GSK2798745，一种临床候选药物，被鉴定为瞬时受体电位香草酸受体4（TRPV4）离子通道抑制剂，对人TRPV4和重组TRPV4的IC50值分别为1.8nM和1.6nM。
Cas No.:1419609-94-1
Sample solution is provided at 25 µL, 10mM.
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GSK2798745, a clinical candidate, was identified as an inhibitor of the transient receptor potential vanilloid 4 (TRPV4) ion channel with IC50 of 1.8 and 1.6nM for hTRPV4 and rTRPV4, respectively[1].
In vitro, GSK2798745 (0.3-100nM) inhibited TRPV4 channel activation in a dose-dependent manner following 1h treatment in 293T cells transfected with wild-type or mutant TRPV4[2].
In vivo, Treatment with GSK2798745 at a dose of 10mg/kg by twice daily intraperitoneal injections for 17 days can treat skeletal abnormalities caused by persistent activity of the mutant channel in Col2a1-Cre/Trpv4p.R594H mice[2].
References:
[1] Brooks CA, Barton LS, Behm DJ, et al. Discovery of GSK2798745: A Clinical Candidate for Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4). ACS Med Chem Lett. 2019;10(8):1228-1233.
[2] Nevarez L, Ismaili TK, Zieba J, et al. Small molecule inhibition rescues the skeletal dysplasia phenotype of Trpv4 mutant mice. JCI Insight. 2026;11(2):e182439.
GSK2798745，一种临床候选药物，被鉴定为瞬时受体电位香草酸受体4（TRPV4）离子通道抑制剂，对人TRPV4和重组TRPV4的IC50值分别为1.8nM和1.6nM[1]。
体外实验中，用野生型或突变型TRPV4转染293T细胞，GSK2798745（0.3-100nM）经1小时处理后，以剂量依赖的方式抑制了TRPV4通道的激活[2]。
体内实验中，对Col2a1-Cre/Trpv4p.R594H小鼠，以10mg/kg的剂量，每日两次腹腔注射GSK2798745，持续17天，可以治疗由突变通道持续活性引起的骨骼异常[2]。
| Cell experiment [1]: | |
Cell lines | 293T cells transfected with wild-type or mutant TRPV4 plasmids |
Preparation Method | HEK293 cells were transiently transfected with human TRPV4 WT or mutation constructs and pretreated with a range of concentrations (0.3-100nM) of GSK2798745 for 1 hour. Calcium flux was measured using a FLIPR-based calcium flux assay. |
Reaction Conditions | 0.3-100nM; 1h |
Applications | The activation activity of the mutant channels was inhibited by GSK2798745 in a dose-dependent manner. Compared with cells expressing wild-type TRPV4, all mutant channels had higher intracellular calcium levels, and these levels were inhibited by GSK2798745. |
| Animal experiment [1]: | |
Animal models | Col2a1-Cre/Trpv4p.R594H mice |
Preparation Method | Mutant mice were treated for 17 days by twice daily i.p. injections of GSK2798745. The treated mice were then subjected to radiological and morphological examinations. |
Dosage form | 10mg/kg; twice daily; 14-17d; i.p. |
Applications | GSK2798745 inhibitor improved the qualitative appearance of the vertebral bodies and proximal tibiae. Proliferating and hypertrophic chondrocytes were morphologically normal in the treated mice and normally expressed Sox9 and Col10a1, respectively. |
References: | |
| Cas No. | 1419609-94-1 | SDF | |
| Canonical SMILES | N#CC1=CC=C2N=CN(C[C@](CCC3)(C)C[C@@]43CN(C5=NC=C(C(C)(O)C)N=C5)C(O4)=O)C2=C1 | ||
| 分子式 | C25H28N6O3 | 分子量 | 460.53 |
| 溶解度 | DMSO: 250 mg/mL (542.85 mM) | 储存条件 | Store at -20°C,protect from light |
| 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 | 2.1714 mL | 10.8571 mL | 21.7141 mL |
| 5 mM | 434.3 μL | 2.1714 mL | 4.3428 mL |
| 10 mM | 217.1 μL | 1.0857 mL | 2.1714 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.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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