| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
αvβ5 8.2 (pIC50)
alphavbeta5 integrin-IN-1 specifically targets the alphavbeta5 integrin heterodimer. It binds with high affinity to the extracellular ligand-binding pocket of the integrin, competitively blocking the binding of its natural ligands, particularly vitronectin. By antagonizing alphavbeta5, this compound disrupts alphavbeta5-mediated cell adhesion and migration and inhibits downstream signaling pathways, such as the FAK/PI3K/Akt axis, thereby affecting cell survival and proliferation. |
|---|---|
| ln Vitro |
In vitro, alphavbeta5 integrin-IN-1 potently inhibits cell adhesion to vitronectin-coated surfaces, typically with an IC50 in the low nanomolar range. It can effectively block alphavbeta5-mediated cell migration and invasion in various cancer cell lines. The selectivity of the inhibitor for alphavbeta5 over other closely related integrins (e.g., alphavbeta3, alpha5beta1) can be assessed in cell-free binding assays to confirm its specificity as a research tool.
|
| ln Vivo |
In vivo, alphavbeta5 integrin-IN-1 has shown efficacy in preclinical models of neovascular age-related macular degeneration (wet AMD), where alphavbeta5 integrin plays a significant role in pathological angiogenesis. By inhibiting alphavbeta5, the compound reduces blood vessel growth in the eye. It is also being explored in cancer models to evaluate its potential to inhibit tumor growth and metastasis by targeting the tumor vasculature and the tumor microenvironment.
|
| Enzyme Assay |
For a cell-free system, a solid-phase binding assay is used to determine the inhibitory activity. Purified recombinant alphavbeta5 integrin is immobilized on a microplate. A biotinylated vitronectin ligand is added to the plate along with varying concentrations of alphavbeta5 integrin-IN-1. After washing, the amount of bound ligand is measured using HRP-conjugated streptavidin and a colorimetric substrate. The concentration of compound that inhibits 50% of the binding (IC50) is calculated.
|
| Cell Assay |
In cellular assays, cells expressing alphavbeta5 integrin (e.g., HUVEC endothelial cells or specific cancer cell lines) are seeded in 96-well plates pre-coated with vitronectin. The cells are pre-incubated with serial dilutions of alphavbeta5 integrin-IN-1 (e.g., from 1 pM to 10 uM) for 30 minutes. After allowing the cells to attach for 1-2 hours, non-adherent cells are washed away, and the number of adherent cells is quantified using a cell viability dye (e.g., Calcein-AM) or a crystal violet stain. Cell migration is assessed by a Boyden chamber assay with the compound added to the media.
|
| Animal Protocol |
For in vivo studies in a mouse model of CNV (choroidal neovascularization) for wet AMD, laser photocoagulation is used to rupture Bruch's membrane in the eyes of mice. alphavbeta5 integrin-IN-1 is formulated as a solution (e.g., in 5% DMSO and 95% saline). The compound is administered intravitreally or systemically via intraperitoneal (IP) injection. After 1-2 weeks, the mice are perfused with a fluorescein isothiocyanate (FITC)-labeled lectin, and the area of CNV in the flat-mounted choroids is measured by confocal microscopy.
|
| ADME/Pharmacokinetics |
Specific ADME data for alphavbeta5 integrin-IN-1 is not provided in the standard literature. As a small-molecule antagonist, its bioavailability and half-life are critical for systemic efficacy. For ocular applications, local administration (intravitreal injection) is a common route to achieve high intraocular concentrations while minimizing systemic exposure. Its formulation requires solubility in a vehicle compatible with ocular tissues.
|
| Toxicity/Toxicokinetics |
No specific toxicology data for alphavbeta5 integrin-IN-1 is presented. Integrins are important for maintaining normal tissue architecture, and systemic inhibition of alphavbeta5 could potentially lead to off-target effects. Preclinical toxicology studies are required to assess safety, but such data is not typical for a research-grade compound of this type. It is not for human use.
|
| References | |
| Additional Infomation |
alphavbeta5 integrin is often co-expressed with its close homolog, alphavbeta3, but they have distinct and sometimes opposing roles in angiogenesis. alphavbeta5 integrin has been implicated in VEGF-mediated angiogenesis in the eye, making it a target for AMD. This compound serves as a selective chemical probe to differentiate the specific contributions of alphavbeta5 from those of other integrins in complex biological processes. It is a preclinical research tool.
|
| Molecular Formula |
C25H28F3N3O3
|
|---|---|
| Molecular Weight |
475.50
|
| Exact Mass |
475.208
|
| CAS # |
2615912-33-7
|
| PubChem CID |
162641728
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.1
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
34
|
| Complexity |
719
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
[C@@H](C1C=CC=C(C(F)(F)F)C=1)(CC(=O)O)C(N1CC[C@@H](CCC2=CC=C3CCCN=C3N2)C1)=O
|
| InChi Key |
NUPIGKKRXBENIY-IERDGZPVSA-N
|
| InChi Code |
InChI=1S/C25H28F3N3O3/c26-25(27,28)19-5-1-3-18(13-19)21(14-22(32)33)24(34)31-12-10-16(15-31)6-8-20-9-7-17-4-2-11-29-23(17)30-20/h1,3,5,7,9,13,16,21H,2,4,6,8,10-12,14-15H2,(H,29,30)(H,32,33)/t16-,21+/m1/s1
|
| Chemical Name |
(3S)-4-oxo-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]-3-[3-(trifluoromethyl)phenyl]butanoic acid
|
| 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 (210.30 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (5.26 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1030 mL | 10.5152 mL | 21.0305 mL | |
| 5 mM | 0.4206 mL | 2.1030 mL | 4.2061 mL | |
| 10 mM | 0.2103 mL | 1.0515 mL | 2.1030 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
