GSK 650394
(Synonyms: 2-环戊基-4-(5-苯基-1H-吡咯并[2,3-B]吡啶-3-基)苯甲酸) 目录号 : GC15441
GSK 650394是一种有效的选择性血清和糖皮质激素调节的激酶-1（SGK1）抑制剂，对SGK1和SGK2的IC50分别为62nM和103nM。
Cas No.:890842-28-1
Sample solution is provided at 25 µL, 10mM.
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GSK 650394 is an effective selective inhibitor of serum and glucocorticoid-regulated kinase-1 (SGK1), with IC50 values of 62nM and 103nM for SGK1 and SGK2, respectively [1]. SGK1 can enhance the survival ability, adhesion, invasiveness, mobility, and epithelial-to-mesenchymal transition ability of tumor cells [2]. GSK 650394 has the ability to prevent viral replication at concentrations that are non-toxic to cells [3-4].
In vitro, GSK 650394 (0.1-10μM; 24, 48h) significantly inhibits the growth of androgen-stimulated LNCaP cells and the increase in Nedd4-2 phosphorylation levels within the cells, and antagonizes the activity of SGK1 [1]. GSK 650394 (1, 3, and 10μM; 30min pretreatment) reduces the phosphorylation levels of NDRG1-Thr346/356/366 in hormone deprivation and insulin-stimulated cortical collecting duct (mpkCCD) cells in a concentration-dependent manner [5].
In vivo, GSK 650394 (1, 10, and 30μM; 10μL per rat; single intrathecal injection) dose-dependently alleviates the pain response induced by complete Freund's adjuvant (CFA) in rats, and inhibits the phosphorylation of SGK1, GluR1 transport, and protein-protein interactions [6]. GSK 650394 (10, 30mg/kg/day; 3 times a week for 8 weeks; i.p.) treatment dose-dependently improves the T-AOC, SOD levels, and bone density reduction in mice with osteoporosis induced by ovariectomy [7].
References:
[1] Sherk AB, Frigo DE, Schnackenberg CG, et al. Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic. Cancer Res. 2008;68(18):7475-7483.
[2] Cicenas J, Meskinyte-Kausiliene E, Jukna V, et al. SGK1 in cancer: Biomarker and drug target[J]. Cancers, 2022, 14(10): 2385.
[3] Alamares-Sapuay J G, Martinez-Gil L, Stertz S, et al. Serum-and glucocorticoid-regulated kinase 1 is required for nuclear export of the ribonucleoprotein of influenza A virus[J]. Journal of virology, 2013, 87(10): 6020-6026.
[4] Ye W, Tang S, Wang Y, et al. SGK1 mediates herpes simplex keratitis via the PI3K/SGK1/Wnt signaling pathways[J]. Cellular Signalling, 2025, 127: 111566.
[5] Mansley MK, Wilson SM. Effects of nominally selective inhibitors of the kinases PI3K, SGK1 and PKB on the insulin-dependent control of epithelial Na+ absorption. Br J Pharmacol. 2010;161(3):571-588.
[6] Peng HY, Chen GD, Hsieh MC, Lai CY, Huang YP, Lin TB. Spinal SGK1/GRASP-1/Rab4 is involved in complete Freund's adjuvant-induced inflammatory pain via regulating dorsal horn GluR1-containing AMPA receptor trafficking in rats. Pain. 2012;153(12):2380-2392.
[7] Jin L Y, Huo S C, Guo C, et al. GSK 650394 inhibits osteoclasts differentiation and prevents bone loss via promoting the activities of antioxidant enzymes in vitro and in vivo[J]. Oxidative Medicine and Cellular Longevity, 2022, 2022(1): 3458560.
