{{cart_num}}
My CartCAS：1217486-61-7
Storage：Powder:2-8℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year
Purity：≥98%
Appearance：White to yellow Solid
Qty：
Size：
| CAS | 1217486-61-7 |
| Name | Alpelisib |
| Molecular Formula | C19H22F3N5O2S |
| Molecular Weight | 441.47 |
| Solubility | Soluble in DMSO |
| Purity | ≥98% |
| Appearance | White to yellow Solid |
| Storage | Powder:2-8℃，2 years;Insolvent(Mother Liquid):-20℃，6 months;-80℃，1 year |
| Delivery Time | 1-2 Days |
| MDL | MFCD22417085 |
| SMILES | CC(N=C(S1)NC(N2CCC[C@H]2C(N)=O)=O)=C1C3=CC(C(C)(C(F)(F)F)C)=NC=C3 |
| InChIKey | STUWGJZDJHPWGZ-LBPRGKRZSA-N |
| InChI | InChI=1S/C19H22F3N5O2S/c1-10-14(11-6-7-24-13(9-11)18(2,3)19(20,21)22)30-16(25-10)26-17(29)27-8-4-5-12(27)15(23)28/h6-7,9,12H,4-5,8H2,1-3H3,(H2,23,28)(H,25,26,29)/t12-/m0/s1 |
| PubChem CID | 56649450 |
| Target Point | PI3K |
| Passage | PI3K/Akt/mTOR |
| Background | Alpelisib is a potent and selective PI3Kα inhibitor. |
| Biological Activity | Alpelisib 是有效，选择性的 PI3Kα 抑制剂，IC50 为5 nM[1-5]。 |
| IC50 | p110α:5nM;p110γ:250nM;p110δ:290nM;p110β:1200nM [1-5] |
| In Vitro | Alpelisib有效抑制2种最常见的PIK3CA体细胞突变(H1047R，E545K; IC50~4nM)。 Alpelisib有效抑制PI3Kα转化细胞中的Akt磷酸化(IC50 = 74±15 nM)，并显示PI3Kβ或PI3Kδ同种型转化细胞的抑制活性显著降低(与PI3Kα相比≥15倍)[2]。 Alpelisib通过阻断G0/G1期的细胞周期来减少细胞增殖，对HOS和MOS-J肿瘤细胞中的凋亡细胞死亡没有显著影响。在小鼠骨肉瘤的临床前模型中，Alpelisib显著降低肿瘤进展和肿瘤异位骨形成，如Ki67 +细胞减少和肿瘤血管形成所示。 Alpelisib在评估的所有细胞系中快速抑制P-AKT和P-mTOR的水平，证实了Alpelisib对骨肉瘤细胞的功能活性。处理72小时后，Alpelisib以剂量依赖性方式显著抑制所有骨肉瘤细胞系的细胞生长，IC50范围为6至15μM，IC90为24至42μM，72小时[3]。 |
| In Vivo | Alpelisib在大鼠，小鼠和狗中表现出优异的口服生物利用度，并且未显示对CYP450酶的任何显著抑制[1]。 Alpelisib抑制骨肉瘤的临床前小鼠模型中的肿瘤生长。将具有MOS-J肿瘤的C57Bl/6J(每组n = 6)随机化为对照(载体)或Alpelisib(12.5mg/kg或50mg/kg每天)[3]。 |
| Cell Experiment | 将两千个肿瘤细胞接种到96孔板中，第二天，用Alpelisib(1-50μM)处理细胞72小时。使用3'[1-(苯基氨基羰基)-3，4-四唑] - 双(4-甲氧基-6-硝基 -)苯磺酸水合物(XTT试剂测定试剂盒)的比色测定法测定细胞生长/活力。在490nm处读取吸光度。通过台盼蓝排除试验测定细胞活力;在治疗24和48小时后手动计数活细胞和非活细胞[3]。 |
| Animal Experiment | 大鼠[2]通过注射3×106至1×10 7个细胞或植入约50mg的肿瘤片段，在裸鼠或裸Rowett大鼠(Hsd：RH-Fox1rnu)中皮下或原位生长肿瘤异种移植物。携带肿瘤的动物小鼠用载体对照，Alpelisib或NVP-BKM120(po，每天)以所示剂量治疗。对于功效研究，当皮下植入的肿瘤达到约200mm 3并且每天50mg/kg用Alpelisib治疗时，招募携带肿瘤的动物。报告的反应是治疗最后一天肿瘤体积相对于第0天(治疗开始)的百分比变化。小鼠[3]通过吸入异氟烷/空气混合物(2％，1 L/min)麻醉5周龄雄性C57Bl/6J小鼠，然后肌肉注射1×106小鼠MOS-J骨肉瘤细胞。到胫骨，导致软组织肿瘤迅速增长，伴有继发性骨质侵入。肿瘤在8天后出现在注射部位并导致成骨细胞损伤，再现成骨细胞形式的人骨肉瘤。随机分配三组(每组n = 6)C57B1/6J以接受安慰剂或Alpelisib(口服给药，每日12.5-50mg/kg)。肿瘤细胞接种后1天开始预防性治疗。随机分配4组6个C57Bl/6J接受安慰剂(口服0.5％甲基纤维素和腹腔注射水)，Alpelisib(口服50mg/kg /天)，异环磷酰胺(腹腔注射30)在第一周期间三次mg/kg)，或Alpelisib(每天50mg/kg)和异环磷酰胺(30mg/kg，第一周三次)的组合。 |
| Data Literature Source | [1]. Furet P，et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3741-8. [2]. Fritsch C，et al. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014 May;13(5):1117-29. [3]. Gobin B，et al. BYL719，a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma. Int J Cancer. 2015 Feb 15;136(4):784-96. [4]. Venot Q，et al. Targeted therapy in patients with PIK3CA-related overgrowth syndrome. Nature. 2018 Jun;558(7711):540-546. [5]. Ding J，et al. Inhibition of BTF3 sensitizes luminal breast cancer cells to PI3Kα inhibition through the transcriptional regulation of ERα. Cancer Lett. 2018 Oct 10;440-441:54-63. |
| Unit | Bottle |
| Specification | 1mg 5mg 10mg |
是有效，选择性的 PI3Kα 抑制剂。
Remark：These protocols are for reference only. Solarbio does not independently validate these methods.
Note：
1. The products are all for scientific research use only. Do not use it for medical, clinical diagnosis or treatment, food and cosmetics, etc. Do not store them in ordinary residential areas.
2. For your safety and health, please wear laboratory clothes, disposable gloves and masks.
3. The experimental results may be affected by many factors, after-sale service is limited to the product itself and does not involve other compensation.
Sorry, there is no more information.
Manual Download
