| 规格 | 价格 | 库存 | 数量 |
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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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| 体外研究 (In Vitro) |
在细胞活力实验中，S-Gboxin 对原发性胶质母细胞瘤高通量肿瘤球 (HTS) 细胞的 IC₅₀ 为 470 nM。[1]
蛋白质印迹分析显示，S-Gboxin（1 μM，12 小时）与其母体化合物 Gboxin 一样，能上调 HTS GBM 细胞中 ATF4 的表达并抑制磷酸化 S6 (p-S6) 的水平。[1] |
|---|---|
| 体内研究 (In Vivo) |
S-Gboxin 保留了出色的代谢稳定性、改善的血浆稳定性以及适合体内研究的 PK 特性。腹腔注射 S-Gboxin（10 mg/kg/天）可抑制体内胶质母细胞瘤 (GBM) 的生长 [1]。
S-Gboxin 抑制了裸鼠中小鼠 GBM（HTS 细胞）同种移植瘤的生长。在皮下侧腹植入细胞 3 天后开始，每日腹腔注射 (IP) S-Gboxin（10 mg/kg/天），与溶剂对照组相比，显著降低了肿瘤体积。处理后的肿瘤显示细胞密度降低、增殖减少（Ki67阳性细胞）以及高级别胶质瘤标志物（GFAP 和 Olig2）表达下降。 在另一项于植入后 14 天开始治疗的实验中，S-Gboxin 同样抑制了肿瘤生长并延长了小鼠的生存期。[1] S-Gboxin 也抑制了皮下植入免疫缺陷小鼠体内的原发性人 GBM 患者来源异种移植 (PDX) 细胞（ts1156）的生长。在植入后 3 天开始每日 IP 给药（10 mg/kg/天），导致肿瘤生长显著减弱和细胞密度降低。[1] 对于颅内肿瘤，在原位移植原发性小鼠 GBM 细胞两周后，开始通过连接至颅内导管的皮下微型泵局部递送 S-Gboxin（2.16 µg/天/只）。该治疗抑制了肿瘤生长，减少了出血和细胞密度，并降低了增殖和胶质瘤标志物的表达。[1] S-Gboxin 还在两个独立的正位患者来源异种移植 (PDX) 模型（PDX-170620 和 PDX-170404）中进行了测试。在肿瘤建立后通过微型泵局部给药，抑制了 GBM PDX 的生长，表现为与溶剂对照组相比，治疗小鼠的一般健康状况改善、肿瘤细胞密度降低、增殖减少以及 GBM 标志物表达下降。[1] |
| 细胞实验 |
进行细胞活力实验以确定细胞对 S-Gboxin 的敏感性。用递增剂量的化合物处理细胞 96 小时，并使用 Cell-Titer-Glo® 发光细胞活力测定方案评估活力。IC₅₀ 值从剂量反应曲线计算得出。[1]
对于分子分析，用 S-Gboxin（例如，1 μM）处理细胞指定时间（例如，12 小时）。然后裂解细胞并提取蛋白质，进行蛋白质印迹分析以检测 ATF4 和磷酸化 S6 等标志物的变化。[1] |
| 动物实验 |
Animal/Disease Models: Female nude mice (6 to 9 weeks) [1]
Doses: 10 mg/kg/day Route of Administration: intraperitoneal (ip) injection; daily; 3 or 14 days Experimental Results: Caused Dramatically attenuated growth and Cell density decreases. Subcutaneous Allograft Model (Mouse GBM): 10^5 primary mouse GBM (HTS) cells were injected subcutaneously into the flanks of nude mice. Mice were treated daily via intraperitoneal (IP) injection with either vehicle or S-Gboxin at a dose of 10 mg/kg/day. Treatment commenced either 3 days or 14 days after cell implantation. Tumor dimensions were measured every 2 days to calculate volume (Width x Length x Height). Mice were monitored for survival or sacrificed for tumor analysis.[1] Subcutaneous Xenograft Model (Human GBM PDX): 2×10^5 primary human GBM PDX cells (ts1156) were mixed with Matrigel and injected subcutaneously into the flanks of immunocompromised mice. Daily IP treatment with vehicle or S-Gboxin (10 mg/kg/day) began 3 days after implantation. Tumor growth was monitored by measuring volume every 2 days.[1] Intracranial Orthotopic Models: For local delivery, primary mouse GBM cells or freshly harvested human GBM PDX tumor cells were orthotopically implanted into the brains of mice. After a recovery/tumor establishment period (2 weeks for mouse cells, 2-4 weeks for PDX models), an intracranial catheter connected to a subcutaneous osmotic minipump was implanted at the injection site. The minipumps delivered vehicle or S-Gboxin continuously. For the mouse GBM model, the delivery rate was 2.16 µg of S-Gboxin per day per mouse. Mice were monitored for symptoms and sacrificed for brain analysis.[1] |
| 药代性质 (ADME/PK) |
S-Gboxin was identified from structure-activity relationship (SAR) studies as a functional analog with improved metabolic stability and pharmacokinetic properties suitable for in vivo studies.