GSK 650394是一种有效的选择性血清和糖皮质激素调节的激酶-1（SGK1）抑制剂，对SGK1和SGK2的IC50分别为62nM和103nM [1]。SGK1能够增强肿瘤细胞的存活能力、黏附性、侵袭性、移动性以及上皮向间质的转化能力 [2]。GSK 650394具有在对细胞无毒的浓度下阻止病毒复制的能力 [3-4]。
在体外，GSK 650394（0.1-10μM; 24, 48h）显著抑制雄激素刺激的LNCaP细胞的生长和细胞中Nedd4-2磷酸化水平的上升，并拮抗的SGK1活性[1]。GSK 650394（1, 3和10μM; 30min预处理)以浓度依赖性的方式降低了激素剥夺和胰岛素刺激的皮质收集管（mpkCCD）细胞中NDRG1-Thr346/356/366磷酸化的水平[5]。
在体内，GSK 650394（1, 10和30μM; 10μL/只; 单次鞘内注射）剂量依赖性地缓解了complete Freund’s adjuvant（CFA）诱导的大鼠疼痛反应，并且抑制SGK1的磷酸化、GluR1转运和蛋白质-蛋白质相互作用 [6]。GSK 650394（10, 30mg/kg/day; 每周3次，共8周; i.p.）治疗剂量依赖性地改善了卵巢切除诱导骨质流失小鼠的T-AOC、SOD水平和骨密度的降低 [7]。
| Kinase experiment [1]: | |
Preparation Method | Scintillation proximity assay (SPA)：SGK1 S422D (0.275μg/mL final concentration) or SGK2 (0.875μg/mL final concentration) were activated by PDK1 (1.1μg/mL final concentration) in a buffer consisting of 50mM Tris (pH 7.5), 0.1mM EGTA, 0.1mM EDTA, 10mM MgCl2, 0.1% β-mercaptoethanol, 1mg/mL BSA, and ATP (final concentration of 0.15mM) and incubated for 30min at 30°C. SGK2 was prepared exactly as described for SGK1, except it corresponded to the full-length protein. A solution containing biotinylated CROSStide peptide at a final concentration of 75μM and γ32P-ATP corresponding to 2×106cpm was prepared in the reaction buffer. In a 96-well plate, 5μL of GSK 650394 was added to 25μL of the activated enzyme mixture. To this, 20μL of the CROSStide mixture was added and incubated for 1h at room temperature. Next, 50μL of a 25mg/mL slurry of streptavidin-coated SPA beads in PBS with 0.1M EDTA, pH 8.0 was added. The plate was then sealed and centrifuged for 8min at 2000rpm, and the signal was detected by measuring for 30sec/well in a Packard TopCount NXT Scintillation Counter. The IC50 values of the inhibition of SGK1 and SGK2 activities by GSK 650394 were calculated from these data using GraphPad Prism 3 Software. |
Reaction Conditions | 10-10-10-5M; 1h |
Applications | GSK 650394 inhibited the enzymatic activities of SGK1 and SGK2 with IC50 values of 62nM and 103nM, respectively. |
| Cell experiment [1]: | |
Cell lines | LNCaP cells |
Preparation Method | LNCaP cells were plated at a density of 5,000 cells per well (for studies with GSK 650394) or 20,000 cells per well (for siRNA studies) in 96-well plates in 100μL PRF-RPMI 1640, supplemented with 8% CS-FBS, 0.1mM NEAA, and 1mM NaPyr. After a two-day incubation, cells were transfected with siRNAs as described above. Twenty μL of media was removed from each well and replaced with 20μL of the siRNA: Dharmafect-1 mix to obtain a final concentration of 50nM of siRNA. The siRNA transfection was repeated on day 6. At day three, cells were treated with hormone with or without GSK 650394 by removing 50μL of the media and replacing this with 50μL of PRF-RPMI 1640 with 8% CS-FBS, NEAA, NaPyr containing a 2X concentration of the appropriate hormone/inhibitor treatment. At days 5 and 7, the treatment was repeated. On the tenth day, the media was removed and the relative cell number was measured using the FluoReporter Blue assay. |
Reaction Conditions | 0.1-10μM; 24, 48h |
Applications | GSK 650394 significantly inhibits the growth of LNCaP cells mediated by androgens. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice (osteoporosis model) |
Preparation Method | Eight-week-old C57BL/6 mice were randomly divided into 4 groups (n = 5 for each group): Sham (only injected with saline), vehicle (OVX (ovariectomized) injected with saline), low-dose (OVX injected with 10 mg/kg GSK 650394), and high-dose (OVX injected with 30 mg/kg GSK 650394 injection). Mice were subjected to bilateral OVX or Sham surgery after a one-week adaptation feeding period. In brief, the skin was dissected bluntly until it reached the abdominal cavity after a 1-cm dorsal midline incision. The ovary’s protective adipose tissue in the abdominal cavity was seized and removed. Once the ovary was located, the uterine horns and vessels 0.5–1cm in front of it were tied off. The remainder of the tissue was then reinserted into the abdomen after the ovary and ligated adipose tissue had been removed. On sham-operated mice, the same surgical technique was carried out, with the exception of ovaries ligation and removal. GSK 650394 supplementation was based on intraperitoneally administration three times a week and a total for 8 weeks. At the end of eighth week, all mice were sacrificed using over dose pentobarbital to collect the tibial bone for micro-CT, histological analysis, and antioxidant enzyme activity test. |
Dosage form | 10, 30mg/kg/day; three times a week for a total of 8 weeks; i.p. |
Applications | GSK 650394 dose-dependently improved the T-AOC, SOD levels and bone density reduction in mice with osteoporosis induced by ovariectomy. |
References: | |
| Cas No. | 890842-28-1 | SDF | |
| 别名 | 2-环戊基-4-(5-苯基-1H-吡咯并[2,3-B]吡啶-3-基)苯甲酸 | ||
| 化学名 | 2-cyclopentyl-4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid | ||
| Canonical SMILES | C1CCC(C1)C2=C(C=CC(=C2)C3=CNC4=NC=C(C=C34)C5=CC=CC=C5)C(=O)O | ||
| 分子式 | C25H22N2O2 | 分子量 | 382.45 |
| 溶解度 | ≥ 19.1mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6147 mL | 13.0736 mL | 26.1472 mL |
| 5 mM | 0.5229 mL | 2.6147 mL | 5.2294 mL |
| 10 mM | 0.2615 mL | 1.3074 mL | 2.6147 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
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Quality Control & SDS
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- Purity: >99.50%
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