| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
K41498 TFA targets the corticotropin-releasing factor type 2 receptor (CRF2), with high selectivity for the CRF2alpha and CRF2beta subtypes. It exhibits Ki values of 0.66 nM for human CRF2alpha, 0.62 nM for human CRF2beta, and 425 nM for human CRF1, demonstrating approximately 700-fold selectivity for CRF2 over CRF1. The peptide functions as a competitive antagonist, blocking the binding of endogenous ligands such as urocortin 1, urocortin 2, and urocortin 3.
|
|---|---|
| ln Vitro |
In cell-free assays, K41498 TFA binds to CRF2alpha and CRF2beta with high affinity. Binding is measured by competitive radioligand displacement using [125I]-sauvagine or [125I]-urocortin. The peptide shows negligible binding to CRF1 (Ki 425 nM). It also shows no significant activity at other GPCRs in broad panel screening. This exceptional selectivity makes K41498 TFA a valuable pharmacological tool for dissecting CRF2-specific functions.
|
| ln Vivo |
In cell-based functional assays using CHO or HEK293 cells expressing human CRF2alpha or CRF2beta, K41498 TFA potently inhibits sauvagine- or urocortin-stimulated cAMP accumulation. The IC50 for inhibiting agonist-induced cAMP production is in the low nanomolar range. The peptide has no intrinsic agonist activity at CRF2 receptors. The inhibitory effect is concentration-dependent and surmountable, consistent with competitive antagonism. The high selectivity over CRF1 is confirmed by the lack of significant inhibition of CRF1-mediated cAMP accumulation at concentrations up to 1 uM.
|
| Enzyme Assay |
The binding affinity of K41498 TFA to CRF2 receptors is determined using a cell-free radioligand displacement assay. Membranes from CHO cells expressing human CRF2alpha, CRF2beta, or CRF1 are prepared. Membranes are incubated with a fixed concentration of [125I]-sauvagine (0.1 nM) and varying concentrations (0.0001-10,000 nM) of K41498 TFA in binding buffer (50 mM HEPES, 5 mM MgCl2, 2 mM EGTA, 0.1% BSA, pH 7.4) for 60-90 minutes at room temperature. Bound and free radioligands are separated by rapid filtration through GF/C filters pre-soaked in 0.3% polyethyleneimine. Radioactivity is measured, and Ki values are calculated using a one-site competition model.
|
| Cell Assay |
For functional antagonist assays, CHO cells expressing human CRF2alpha are seeded in 96-well plates. Cells are pre-incubated with K41498 TFA (0.001-1000 nM) for 15 minutes, then stimulated with an EC80 concentration of sauvagine (e.g., 5 nM) for 15 minutes in the presence of 1 mM IBMX. The reaction is stopped by lysis, and intracellular cAMP levels are measured using a cAMP ELISA or a homogeneous TR-FRET cAMP kit. The IC50 for inhibition is calculated from dose-response curves. The percentage of inhibition is normalized to the maximal sauvagine response (100%) and basal levels (0%).
|
| Animal Protocol |
K41498 TFA can be evaluated in vivo in rodent models to study CRF2-mediated physiology. For example, in a cardiovascular study, rats are administered K41498 TFA via intracerebroventricular (ICV) injection (1-10 ug) or intravenously (0.1-1 mg/kg). Blood pressure and heart rate are continuously monitored. CRF2 antagonism prevents or reverses the hypotensive response to urocortin. In gastrointestinal studies, administration of K41498 TFA blocks CRF2-mediated delayed gastric emptying. The peptide can also be used in models of anxiety and stress where CRF2 plays a role.
|
| ADME/Pharmacokinetics |
K41498 TFA is a synthetic peptide with a molecular weight of approximately 2800-3000 Da (exact mass varies by vendor). The TFA salt enhances solubility and stability. As a peptide, K41498 TFA has a short plasma half-life (minutes) due to rapid proteolytic degradation, requiring frequent dosing or continuous infusion for sustained effects. It is soluble in water or PBS and can be stored at -20degC. For in vivo ICV administration, it is typically dissolved in artificial cerebrospinal fluid (ACSF) at concentrations of 1-10 ug/uL.
|
| Toxicity/Toxicokinetics |
K41498 TFA is generally well-tolerated at research doses in animals. No significant systemic toxicity has been reported. The TFA counterion is present in low amounts. Standard laboratory safety precautions (gloves, lab coat) should be followed when handling the peptide. The compound is for research use only and not for human therapeutic use. Inadvertent CRF2 antagonism could affect stress responses, gastrointestinal motility, and cardiovascular function, but these are on-target effects rather than toxicity.
|
| References |
|
| Additional Infomation |
K41498 TFA is a research peptide not approved for clinical use. It is an analogue of antisauvagine-30 (aSvg-30) and is considered one of the most selective CRF2 antagonists available. It is used to investigate the role of CRF2 in various physiological and pathological processes, including stress, anxiety, addiction, feeding behavior, cardiovascular regulation, and gastrointestinal function. The high selectivity for CRF2 over CRF1 makes it a superior tool compared to older less selective antagonists. The sequence is derived from a modified version of sauvagine, a CRF2-selective agonist from frog skin.
|
| Molecular Formula |
C164H277F3N48O48
|
|---|---|
| Molecular Weight |
3746.22
|
| Related CAS # |
K41498;434938-41-7
|
| Appearance |
White to off-white solid powder
|
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2669 mL | 1.3347 mL | 2.6694 mL | |
| 5 mM | 0.0534 mL | 0.2669 mL | 0.5339 mL | |
| 10 mM | 0.0267 mL | 0.1335 mL | 0.2669 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
