 | 库存 | 数量 |
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10 mM * 1 mL in DMSO |
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1mg |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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Other Sizes |
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靶点 |
p110α (IC50 = 52 nM); p110β (IC50 = 166 nM); p110δ (IC50 = 116 nM); p110γ (IC50 = 262 nM); Vps34 (IC50 = 2.4 μM); p110α-H1047R (IC50 = 52 nM); p110α-E545K (IC50 = 99 nM); mTOR (IC50 = 4.6 μM)
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体外研究 (In Vitro) |
Buparlisib (NVP-BKM120) 对 I 类 PI3K(包括最常见的 p110α 突变体)表现出 50-300 nM 的活性。此外,NVP-BKM120 对 III 类和 IV 类 PI3K 的效果较差,分别在 2、5、>5 和 >25 μM 时检测到抑制 VPS34、mTOR、DNAPK 和 PI4K 的生化活性[1] 。 Buparlisib (NVP-BKM120) 诱导多发性骨髓瘤 (MM) 细胞凋亡,其方式取决于剂量和时间的推移。在浓度 ≥10 μM 时,buparlisib (NVP-BKM120) 在 24 小时内显着诱导所有测试的 MM 细胞系凋亡(与对照相比,P<0.05)。如果没有另外说明,以下实验将使用 ≥10 μM buparlisib (NVP-BKM120) 和 24 小时治疗周期。所有测试的 MM 细胞系均表现出对 buparlisib (NVP-BKM120) 治疗的剂量依赖性生长抑制。 Buparlisib (NVP-BKM120) IC50 在测试的 MM 细胞之间存在差异。处理 24 小时时,ARP-1、ARK 和 MM.1R 的 IC50 为 1 至 <10 μM,而 MM.1S 的 IC50 小于 <1 μM,U266 的 IC50 为 10 至 <10 μM。 <100μM,。总之,NVP-BKM120 治疗可抑制 MM 细胞的生长并导致其死亡,具体方式取决于剂量和时间长度[2]。
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体内研究 (In Vivo) |
在 A2780 异种移植肿瘤中,口服 3、10、30、60 和 100 mg/kg 剂量的 Buparlisib (NVP-BKM120) 会导致 pAKTSer473 的剂量依赖性调节。在3和10mg/kg的剂量下,观察到pAKTSer473的部分抑制,在30、60或100mg/kg的剂量下,观察到几乎完全的抑制。血浆和肿瘤药物暴露均与 pAKT 抑制(标准化为总 AKT)密切相关[1]。 Buparlisib (NVP-BKM120)(5 M/kg/天,持续 15 天)治疗小鼠的肿瘤负荷显着低于对照小鼠,如肿瘤体积 (P<0.05) 和循环人 kappa 链水平 (P<0.05) 所示。此外,NVP-BKM120治疗显着提高了荷瘤小鼠的存活率(P<0.05)[2]。
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酶活实验 |
BKM120 溶解在 DMSO 中,并以每孔 1.25 µL 的量直接分配到黑色 384 孔板中。要开始反应,请在测定缓冲液(10 mM Tris pH 7.5、5 mM MgCl2、20 mM NaCl、1 mM DTT 和 0.05% CHAPS)中添加 25 µL 10 nM PI3 激酶和 5 µg/mL 1-磷脂酰肌醇 (PI) )进入每个井。接下来,在测定缓冲液中添加 25 L 2 M ATP。在反应运行到耗尽 ATP 所需时间的大约 50% 后,添加 25 L KinaseGlo 溶液会停止反应。孵育 5 分钟后,检查停止的反应以确定是否仍然存在任何 ATP。
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细胞实验 |
A2780 细胞在补充有 10% FBS 的 DMEM 中培养。 L-谷氨酰胺、丙酮酸钠和抗生素。在黑壁透明底板中,将 1000 个细胞以每孔 100 uL 的密度接种在相同的培养基中,然后将细胞孵育 3 至 5 小时。将在 DMSO (20 mM) 中提供的 Buparlisib (NVP-BKM120) 在 DMSO 中进一步稀释(7.5 uL 20 mM Buparlisib 在 22.5 uL DMSO 中)。为了制备九个浓度,重复充分混合并添加 10 uL 至 20 uL DMSO 的过程。然后将稀释的 Buparlisib (NVP-BKM120) 溶液 (2 uL) 添加到细胞培养基 (500 uL) 中。将等量的该溶液 (100 uL) 倒在 96 孔板中的细胞顶部,然后在 37°C 下孵育三天,然后使用 Cell Titer Glo 进行显色。 Trilux 的发光读数用于确定细胞增殖是否受到抑制[1]。
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动物实验 |
Mice: The SCID (severe combined immunodeficiency) mouse model is a female, six to eight week old mouse. One million ARP-1 or MM.1S cells suspended in 50 μL phosphate-buffered saline (PBS) are subcutaneously injected into SCID mice in the right flank. DMSO/PBS or Buparlisib (NVP-BKM120) (5 μM per kg per day) are administered intraperitoneally to mice 15 days after the development of a palpable tumor (tumor diameter ≥5 mm). Each time a blood sample is taken, tumor sizes are also measured every five days. The size of the tumor and the presence of human kappa chain or lambda chain in the bloodstream are used to assess the burden of the tumor.
