| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
GSK2798745 targets the transient receptor potential vanilloid 4 (TRPV4) ion channel, a calcium-permeable non-selective cation channel involved in mechanosensation and osmoregulation. The compound blocks TRPV4 with high potency: IC₅0 = 1.8 nM for human TRPV4 and 1.6 nM for rat TRPV4. TRPV4 is implicated in pulmonary edema, and its blockade may reduce fluid accumulation in the lungs.
|
|---|---|
| ln Vitro |
Human umbilical vein endothelial cells' (HUVEC) TRPV4 agonist-induced decrease in impedance is inhibited by GSK2798745 [3].
In vitro, GSK2798745 demonstrates potent blockade of TRPV4 with IC₅0 values of 1.8 nM for human TRPV4 and 1.6 nM for rat TRPV4. The compound is highly selective for TRPV4 over other ion channels. It is a first-in-class TRPV4 blocker with potent activity in vitro. Detailed cellular activity data are not extensively documented in the available literature. |
| ln Vivo |
In rats, TRPV4 agonist-mediated pulmonary edema is inhibited in a dose-dependent manner by GSK2798745 [3].
In vivo, GSK2798745 has demonstrated efficacy in models of pulmonary edema associated with congestive heart failure. The compound is orally active, making it suitable for oral administration in research settings. It is used in research for the treatment of pulmonary edema. Further detailed in vivo efficacy data are available in the scientific literature. |
| Enzyme Assay |
The in vitro ion channel assay for TRPV4 uses cells expressing human or rat TRPV4. Patch-clamp electrophysiology is performed to measure TRPV4 currents in response to TRPV4 agonists (such as GSK1016790A or hypotonic stress) in the presence of varying concentrations of GSK2798745. IC₅0 values are calculated from dose-response curves. Calcium imaging assays using fluorescent calcium indicators (such as Fura-2 or Fluo-4) may also be used to measure TRPV4-mediated calcium influx.
|
| Cell Assay |
For in vitro cell-based assays, cells expressing TRPV4 (such as primary endothelial cells or transfected cell lines) are cultured and treated with GSK2798745 at various concentrations. TRPV4-mediated calcium influx is measured using fluorescent calcium indicators in response to TRPV4 activation. Cell viability is assessed to confirm that the compound is not cytotoxic. Experiments are typically performed in triplicate with appropriate positive and negative controls.
|
| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat TRPV4-mediated pulmonary edema [3]
Doses: 0, 16, 50 or 150 ng/kg per minute 0, 16, 50 or 150 ng/kg per minute; 60 minutes Experimental Results: Inhibition of pulmonary edema Complete inhibition of edema formation was observed at the highest dose tested, where the ratio of basal lung wet weight to body weight remained at control levels (LW/BW=4.21). In vivo animal studies for GSK2798745 typically involve rodent models of pulmonary edema or heart failure. The compound is administered orally at various doses. Pulmonary edema is induced by volume overload or other methods, and lung wet/dry weight ratio is measured to assess edema severity. Hemodynamic parameters may be monitored. Target engagement is confirmed by assessing TRPV4 expression or activity in lung tissue. Efficacy is evaluated by reduction in pulmonary edema. |
| ADME/Pharmacokinetics |
GSK2798745 is orally active with good bioavailability. The compound has molecular weight 460.53 and molecular formula C2₅H2₈N₆O3. It is soluble in DMSO and typically formulated for oral administration in research settings. The compound is available as a 10 mM solution in DMSO. Further detailed PK parameters (half-life, Cmax, AUC) are not extensively documented in the available literature. Storage at -20degC is recommended.
|
| Toxicity/Toxicokinetics |
Toxicological data for GSK2798745 are not well characterized in the public domain. As a research chemical, standard safety precautions should be observed. The compound is for laboratory use only and not intended for human therapeutic applications. TRPV4 blockers as a class may have potential effects on vascular function and fluid homeostasis. Comprehensive toxicity profiling would be required for therapeutic development.
|
| References |
|
| Additional Infomation |
GSK2798745 is being studied in the clinical trial NCT03372603 (a study evaluating the efficacy and side effects of GSK2798745 in patients with chronic cough).
GSK2798745 (CAS# 1419609-94-1) is a first-in-class, highly potent, selective, orally active TRPV4 ion channel blocker. It has IC₅0 values of 1.8 nM for hTRPV4 and 1.6 nM for rTRPV4. The compound is used in research for pulmonary edema associated with congestive heart failure and is not approved for clinical use. |
| Molecular Formula |
C₂₅H₂₈N₆O₃
|
|---|---|
| Molecular Weight |
460.53
|
| Exact Mass |
460.222
|
| CAS # |
1419609-94-1
|
| PubChem CID |
71227359
|
| Appearance |
Off-white to light yellow solid powder
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
682.1±65.0 °C at 760 mmHg
|
| Flash Point |
366.3±34.3 °C
|
| Vapour Pressure |
0.0±2.2 mmHg at 25°C
|
| Index of Refraction |
1.680
|
| LogP |
1.76
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
34
|
| Complexity |
844
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
C[C@@]1(CCC[C@]2(C1)CN(C(=O)O2)C3=NC=C(N=C3)C(C)(C)O)CN4C=NC5=C4C=C(C=C5)C#N
|
| InChi Key |
URCMKDJBULWNAI-DQEYMECFSA-N
|
| InChi Code |
InChI=1S/C25H28N6O3/c1-23(2,33)20-11-28-21(12-27-20)31-15-25(34-22(31)32)8-4-7-24(3,13-25)14-30-16-29-18-6-5-17(10-26)9-19(18)30/h5-6,9,11-12,16,33H,4,7-8,13-15H2,1-3H3/t24-,25-/m0/s1
|
| Chemical Name |
1-(((5S,7S)-3-(5-(2-Hydroxypropan-2-yl)pyrazin-2-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile
|
| Synonyms |
GSK-2798745 GSK2798745 GSK 2798745
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~542.85 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.52 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 20.8 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: ≥ 2.08 mg/mL (4.52 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 20.8 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: ≥ 2.08 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1714 mL | 10.8571 mL | 21.7141 mL | |
| 5 mM | 0.4343 mL | 2.1714 mL | 4.3428 mL | |
| 10 mM | 0.2171 mL | 1.0857 mL | 2.1714 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
