| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
| Targets |
KYA1797K targets the Wnt/β-catenin signaling pathway by directly binding to axin. Axin is a central scaffold protein in the β-catenin destruction complex, which also includes APC, GSK3β, and CK1α. By binding to the RGS domain of axin, KYA1797K enhances the interaction between axin and the destruction complex, promoting the activation of GSK3β. Activated GSK3β then phosphorylates β-catenin, marking it for ubiquitination and proteasomal degradation. This mechanism effectively inhibits the Wnt/β-catenin pathway and also leads to the degradation of Ras.
|
|---|---|
| ln Vitro |
By strengthening the β-catenin complex disruptor that activates GSK3β, KYA1797K directly attaches to the regulator of the G protein signaling domain of axin, starting the control of β-catenin and Ras. The growth of APC and KRAS CRC is successfully inhibited by KYA1797K. It also promotes the formation of the β-catenin destruction complex and activates GSK3β, which phosphorylates β-catenin and K-Ras at S33/S37/T41 and T144/T148. β-catenin and Ras are degraded by KYA1797K in SW480, LoVo, DLD1, and HCT15 cells in a dose-dependent manner. In DLD1 cells expressing WT β-catenin or WT K-Ras, KYA1797K destabilizes both Ras and β-catenin [1].
In vitro, KYA1797K is a potent inhibitor of Wnt/β-catenin signaling. It inhibits the expression of a reporter induced by Wnt3a-conditioned medium in HEK293 cells with an IC₅₀ of 0.75 μM. The compound inhibits the proliferation of CRC cells mainly through the destabilization of β-catenin with additional Ras degradation. This dual activity makes KYA1797K a particularly effective agent against cancers with mutations in both the Wnt/β-catenin and Ras pathways. |
| ln Vivo |
Both in the Apcmin/+/KrasG12DLA2 mouse model and in tagged APC and K-Ras mutant CRC cell xenograft mice, KYA1797K effectively decreases tumor size. Tumor weight and volume were 70% decreased by KYA1797K (25 mg/kg). Treatment causes a considerable decrease in Wnt/β-catenin and Ras signaling targets, as well as β-catenin and Ras protein levels [1].
In vivo, KYA1797K has demonstrated efficacy in suppressing the growth of colorectal cancers (CRCs) harboring APC and KRAS mutations. By binding to axin and enhancing the β-catenin destruction complex, it effectively inhibits tumor growth in vivo. These in vivo data confirm the potential of KYA1797K as a therapeutic agent for cancers driven by aberrant Wnt/β-catenin and Ras signaling. Further studies are needed to fully characterize its pharmacokinetic and pharmacodynamic profiles. |
| Enzyme Assay |
Non-cell-based assays for KYA1797K are not typical, as its mechanism involves the modulation of a multi-protein complex. However, its binding to axin can be studied using surface plasmon resonance (SPR) or biolayer interferometry (BLI) with purified axin protein. Its ability to enhance the activity of the β-catenin destruction complex can be assessed in cell-free systems using purified components.
|
| Cell Assay |
Cellular assays for KYA1797K are performed using HEK293 cells with a Wnt/β-catenin reporter system. Cells are treated with the compound at various concentrations, and reporter activity is measured. Its ability to inhibit Wnt3a-conditioned medium-induced reporter activation is quantified, and an IC₅₀ of 0.75 μM is determined. The compound's effects on β-catenin and Ras protein levels are assessed by Western blotting. CRC cell proliferation assays are used to confirm its anticancer activity.
|
| Animal Protocol |
In vivo animal models for KYA1797K include xenograft studies in immunodeficient mice bearing CRC cell lines with APC and KRAS mutations. The compound is administered via appropriate routes at various doses. Tumor growth inhibition is monitored over time. Pharmacodynamic markers such as β-catenin and Ras levels, as well as downstream target gene expression, are assessed in tumor tissues. These studies confirm the compound's in vivo efficacy and its mechanism of action.
|
| ADME/Pharmacokinetics |
KYA1797K has a molecular weight of 483.56 g/mol and a molecular formula of C₁₇H₁₃KN₂O₆S₂. Its CAS number is 1956356-56-1. The compound is supplied as a solid with a purity of >98%. It is soluble in DMSO. Storage conditions: -20°C. Detailed pharmacokinetic parameters such as half-life, bioavailability, and volume of distribution are not extensively reported in the available literature.
|
| Toxicity/Toxicokinetics |
Detailed toxicological data for KYA1797K are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is intended for research use only and is not for human consumption. Standard laboratory safety precautions should be followed when handling the compound.
|
| References | |
| Additional Infomation |
KYA1797K is a potent Wnt/β-catenin signaling inhibitor with an IC₅₀ of 0.75 μM. It binds directly to the RGS domain of axin, enhancing the β-catenin destruction complex and activating GSK3β. This leads to the degradation of both β-catenin and Ras. KYA1797K effectively suppresses the growth of CRCs harboring APC and KRAS mutations. Its CAS number is 1956356-56-1.
|
| Molecular Formula |
C17H11KN2O6S2
|
|---|---|
| Molecular Weight |
442.5013
|
| Exact Mass |
441.969
|
| CAS # |
1956356-56-1
|
| Related CAS # |
851304-36-4 (free acid);1956356-56-1;
|
| PubChem CID |
119057297
|
| Appearance |
Yellow to orange solid powder
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
28
|
| Complexity |
663
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=CC=C1C2=CC=C(O2)/C=C\3/C(=O)N(C(=S)S3)CCC(=O)[O-])[N+](=O)[O-].[K+]
|
| InChi Key |
(5Z)-5-[[5-(4-Nitrophenyl)-2-furanyl]methylene]-4-oxo-2-thioxo-3-thiazolidinepropanoic acid potassium salt
|
| InChi Code |
PHUNRLYHXGMOLG-WQRRWHLMSA-M
|
| Chemical Name |
KYA1797K
|
| 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) |
DMSO : ~6 mg/mL (~13.56 mM)
H2O : ~1 mg/mL (~2.26 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (2.26 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 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: 1 mg/mL (2.26 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2599 mL | 11.2994 mL | 22.5989 mL | |
| 5 mM | 0.4520 mL | 2.2599 mL | 4.5198 mL | |
| 10 mM | 0.2260 mL | 1.1299 mL | 2.2599 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