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参考文献 |
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分子式 |
C18H21F3N6O2
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分子量 |
410.3936
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精确质量 |
410.16781
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元素分析 |
C, 52.68; H, 5.16; F, 13.89; N, 20.48; O, 7.80
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CAS号 |
944396-07-0
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相关CAS号 |
Buparlisib Hydrochloride;1312445-63-8
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外观&性状 |
white solid powder
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SMILES |
NC1=NC=C(C2=NC(N3CCOCC3)=NC(N4CCOCC4)=C2)C(C(F)(F)F)=C1
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InChi Key |
CWHUFRVAEUJCEF-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C18H21F3N6O2/c19-18(20,21)13-9-15(22)23-11-12(13)14-10-16(26-1-5-28-6-2-26)25-17(24-14)27-3-7-29-8-4-27/h9-11H,1-8H2,(H2,22,23)
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化学名 |
5-[2,6-Di(4-morpholinyl)-4-pyrimidinyl]-4-(trifluoromethyl)-2-pyridinamine.
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别名 |
Buparlisib; BKM120; BKM-120; BKM 120; NVPBKM120; NVP BKM120; NV- BKM120
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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溶解度 (体外) |
DMSO: ~82 mg/mL (199.8 mM)
Water: <1 mg/mL (slightly soluble or insoluble) Ethanol: 2 mg/mL (4.87 mM) |
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溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (6.09 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 6: 0.5%CMC Na:6mg/mL Solubility in Formulation 7: 2.08 mg/mL (5.07 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. 1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL; 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果,工作液请现配现用! 6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
制备储备液 | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4367 mL | 12.1835 mL | 24.3671 mL | |
5 mM | 0.4873 mL | 2.4367 mL | 4.8734 mL | |
10 mM | 0.2437 mL | 1.2184 mL | 2.4367 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;
3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);
4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。
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) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
(2) 一定要按顺序加入溶剂 (助溶剂) 。
NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT04338399 | Recruiting | Drug: Buparlisib & Paclitaxel | Head and Neck Cancer | Adlai Nortye Biopharma Co., Ltd. | December 12, 2020 | Phase 3 |
NCT04975958 | Recruiting | Drug: AN2025 Drug: AN0025 |
Locally Advanced Solid Tumor | Adlai Nortye Biopharma Co., Ltd. | September 7, 2021 | Phase 1 |
NCT02128724 | Completed | Drug: BKM120 | Carcinoma, Non-Small-Cell Lung | University of Oxford | April 2013 | Phase 1 |
NCT01551030 | Completed | Drug: Buparlisib | Metastatic Transitional Cell Carcinoma of the Urothelium |
Memorial Sloan Kettering Cancer Center |
March 2012 | Phase 2 |
NCT02048787 | Completed | Drug: Buparlisib | Renal Impairment | Novartis Pharmaceuticals | March 2014 | Phase 1 |
Analysis ofbuparlisibsubstrate affinity for ABC transporters usingin vitrotransport assays.Sci Rep.2018 Jul 17;8(1):10784. td> |
Theimpact of P-gp and BCRP on the brain and tissue penetration of buparlisib. Buparlisibhas excellent intracranial target engagement and oral bioavailability.Sci Rep.2018 Jul 17;8(1):10784. td> |
NVP-BKM120inhibits cancer cell proliferation and induces apoptosis in a CCA mouse model.Oncol Lett.2018 Aug;16(2):1627-1633. td> |
Growth inhibition effect ofNVP-BKM120on CCA cell lines.Oncol Lett.2018 Aug;16(2):1627-1633. |