| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Yaddle1 targets the mechanosensitive ion channel Piezo1, a trimeric, propeller-shaped channel that converts mechanical force into electrochemical signals. Piezo1 is involved in numerous physiological processes, including touch sensation, vascular development, and immune cell activation. Yaddle1 is a specific agonist of Piezo1, binding to the channel and inducing its opening in the absence of mechanical stimuli. This results in the influx of calcium ions (Ca2+), which triggers downstream signaling pathways, including T cell activation. The compound is a valuable tool for studying Piezo1 biology and as a potential vaccine adjuvant.
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| ln Vitro |
Yaddle1 is a potent, specific new-generation Piezo1 agonist with a half-maximal effective concentration (MEC50) of 0.4 microM. It exhibits significantly better kinetic solubility than Yoda1, the first-generation Piezo1 agonist. Yaddle1 triggers Ca2+ inflow in T cells and induces a T cell activation response, making it a valuable tool for studying Piezo1 in immune cells. The MEC50 for Ca2+ influx is 0.40 microM, which is comparable to or better than Yoda1. The compound‘s improved solubility (26.72 +/- 1.8 microM at pH 7.4) is approximately 10-fold higher than Yoda1 (1.22 +/- 0.11 microM at pH 7.4), making it more suitable for biological studies. Yaddle1 can be used for the study of vaccine adjuvants.
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| ln Vivo |
No specific in vivo activity data for Yaddle1 are reported in the search results. As a potent Piezo1 agonist, it has potential for evaluation in vivo as a vaccine adjuvant. In animal models, Piezo1 activation is known to induce T cell activation and enhance immune responses to co-administered antigens. Yaddle1 could be administered subcutaneously or intramuscularly with an antigen to test its adjuvant activity. No specific in vivo data are provided.
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| Enzyme Assay |
The binding of Yaddle1 to Piezo1 is measured by functional assays rather than direct binding assays because Piezo1 is a large, multimeric membrane protein. The primary assay is a Ca2+ influx assay using Piezo1-expressing cells. HEK293 cells stably expressing human Piezo1 are seeded in 96-well plates and loaded with a fluorescent calcium indicator (e.g., Fluo-4 AM). Yaddle1 is added at graded concentrations (0.01-100 microM), and the increase in fluorescence (λex=494 nm, λem=516 nm) is measured. The MEC50 (half-maximal effective concentration) of 0.40 microM is calculated. Patch-clamp electrophysiology can also be used to directly measure Piezo1 channel currents in Piezo1-expressing cells or in primary T cells. Yaddle1 is applied to the bath, and the inward current is measured. The solubility of Yaddle1 in PBS (pH 7.4) is measured by high-performance liquid chromatography (HPLC).
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| Cell Assay |
For cellular assays, primary human CD4+ T cells or Jurkat T cells are used. Cells are loaded with Fluo-4 AM and seeded in 96-well plates. Yaddle1 is added at graded concentrations (0.01-100 microM). The increase in intracellular Ca2+ is measured as described. The MEC50 for Ca2+ influx is 0.40 microM. T cell activation is measured by flow cytometry for CD69 and CD25 expression after 4-24 hours of treatment. Cytokine production (IL-2, IFN-gamma) is measured by ELISA. For antigen-specific T cell activation, T cells are co-cultured with antigen-presenting cells (APCs) and an antigen (e.g., OVA peptide) in the presence of Yaddle1. T cell proliferation is measured by CFSE dilution.
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| Animal Protocol |
No animal experiments for Yaddle1 are described in the search results. For in vivo evaluation of vaccine adjuvant activity, 6-8-week-old female C57BL/6 mice would be immunized subcutaneously (SC) with a model antigen (e.g., OVA) plus Yaddle1 (1-100 ug/mouse). Mice would be boosted after 14 days. At day 21, splenocytes would be harvested, and antigen-specific T cell responses (IFN-gamma ELISpot, T cell proliferation) and antibody titers (anti-OVA IgG) would be measured. No such data are provided.
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| ADME/Pharmacokinetics |
Yaddle1 (C14H₈ClF3N4OS, MW = 372.75, purity ≥98%, CAS 3041134-13-5) is a solid powder. For storage, the powder should be kept at -20degC for up to 3 years, sealed and protected from light. For in vitro use, stock solutions in DMSO (10-50 mM) can be prepared and stored at -80degC for up to 6 months or at -20degC for 1 month. The compound has a kinetic solubility of 26.72 +/- 1.8 microM in PBS (pH 7.4). For in vivo use, it can be formulated in 10% DMSO / 40% PEG300 / 5% Tween-80 / 45% saline. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for Yaddle1 are reported. As a research-grade Piezo1 agonist, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed. Piezo1 activation can have diverse effects, including on blood pressure and vascular tone, so caution should be exercised. No LD50 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
Yaddle1 is a research-grade, potent Piezo1 agonist. Piezo1 is a mechanically activated ion channel that was the subject of the 2021 Nobel Prize in Physiology or Medicine (shared by David Julius and Ardem Patapoutian for the discovery of temperature and touch receptors). Yaddle1 was developed to address the solubility and potency limitations of Yoda1, the first synthetic Piezo1 agonist. The name “Yaddle1” is a play on “Yoda1,” referencing the Star Wars character Yaddle, who is of the same species as Yoda. Yaddle1 has potential applications as a vaccine adjuvant, as Piezo1 activation in T cells enhances T cell receptor (TCR) signaling and promotes a more robust immune response. The compound has not entered clinical trials or received regulatory approval. It is for research use only.
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| Molecular Formula |
C14H8CLF3N4OS
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| Molecular Weight |
372.75
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| Appearance |
Solid powder
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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 | 2.6828 mL | 13.4138 mL | 26.8276 mL | |
| 5 mM | 0.5366 mL | 2.6828 mL | 5.3655 mL | |
| 10 mM | 0.2683 mL | 1.3414 mL | 2.6828 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.
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