| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg | |||
| 100mg | |||
| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
YW2065 targets the Wnt/β-catenin signaling pathway by stabilizing Axin-1. Axin-1 is a scaffolding protein that regulates proteasome degradation of β-catenin. By stabilizing Axin-1, YW2065 promotes the degradation of β-catenin, thereby inhibiting Wnt signaling. Simultaneously, YW2065 activates AMPK (AMP-activated protein kinase), a tumor suppressor and key regulator of cellular energy homeostasis.
|
|---|---|
| ln Vitro |
YW2065 is a potent inhibitor of the Wnt/β-catenin signaling pathway with an IC50 of 2.3 nM in Wnt-HEK293 luciferase gene reporter assays. It stabilizes Axin-1, promoting β-catenin degradation. The compound also activates AMPK. YW2065 exhibits excellent anti-colorectal cancer effects in vitro. Its dual activities of Wnt signaling inhibition and AMPK activation contribute to its anticancer efficacy.
|
| ln Vivo |
YW2065 has demonstrated favorable pharmacokinetic properties and suppressed tumor growth in a xenograft mouse model. It exhibits excellent anti-colorectal cancer effects in vivo. The anti-CRC effect of YW2065 was highlighted by its promising efficacy in a mice xenograft model. YW2065 showed favorable pharmacokinetic properties without obvious toxicity.
|
| Enzyme Assay |
Wnt/β-catenin signaling inhibition is measured using luciferase reporter assays in Wnt-HEK293 cells. Cells stably expressing a Wnt-responsive luciferase reporter are treated with YW2065 at varying concentrations in the presence of Wnt3a-conditioned medium. Luciferase activity is measured, and IC50 values are calculated from dose-response curves. Axin-1 stabilization and β-catenin degradation are confirmed by Western blot.
|
| Cell Assay |
Cellular activity of YW2065 is evaluated in colorectal cancer cell lines. Cells are treated with escalating concentrations of YW2065 for 48-72 hours. Cell viability is measured using CellTiter-Glo or MTT assays. Wnt signaling inhibition is confirmed by measuring β-catenin levels and expression of Wnt target genes (e.g., c-Myc, cyclin D1) by Western blot or qRT-PCR. AMPK activation is confirmed by measuring phospho-AMPK levels.
|
| Animal Protocol |
In vivo efficacy of YW2065 is evaluated in a xenograft mouse model of colorectal cancer. Tumor-bearing mice are administered YW2065 at 5 mg/kg prepared in 5% Kolliphor in saline. The compound is administered intravenously or via oral gavage. Tumor volume is measured bi-weekly, and tumor growth inhibition is calculated. Pharmacodynamic endpoints include assessment of Wnt signaling inhibition and AMPK activation in tumor tissues by immunohistochemistry or Western blot.
|
| ADME/Pharmacokinetics |
YW2065 demonstrates favorable pharmacokinetic properties. It has a molecular formula of C20H15BrN4O and a molecular weight of 407.26. The compound showed improved pharmacokinetic properties compared to the parent compound pyrvinium. It exhibits favorable PK properties and suppresses tumor growth in xenograft models. The compound is administered intravenously at 5 mg/kg or via oral gavage.
|
| Toxicity/Toxicokinetics |
YW2065 showed favorable pharmacokinetic properties without obvious toxicity. In preclinical studies, the compound was well-tolerated at efficacious doses. As a research compound, comprehensive toxicology profiling would be required for clinical development. The compound is for research use only and not for human therapeutic use.
|
| References |
1. Yang W, Li Y, Ai Y, Obianom ON, Guo D, Yang H, Sakamuru S, Xia M, Shu Y, Xue F. Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation. J Med Chem. 2019 Dec 10. doi: 10.1021/acs.jmedchem.9b01252. [Epub ahead of print] PubMed PMID: 31769984.
|
| Additional Infomation |
YW2065 was first reported in the Journal of Medicinal Chemistry (2019) by Yang W. et al. It is a pyrazole-4-carboxamide derivative. The compound exhibits anti-colorectal cancer effects through dual activities of Wnt/β-catenin signaling inhibition and AMPK activation. YW2065 achieves its inhibitory activity for Wnt signaling by stabilizing Axin-1. It is a promising therapeutic candidate for colorectal cancer.
|
| Molecular Formula |
C20H15BRN4O
|
|---|---|
| Molecular Weight |
407.263303041458
|
| Exact Mass |
406.04
|
| Elemental Analysis |
C, 58.98; H, 3.71; Br, 19.62; N, 13.76; O, 3.93
|
| CAS # |
2131223-85-1
|
| Related CAS # |
2131223-85-1;
|
| PubChem CID |
137375527
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
4.4
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
26
|
| Complexity |
504
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=C(C=NN1C2=CC=CC=C2Br)C(=O)NC3=NC4=CC=CC=C4C=C3
|
| InChi Key |
ATYUYECWVYSPBS-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H15BrN4O/c1-13-15(12-22-25(13)18-9-5-3-7-16(18)21)20(26)24-19-11-10-14-6-2-4-8-17(14)23-19/h2-12H,1H3,(H,23,24,26)
|
| Chemical Name |
1H-Pyrazole-4-carboxamide, 1-(2-bromophenyl)-5-methyl-N-2-quinolinyl-
|
| Synonyms |
YW2065; YW 2065; YW-2065;
|
| 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) |
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
|
|---|---|
| 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 | 2.4554 mL | 12.2772 mL | 24.5543 mL | |
| 5 mM | 0.4911 mL | 2.4554 mL | 4.9109 mL | |
| 10 mM | 0.2455 mL | 1.2277 mL | 2.4554 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
