| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
| Targets |
KY1220 targets the Wnt/β-catenin signaling pathway, a critical regulator of cell proliferation, differentiation, and stem cell renewal. By inhibiting this pathway, KY1220 promotes the degradation of β-catenin, a key transcriptional co-activator in the pathway, and simultaneously destabilizes Ras, a small GTPase that is frequently mutated in cancer. This dual-targeting mechanism is unique and makes KY1220 a promising candidate for cancer research, particularly for treating malignancies driven by aberrant Wnt/β-catenin and Ras pathway activation.
|
|---|---|
| ln Vitro |
In HEK293 reporter cells, KY1220's IC50 is 2.1 μM. In HEK293 cells, KY1220 dose-dependently decreases the activation of TOPflash reporter gene triggered by Wnt3a-CM as well as the mRNA expression of Wnt target genes MYC and CCND1. Following KY1220 treatment, β-catenin and panRas protein levels in HEK293 cells were also decreased in a dose-dependent manner, while the mRNA levels of CTNNB1 (which encodes β-catenin), NRAS, KRAS, and HRAS did not change. The progression of CRC is significantly influenced by K-Ras, which is also destabilized by KY1220 through polyubiquitin-dependent proteasomal degradation. The breakdown rate of Ras and β-catenin in the SW480 cell line is accelerated by KY1220. In SW480 cells containing KRAS mutations, Ras instability induced by KY1220 suppresses the actions of ERK and Akt, which are downstream effectors of Ras. The growth and transformation of HCT15, SW480, D-WT, and D-MT CRC cells were successfully suppressed following KY1220 treatment [1].
In vitro, KY1220 demonstrates potent activity by destabilizing both β-catenin and Ras. In HEK293 reporter cells, it inhibits Wnt/β-catenin pathway activity with an IC₅₀ of 2.1 μM. The compound dose-dependently decreases Wnt3a-CM-induced TOPflash reporter activation and reduces the mRNA expression of Wnt target genes CCND1 and MYC in HEK293 cells. These in vitro activities confirm its mechanism as a dual destabilizer of β-catenin and Ras and its potential as an anticancer agent. |
| ln Vivo |
Detailed in vivo activity data for KY1220 are not extensively reported in the available literature. However, as a compound that promotes the degradation of β-catenin and Ras and disrupts oncogenic signaling, it is expected to have in vivo efficacy in tumor models. Its ability to target both the Wnt/β-catenin and Ras pathways, which are frequently co-activated in cancers, suggests significant potential for antitumor activity in vivo. Further in vivo studies, such as xenograft models, would be required to fully characterize its therapeutic potential.
|
| Enzyme Assay |
Non-cell-based assays for KY1220 are not typical, as its mechanism involves the destabilization of proteins through pathway modulation. However, its activity can be assessed using reporter gene assays in cell-based systems. The compound's ability to inhibit the Wnt/β-catenin pathway can be measured using TOPflash reporter assays in cell lysates.
|
| Cell Assay |
Cellular assays for KY1220 are performed using HEK293 cells stably transfected with a TOPflash reporter. Cells are treated with the compound at various concentrations, and reporter activity is measured. The compound's ability to inhibit Wnt3a-conditioned medium-induced reporter activation is quantified, and an IC₅₀ of 2.1 μM is determined. The expression of Wnt target genes such as CCND1 and MYC is measured by qPCR to confirm pathway inhibition.
|
| Animal Protocol |
In vivo animal models for KY1220 would be required to assess its therapeutic potential. Based on its mechanism as a dual destabilizer of β-catenin and Ras, relevant models could include xenograft studies in immunodeficient mice bearing colorectal cancer or other solid tumor cell lines. The compound would be administered via appropriate routes at various doses. Tumor growth inhibition would be monitored over time. Pharmacodynamic markers such as β-catenin and Ras levels in tumor tissues would be assessed.
|
| ADME/Pharmacokinetics |
KY1220 has a molecular weight of 338.36 g/mol and a molecular formula of C₁₈H₁₄N₂O₄S. Its CAS number is 292168-79-7. 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 KY1220 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 |
5-[[1-(4-nitrophenyl)-2-pyrrolidinyl]methylene]-2-thiomethylene-4-imidazolone is a member of the pyrrole class of compounds.
KY1220 is a small molecule that destabilizes both β-catenin and Ras by targeting the Wnt/β-catenin pathway. It has an IC₅₀ of 2.1 μM in HEK293 reporter cells. The compound dose-dependently decreases Wnt3a-CM-induced TOPflash reporter activation and mRNA expression of Wnt target genes CCND1 and MYC. KY1220 is a promising candidate for cancer research, particularly for treating malignancies driven by aberrant Wnt/β-catenin and Ras pathway activation. Its CAS number is 292168-79-7. |
| Molecular Formula |
C14H10N4O3S
|
|---|---|
| Molecular Weight |
314.319200992584
|
| Exact Mass |
314.047
|
| CAS # |
292168-79-7
|
| Related CAS # |
292168-79-7;
|
| PubChem CID |
6011878
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
1.9
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
22
|
| Complexity |
523
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S=C1NC(/C(=C/C2=CC=CN2C2C=CC(=CC=2)[N+](=O)[O-])/N1)=O
|
| InChi Key |
FMLUAKSJMUPACD-WQLSENKSSA-N
|
| InChi Code |
InChI=1S/C14H10N4O3S/c19-13-12(15-14(22)16-13)8-11-2-1-7-17(11)9-3-5-10(6-4-9)18(20)21/h1-8H,(H2,15,16,19,22)/b12-8-
|
| Chemical Name |
(Z)-5-((1-(4-Nitrophenyl)-1H-pyrrol-2-yl)methylene)-2-thioxoimidazolidin-4-one
|
| Synonyms |
KY1220 KY-1220 KY 1220
|
| 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 : ~50 mg/mL (~159.07 mM)
|
|---|---|
| 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 | 3.1815 mL | 15.9074 mL | 31.8147 mL | |
| 5 mM | 0.6363 mL | 3.1815 mL | 6.3629 mL | |
| 10 mM | 0.3181 mL | 1.5907 mL | 3.1815 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
