GSK2193874

製品コードS8367 バッチS836702

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C37H38BrF3N4O
分子量 691.62 CAS No. 1336960-13-4
Solubility (25°C)* 体外 DMSO 100 mg/mL (144.58 mM)
Ethanol (warmed with 50ºC water bath) 40 mg/mL (57.83 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO Corn oil

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 6.000mg/ml (8.68mM) Taking the 1 mL working solution as an example, add 50 μL of 120 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 GSK2193874 is an orally active, potent, and selective blocker of transient receptor potential vanilloid 4 (TRPV4) with IC50 values of 0.04 and 0.002 μM for hTRPV4 and rTRPV4, respectively.
in vitro GSK2193874 is profiled against TRP channels and is selective against TRPV1, TRPA1, TRPC3, TRPC6, and TRPM8 (IC50 > 25 μM)[1]. Treatment of human umbilical vein endothelial cells (HUVECs) with this compound dose-dependently prevents the cellular contraction and detachment induced by TRPV4 activation with GSK1016790[2].
in vivo The pharmacokinetic (PK) properties for GSK2193874 are evaluated in both rat and dog and found to have half-lives and oral exposure suitable for oral dosing in chronic animal models (Rat PK: iv CL = 7.3 mL/min/kg, po t1/2 = 10 h, %F =31. Dog PK: iv CL = 6.9 mL/min/kg, po t1/2 = 31 h, %F = 53). In addition, this compound shows no blood pressure or heart rate effect in rats when dose up to 30 mg/kg. It demonstrates to has the ability to improve pulmonary functions in a number of heart failure models[1]. In both acute and chronic HF models, this compound pretreatment inhibits the formation of pulmonary edema and enhanced arterial oxygenation. TRPV4 blockade with this chemical provides protection against the development of pulmonary edema and the resulting deficits in arterial oxygenation in HF models in vivo. This compound preserves endothelial cell integrity and inhibits endothelial TRPV4 currents while providing protection from formation of pulmonary edema in isolated lungs and in HF models[2].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Stably transfected hTRPV4 HEK cells (CG27) and HUVECs
濃度 1-30 nM(extracellularly); 0.03-10 uM(intracellularly)
反応時間 --
実験の流れ

TRPV4 HEK cells were pretreated with GSK2193874, extracellularly (1-30 nM) by application to the bathing solution, or intracellularly (0.03-10 uM) by inclusion in the pipette solution. Ramp currents were elicited between -60 and +60 mV and peak outward current at +60 mV was assessed after TRPV4 activation with GSK634775 (100 nM) added to the bath. In HUVECs, ramp currents were elicited between -80 and +80 mV and measured at + 60 mV, and the TRPV4 activator GSK1016790 (30 nM) was bath applied to activate TRPV4 followed by this compound (300 nM). 
動物実験 動物モデル Adult male Sprague-Dawley rats
投薬量 30 mg/kg
投与方法 via oral gavage

参考

  • http://pubs.acs.org/doi/abs/10.1021/acsmedchemlett.7b00094
  • https://pubmed.ncbi.nlm.nih.gov/23136043/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Magnetogenetics inspired by animal Magnetoreception: ΔTRPV4MagR as a novel magnetogenetic actuator enabling remote neuromodulation of brain circuits [ Brain Stimul, 2025, 18(5):1455-1469] PubMed: 40769384
Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement [ Int J Oral Sci, 2024, 16(1):3] PubMed: 38221531
Heat promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway [ iScience, 2023, 26(5):106749] PubMed: 37216091
Dental Pulp Stem Cell-Derived Exosomes Alleviate Mice Knee Osteoarthritis by Inhibiting TRPV4-Mediated Osteoclast Activation [ Int J Mol Sci, 2023, 24(5)4926] PubMed: 36902356
Endothelial Transient Receptor Potential Vanilloid 4 Channels Mediate Lung Ischemia-Reperfusion Injury [ Ann Thorac Surg, 2022, 113(4):1256-1264] PubMed: 33961815
TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome [ Neurosci Bull, 2021, 10.1007/s12264-021-00662-3] PubMed: 33761112
TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome [ Neurosci Bull, 2021, 37(7):905-920] PubMed: 33761112
Mechanical force modulates periodontal ligament stem cell characteristics during bone remodelling via TRPV4 [ Cell Prolif, 2020, 53(10):e12912] PubMed: 32964544
Regulation of mitochondrial fragmentation in microvascular endothelial cells isolated from the SU5416/hypoxia model of pulmonary arterial hypertension. [ Am J Physiol Lung Cell Mol Physiol, 2019, 317(5):L639-L652] PubMed: 31461316
Transient Receptor Potential Ion Channels Mediate Adherens Junctions Dysfunction in a Toluene Diisocyanate-Induced Murine Asthma Model [ Toxicol Sci, 2019, 168(1):160-170] PubMed: 30517707

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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