Plasma pharmacokinetic (PK) data indicated that S-Gboxin had enhanced plasma stability compared to the original Gboxin compound. Tumor PK data showed that S-Gboxin was detectable in tumors after administration.[1] Specific parameters such as half-life, Cmax, AUC, oral bioavailability, absorption, distribution, metabolism, and excretion details were not provided in the main text or extended data figures for S-Gboxin.[1] |
| 毒性/毒理 (Toxicokinetics/TK) |
In in vivo studies, mice treated daily with S-Gboxin (10 mg/kg/day, IP) for up to 32 days did not exhibit weight loss compared to vehicle-treated controls.
No overt signs of general health deficits were detected in treated mice during the study periods.[1] Specific toxicity parameters such as LD₅₀, hepatotoxicity, nephrotoxicity, drug-drug interactions, or plasma protein binding were not reported.[1] |
| 参考文献 | |
| 其他信息 |
S-Gboxin is a pharmacologically stable analog of Gboxin, a novel small-molecule inhibitor of oxidative phosphorylation (OxPhos) that selectively targets glioblastoma and other cancer cells.
The activity of S-Gboxin is linked to the heightened proton gradient across the mitochondrial inner membrane in cancer cells. Its positive charge facilitates accumulation within the mitochondrial matrix, where it interacts with and inhibits OxPhos complexes, particularly Complex V (F0F1 ATP synthase). Resistance to Gboxin/S-Gboxin in normal wild-type cells is mediated by a functional mitochondrial permeability transition pore (mPTP), which regulates matrix pH and limits compound accumulation. Many cancer cells, including GBM, exhibit blunted mPTP activity, making them selectively sensitive. Primary cultures established from residual S-Gboxin-treated tumors retained sensitivity to both Gboxin and S-Gboxin, suggesting that treatment failure in vivo was likely due to inefficient drug access over time rather than acquired resistance.[1] |
| 分子式 |
C27H32F3IN2O2
|
|---|---|
| 分子量 |
600.454870223999
|
| 精确质量 |
600.146
|
| 元素分析 |
C, 54.01; H, 5.37; F, 9.49; I, 21.13; N, 4.67; O, 5.33
|
| CAS号 |
2101317-21-7
|
| 相关CAS号 |
2101317-20-6 (cation);2101317-21-7 (iodide);
|
| PubChem CID |
137628665
|
| 外观&性状 |
Solid powder
|
| tPSA |
35.1
|
| 氢键供体(HBD)数目 |
0
|
| 氢键受体(HBA)数目 |
6
|
| 可旋转键数目(RBC) |
6
|
| 重原子数目 |
35
|
| 分子复杂度/Complexity |
700
|
| 定义原子立体中心数目 |
3
|
| SMILES |
C[C@@H]1CC[C@H]([C@@H](C1)OC(=O)CN2C3=CC=CC=C3[N+](=C2C4=CC(=CC=C4)C(F)(F)F)C)C(C)C.[I-]
|
| InChi Key |
DCAJNAWCJSUZDG-DZJKTSMVSA-M
|
| InChi Code |
InChI=1S/C27H32F3N2O2.HI/c1-17(2)21-13-12-18(3)14-24(21)34-25(33)16-32-23-11-6-5-10-22(23)31(4)26(32)19-8-7-9-20(15-19)27(28,29)30;/h5-11,15,17-18,21,24H,12-14,16H2,1-4H3;1H/q+1;/p-1/t18-,21+,24-;/m1./s1
|
| 化学名 |
3-(2-(((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)oxy)-2-oxoethyl)-1-methyl-2-(3-(trifluoromethyl)phenyl)-1H-benzo[d]imidazol-3-ium iodide
|
| 别名 |
S-Gboxin; S Gboxin
|
| 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 注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。 |
| 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 (体外实验) |
DMSO : ~93.33 mg/mL (~155.43 mM)
H2O : ~1 mg/mL (~1.67 mM) |
|---|---|
| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 9.33 mg/mL (15.54 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 93.3 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。 *生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。 配方 2 中的溶解度: ≥ 9.33 mg/mL (15.54 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 例如，若需制备1 mL的工作液，可将 100 μL 93.3mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，混匀。 *20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。 View More
配方 3 中的溶解度: ≥ 9.33 mg/mL (15.54 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 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 | 1.6654 mL | 8.3271 mL | 16.6542 mL | |
| 5 mM | 0.3331 mL | 1.6654 mL | 3.3308 mL | |
| 10 mM | 0.1665 mL | 0.8327 mL | 1.6654 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) 。
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