| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
The primary target of Terevalefim is the c-Met receptor tyrosine kinase, which is encoded by the MET gene. Terevalefim acts as a selective activator (agonist) of the c-Met receptor. By mimicking the activity of hepatocyte growth factor (HGF), it activates the c-Met signaling pathway, which is involved in cell proliferation, survival, and migration.
|
|---|---|
| ln Vitro |
Terevalefim (ANG-3777) at concentrations of 0–10 μM strongly prevents HUVEC from proliferating [2].
In vitro, Terevalefim (0-10 μM) significantly inhibits cancer cell proliferation in HUVECs. It activates the c-Met cascade, exhibiting c-Met-dependent and c-Met receptor activating effects. The compound's ability to modulate cell proliferation and survival makes it a crucial tool in cancer research. |
| ln Vivo |
Terevalefim (ANG-3777) inhibits cell engraftment, enhances proliferation, and promotes organ repair and function in animal models [1]. Terevalefim (ANG-3777, 40 mg/kg, IP) phosphorylates c-Met receptor [2].
In vivo, Terevalefim (40 mg/kg, IP) phosphorylates the c-Met receptor and selectively activates it without affecting other growth factor receptors. It inhibits cell engraftment, enhances proliferation, and promotes organ repair and function in animal models. It has been tested in clinical trials for acute kidney injury and delayed graft function. |
| Enzyme Assay |
The in vitro assay for Terevalefim involves measuring its effect on cell proliferation. Human umbilical vein epithelial cells (HUVECs) are treated with Terevalefim at concentrations of 0.44, 1.78, and 7.1 μM for 24 to 48 hours. Cell viability is assessed, and a dose-dependent inhibition of cell proliferation is observed.
|
| Cell Assay |
Cell viability assay [2]
Cell Types: human umbilical vein epithelial cells (HUVEC). Tested Concentrations: 0.44, 1.78 and 7.1 μM. Incubation Duration: 24 to 48 hrs (hours). Experimental Results: Dose-dependent inhibition of cell proliferation. |
| Animal Protocol |
Animal/Disease Models: SD rat[2].
Doses: 40 mg/kg. Management: IP injection, once. Experimental Results: Selective phosphorylation of c-Met receptor but not other growth factor receptors. In vivo animal studies for Terevalefim are conducted in SD rats. The compound is administered via intraperitoneal (IP) injection at a dose of 40 mg/kg. After a single administration, the selective phosphorylation of the c-Met receptor is measured, confirming target engagement. The compound's effects on organ repair and function are assessed in relevant disease models. Terevalefim has been studied in clinical trials for various indications. It was investigated in a Phase II proof-of-concept trial (NCT04459676) for its role in preventing and mitigating lung injury in COVID-19 patients. It has also been evaluated in clinical trial NCT02474667 for reducing the severity of delayed transplant renal function recovery in deceased donor kidney transplant recipients. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for Terevalefim are not detailed in the provided sources. The compound has a molecular weight of 176.24 g/mol and is soluble in DMSO. It appears as a white to light brown solid powder. Specific PK parameters such as half-life, bioavailability, and clearance have not been reported.
|
| Toxicity/Toxicokinetics |
Toxicity data for Terevalefim are not reported in the available sources. The compound has been evaluated in clinical trials for acute kidney injury and COVID-19, indicating that it has undergone safety assessments. Specific toxicological profiles are not provided in the supplier documentation.
|
| References | |
| Additional Infomation |
Terevalefim is currently undergoing clinical trial NCT02474667 (reducing the severity of delayed transplant renal function recovery in deceased donor kidney transplant recipients).
Mechanism of Action Terevalefim is a small molecule drug developed by Angion Biomedica that mimics the activity of hepatocyte growth factor (HGF). It works by activating the c-Met signaling pathway, exhibiting c-Met-dependent and c-Met receptor activating effects. Because it can activate repair pathways, it has been tested in clinical trials for acute kidney injury and delayed transplant renal function recovery. As of July 2020, Angion announced the initiation of a Phase II proof-of-concept trial (NCT04459676) to investigate the role of terevalefim in preventing and mitigating lung injury in COVID-19 patients. Terevalefim is an investigational HGF mimetic that selectively activates the c-Met receptor. It is being developed for the treatment of acute organ injury, such as delayed graft function and acute kidney injury. The compound has been tested in clinical trials and is available from commercial suppliers for research purposes. |
| Molecular Formula |
C9H8N2S
|
|---|---|
| Molecular Weight |
176.24
|
| Exact Mass |
180.072
|
| CAS # |
1070881-42-3
|
| PubChem CID |
5714038
|
| Appearance |
White to light brown solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Boiling Point |
288.0±29.0 °C at 760 mmHg
|
| Flash Point |
128.0±24.3 °C
|
| Vapour Pressure |
0.0±0.6 mmHg at 25°C
|
| Index of Refraction |
1.681
|
| LogP |
1.31
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
12
|
| Complexity |
170
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CSC(=C1)/C=C/C2=CC=NN2
|
| InChi Key |
FOHWAQGURRYJFK-ONEGZZNKSA-N
|
| InChi Code |
InChI=1S/C9H8N2S/c1-2-9(12-7-1)4-3-8-5-6-10-11-8/h1-7H,(H,10,11)/b4-3+
|
| Chemical Name |
5-[(E)-2-thiophen-2-ylethenyl]-1H-pyrazole
|
| 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 : ~100 mg/mL (~567.41 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (14.19 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 25.0 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: ≥ 2.5 mg/mL (14.19 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 25.0 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: ≥ 2.5 mg/mL (14.19 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 | 5.6741 mL | 28.3704 mL | 56.7408 mL | |
| 5 mM | 1.1348 mL | 5.6741 mL | 11.3482 mL | |
| 10 mM | 0.5674 mL | 2.8370 mL | 5.6741 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
