规格 | 价格 | 库存 | 数量 |
---|---|---|---|
10 mM * 1 mL in DMSO |
|
||
2mg |
|
||
5mg |
|
||
10mg |
|
||
25mg |
|
||
50mg |
|
||
100mg |
|
||
250mg |
|
||
500mg |
|
||
Other Sizes |
|
体外研究 (In Vitro) |
Sonidegib (NVP-LDE225) 对主要的人类 CYP450 药物代谢酶的 IC50 值超过 10 μM[1]。当单独给药或与尼罗替尼联合给药时,索尼吉布 (LDE225)(一种正在临床研究的小分子 SMO 抑制剂)可抑制 CD34+ 慢性期 (CP)-慢性粒细胞白血病 (CML) 细胞中的 Hh 通路,从而减少CML 白血病干细胞 (LSC) 的自我更新。与环巴明类似,sonidegib 直接与 SMO 相互作用,降低下游 Hh 信号靶标的表达。无血清培养基 (SFM)±Sonidegi 用于在 6、24 和 72 小时 (h) 期间培养原代 CD34+ CP-CML 细胞。暴露于 10 nM 的 Sonidegib 后; 0.78 倍和 100 nM; GLI1 在 72 小时时分别显着下调 0.73 倍 (p<0.01),但整个生物样品中存在多样性[2]。
|
||
---|---|---|---|
体内研究 (In Vivo) |
Sonidegib (NVP-LDE225) 的 pKa 为 4.2,使其成为弱碱,在水中的溶解度相对较低。口服二磷酸盐悬浮液10天后,在皮下Ptch+/-p53-/-髓母细胞瘤同种异体移植小鼠模型中观察到索尼吉布剂量相关的抗肿瘤活性。 Sonidegib 在 5 mg/kg/天 qd 的剂量下表现出显着的肿瘤生长抑制作用,与载体对照相比,相应的 T/C 值为 33% (p<0.05)。当以 10 和 20 mg/kg/天每日一次的剂量给药时,Sonidegib 分别提供 51% 和 83% 的消退[1]。二级受体小鼠被移植来自一组接受治疗的小鼠的骨髓和脾细胞。将接受 Sonidegib (LDE225)+Nilotinib 治疗的小鼠移植的骨髓 (BM) 或脾细胞与单独使用 Sonidegib 或 Nilotinib 进行比较,后者可减少继发受体中白血病的发生并降低白细胞计数 (WCC)[2]。
|
||
动物实验 |
|
||
参考文献 |
[1]. Pan S, et al. Discovery of NVP-LDE225, a Potent and Selective Smoothened Antagonist. ACS Med Chem Lett. 2010 Mar 16;1(3):130-4.
[2]. Irvine DA, et al. Deregulated hedgehog pathway signaling is inhibited by the smoothened antagonist LDE225 (Sonidegib) in chronic phase chronic myeloid leukaemia. Sci Rep. 2016 May 9;6:25476 |
分子式 |
C26H32F3N3O11P2
|
---|---|
分子量 |
681.49
|
CAS号 |
1218778-77-8
|
相关CAS号 |
Sonidegib;956697-53-3
|
SMILES |
N1(C[C@H](C)O[C@H](C)C1)C1=CC=C(C=N1)NC(=O)C1C=CC=C(C2C=CC(=CC=2)OC(F)(F)F)C=1C.P(O)(O)(O)=O.P(O)(O)(O)=O
|
别名 |
Sonidegib phosphate; Sonidegib diphosphate; LDE 225 phosphate; LDE 225 diphosphate;LDE-225 phosphate; LDE225 phosphate; LDE-225 diphosphate; LDE225 diphosphate; NVP-LDE225 diphosphate; NVP LDE-225 diphosphate; NVP-LDE225 phosphate; NVP LDE-225 phosphate; NVP LDE225 phosphate; Erismodegib phosphate; Erismodegib diphosphate; trade name of Odomzo
|
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)
|
溶解度 (体外) |
|
|||
---|---|---|---|---|
溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.67 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 (3.67 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 (3.67 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: 0.2% Tween80 + and 0.5% methyl cellulose Solubility in Formulation 5: 5 mg/mL (7.34 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication (<60°C). 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 | 1.4674 mL | 7.3369 mL | 14.6737 mL | |
5 mM | 0.2935 mL | 1.4674 mL | 2.9347 mL | |
10 mM | 0.1467 mL | 0.7337 mL | 1.4674 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 | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT02254551 | Terminated Has Results | Drug: LDE225 Drug: Bortezomib |
Multiple Myeloma | SCRI Development Innovations, LLC | January 2015 | Phase 2 |
NCT04066504 | Active, not recruiting | Drug: sonidegib | Basal Cell Carcinoma | Sun Pharmaceutical Industries Limited | March 11, 2019 | |
NCT02086513 | Terminated | Drug: LDE225 | Graft Versus Host Disease | Massachusetts General Hospital | April 2014 | Phase 1 |
NCT04007744 | Recruiting | Biological: Pembrolizumab Drug: Sonidegib |
Clinical Stage III Cutaneous Melanoma AJCC v8 Clinical Stage III Gastric Cancer AJCC v8 |
Mayo Clinic | February 13, 2020 | Phase 1 |
Antitumor activity in an orthotopic Ptch+/−p53−/−medulloblastoma allograft model in nude mice upon treatment with5mdiphosphate salt dosed at 40 mg/kg/day po bid or vehicle at equal dose volume.ACS Med Chem Lett. 2010 Jun 10; 1(3): 130–134. th> |
---|
Antitumor activity upon treatment with5mdiphosphate salt or vehicle in a Ptch+/−p53−/− medulloblastoma subcutaneous allograft model in nude mice.ACS Med Chem Lett. 2010 Jun 10; 1(3): 130–134. td> |
Gli1 mRNA inhibition (open circle), tumor PK (filled squares), and plasma PK (filled triangles) in Ptch+/−p53−/−medulloblastoma model after treatment with5m (Sonidegib, or erismodegib, LDE225, NVP-LDE225).ACS Med Chem Lett. 2010 Jun 10; 1(3): 130–134. td> |