| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| Other Sizes |
| Targets |
IPAG targets the sigma-1 receptor (σ1R), a unique chaperone protein located at the endoplasmic reticulum (ER) and plasma membrane, which is involved in modulating ion channels, cell survival, and stress responses. It acts as a potent sigma-1 receptor antagonist with a pKi of 4.3. By blocking sigma-1 receptor signaling, IPAG engages the unfolded protein response (UPR) and induces autophagy in cancer cells. The compound has also been noted as a potent NMDA receptor antagonist at σ sites, though its primary research application is as a sigma-1 receptor tool.
|
|---|---|
| ln Vitro |
When IPAG inhibits Sigma1, PD-L1 in PC3 (hormone-insensitive prostate cancer) and MDA-MB-231 (triple-negative breast cancer) cell lines is autolysosomally degraded, and the amount of functional PD-L1 on the cell surface cells is decreased [2]. 100±8 μg per 106 cells were generated on average after IPAG treatment. IPAG has the ability to stop cell division. Cell mass is decreased by IPAG therapy [3]. The phosphorylation of the translation regulatory proteins p70S6K, S6, and 4E-BP1 is inhibited by IPAG administration [3].
In vitro, IPAG inhibits sigma-1 receptor activity and induces autophagic degradation of PD-L1 in PC3 (hormone-insensitive prostate cancer) and MDA-MB-231 (triple-negative breast cancer) cell lines. Treatment with IPAG decreases the amount of functional PD-L1 on the cell surface and reduces cell mass. IPAG also inhibits the phosphorylation of translation regulatory proteins p70S6K, S6, and 4E-BP1. It has the ability to stop cell division and induce apoptosis. In cell viability assays using T47D cells at 10 μM for 24 hours, IPAG treatment resulted in a reduction in cell size. |
| ln Vivo |
In vivo, IPAG has been used in preclinical studies to evaluate sigma-2 signaling in tumor progression and neurodegeneration. While specific in vivo efficacy data for IPAG is limited in the provided literature, its role as a sigma-1 receptor antagonist suggests potential for studying conditions involving sigma receptor modulation, such as cancer, depression, and neurodegenerative diseases. The compound's ability to induce autophagy and degrade PD-L1 in cancer cells supports its utility in immuno-oncology research.
|
| Enzyme Assay |
The binding affinity of IPAG for the sigma-1 receptor is assessed using radioligand binding assays. Membranes from cells expressing the sigma-1 receptor are incubated with a radiolabeled ligand (e.g., [³H]-(+)-pentazocine) and varying concentrations of IPAG. After incubation, bound and free radioligand are separated by filtration, and the radioactivity is measured. The inhibition constant (Ki) or pKi is calculated from competition curves. This assay confirms the compound's affinity for the sigma-1 receptor and its selectivity over other receptors.
|
| Cell Assay |
Cell Viability Assay[3]
Cell Types: T47D Cell Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: The average forward scatter height (FSC-H) of DMSO (control) measured 412±5, while the average FSC-H of IPAG The treated cells were 412±5 and 390±4. Western Blot Analysis [3] Cell Types: T47D Cell Tested Concentrations: 10 μM Incubation Duration: Experimental Results: diminished levels of phosphothreonine 389-p70S6 kinase (P-S6K), phosphoserine 235/236-ribosomal S6 (P-S6) , and phosphoserine 65-4E-BP1 (P-4E-BP1). The cellular activity of IPAG is evaluated in various cancer cell lines, such as PC3 and MDA-MB-231 cells. Cells are treated with IPAG at concentrations such as 10 μM for 24 hours. The compound's effect on cell viability is assessed using assays like MTT or by measuring cell size via forward scatter height (FSC-H) in flow cytometry. Its ability to induce autophagy and degrade PD-L1 is confirmed by Western blot analysis of LC3-II (autophagy marker) and PD-L1 levels. The inhibition of signaling pathways is assessed by Western blot for phosphorylated p70S6K, S6, and 4E-BP1. |
| Animal Protocol |
In animal studies, IPAG is typically administered to rodents via intraperitoneal (i.p.) or oral administration. Dosing regimens would be determined based on the specific disease model and the compound's pharmacokinetic properties. In tumor models, the compound's effect on tumor growth, immune cell infiltration, and biomarkers such as PD-L1 expression would be assessed. Its utility in evaluating sigma-2 signaling in tumor progression and neurodegeneration makes it a valuable tool for in vivo pharmacology studies.
|
| ADME/Pharmacokinetics |
IPAG has a molecular weight of 395.28 g/mol and a chemical formula of C17H22IN3. It is a white to off-white solid powder with a LogP of 4.615. The compound is soluble in DMSO and is typically stored at room temperature. It has a purity of ≥98% (HPLC). Detailed pharmacokinetic parameters such as half-life and bioavailability are not extensively documented in the provided sources, but its use in preclinical studies suggests it has suitable properties for in vivo research.
|
| Toxicity/Toxicokinetics |
Formal toxicology data for IPAG is not extensively documented in the provided sources, as it is a research compound not intended for human therapeutic use. Its safety profile has not been established in comprehensive toxicology studies. However, its use in cell-based assays at concentrations up to 10 μM suggests it is tolerated in those contexts. As with all research chemicals, standard laboratory safety precautions should be followed when handling this compound.
|
| References |
|
| Additional Infomation |
IPAG is a potent sigma receptor antagonist.
IPAG (CAS: 193527-91-2) is a valuable and widely used chemical probe for studying sigma-1 receptor biology. Its selectivity for the sigma-1 receptor and its ability to induce autophagy and PD-L1 degradation make it a key tool for investigating the role of sigma receptors in cancer, neurobiology, and cell death. The compound has been cited in scientific literature for its potential in treating cancer and depression. It is available from various commercial suppliers for research purposes and continues to be used in preclinical studies to evaluate sigma receptor signaling in disease models. |
| Molecular Formula |
C17H22IN3
|
|---|---|
| Molecular Weight |
395.28115606308
|
| Exact Mass |
395.086
|
| CAS # |
193527-91-2
|
| PubChem CID |
4239764
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.615
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
1
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
21
|
| Complexity |
386
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
UUKPIWYXWLJPJF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H22IN3/c18-14-1-3-15(4-2-14)20-17(19)21-16-12-6-10-5-11(8-12)9-13(16)7-10/h1-4,10-13,16H,5-9H2,(H3,19,20,21)
|
| Chemical Name |
2-(2-adamantyl)-1-(4-iodophenyl)guanidine
|
| 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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~8.33 mg/mL (~21.07 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.83 mg/mL (2.10 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), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 8.3 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 0.83 mg/mL (2.10 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 8.3 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: ≥ 0.83 mg/mL (2.10 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 | 2.5299 mL | 12.6493 mL | 25.2985 mL | |
| 5 mM | 0.5060 mL | 2.5299 mL | 5.0597 mL | |
| 10 mM | 0.2530 mL | 1.2649 mL | 2.5299 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
