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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
WSB1 Degrader 1 targets WSB1 (WD repeat and SOCS box-containing 1) protein. WSB1 is an E3 ubiquitin ligase component involved in protein ubiquitination and degradation. By degrading WSB1, the compound disrupts its function in cancer metastasis pathways, leading to anti-metastatic effects.
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| ln Vitro |
The treatment of H1299-WSB1 cells with WSB1 Degrader 1 (compound 4; 0.25-2500 nM; 2-24 hours) causes WSB1 degradation in a dose- and time-dependent manner[1]. In KHOS and H460 cell lines, WSB1 Degrader 1 (compound 4) demonstrates strong antimigration efficacy with IC50 values of 39.1 μM and 24.47 μM, respectively[1]. In KHOS cells, WSB1 Degrader 1 (compound 4) dramatically reduces the migration of cancer cells in both normoxia and hypoxia. When KHOS cells are exposed to hypoxia, WSB1 Degrader 1 (5 μM) treatment increases the levels of RhoGDI2 protein[1]. Applying WSB1 Degrader 1 to H1299-WSB1 cells significantly reduces their ability to heal wounds. The A2780-WSB1/KO cells are not able to have their wound-healing ability blocked by WSB1 Degrader 1; only the wild-type A2780 (A2780-WT) cells are[1].
In vitro, WSB1 Degrader 1 effectively induces degradation of WSB1 protein in cancer cell lines. This degradation leads to disruption of WSB1-mediated signaling pathways involved in cancer cell migration and invasion. The compound's potent activity and oral bioavailability make it a promising tool for studying WSB1 function and cancer metastasis. |
| ln Vivo |
Treatment with WSB1 Degrader 1 (compound 4; 100 mg/kg; po; daily; for 28 days) can successfully prevent cancer cells from metastasizing to the lungs[1]. WSB1 Degrader 1 (compound 4) was administered to rats orally at a dose of 100 mg/kg or intraperitoneally at a dose of 160 mg/kg. Both methods of administration were shown to have rapid absorption (Tmax) but rapid clearance (T1/2) for the oral dose. Additionally, appropriate blood exposure was demonstrated by the Cmax and AUC0-t values of WSB1 Degrader 1 in the oral or intraperitoneal dose groups[1].
In vivo, WSB1 Degrader 1 (100 mg/kg; oral; daily; for 28 days) effectively inhibits the pulmonary metastasis of cancer cells in rat models. This anti-metastatic effect demonstrates the compound's potential for therapeutic application in preventing cancer spread. The oral activity of the compound further supports its translational potential. |
| Enzyme Assay |
Cell-free assays for WSB1 Degrader 1 are not typically performed, as the compound acts by inducing protein degradation in cells. Its activity is assessed by measuring the binding affinity to WSB1 or by evaluating the compound's ability to promote WSB1 ubiquitination in reconstituted ubiquitination systems using purified E1, E2, and E3 enzymes.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: H1299-WSB1 cells Tested Concentrations: 0.25 nM, 2.5 nM, 25 nM, 250 nM, 2500 nM Incubation Duration: 2 hrs (hours), 4 hrs (hours), 6 hrs (hours), 8 hrs (hours), 12 hrs (hours), 24 hrs (hours) Experimental Results: Induced WSB1 degradation in time-dependent and dose-dependent manners. In vitro cellular assays involve treating cancer cell lines with WSB1 Degrader 1 at various concentrations and measuring WSB1 protein levels by Western blotting. Cell migration and invasion are assessed using Transwell or scratch assays. Cell viability and proliferation are measured using MTT or colony formation assays. |
| Animal Protocol |
Animal/Disease Models: Balb/c (nu/nu) mice bearing highly metastatic 4T1 breast cancer cells[1].
Doses: 100 mg/kg/day Route of Administration: po; daily ; for 28 days Experimental Results: Effectively inhibited the pulmonary metastasis of cancer cells. In vivo animal studies for WSB1 Degrader 1 are conducted using mouse or rat models of cancer metastasis. The compound is administered orally at doses such as 100 mg/kg daily for 28 days. Endpoints include assessment of metastatic tumor burden in the lungs or other organs, histopathological examination, and survival analysis. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of WSB1 Degrader 1 include oral activity, indicating good oral bioavailability. The compound's small molecular weight (334.41) facilitates tissue distribution. Detailed PK parameters such as half-life, Cmax, and AUC would need to be determined through dedicated studies.
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| Toxicity/Toxicokinetics |
Toxicological data for WSB1 Degrader 1 are limited. As a novel degrader, its toxicity profile has not been extensively reported. Standard toxicity assessments including acute, sub-chronic, and genotoxicity studies would be required for therapeutic development. The compound's oral activity suggests systemic exposure, necessitating thorough safety evaluation.
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| References | |
| Additional Infomation |
WSB1 Degrader 1 is a research compound with no clinical approvals. Its mechanism involves targeted degradation of WSB1 protein, leading to inhibition of cancer metastasis. The compound is a valuable tool for studying the role of WSB1 in cancer progression and for developing new anti-metastatic therapies. Its oral activity supports its potential for therapeutic development.
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| Molecular Formula |
C21H22N2O2
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|---|---|
| Molecular Weight |
334.4116
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| Exact Mass |
334.168
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| CAS # |
2306039-66-5
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| PubChem CID |
149706874
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
419
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C([H])([H])[H])C1C([H])=C([H])C(=C([H])C=1C([H])([H])[H])C1C([H])=C([H])C(N([H])[H])=NC=1C1C([H])=C([H])C(=C(C([H])([H])[H])C=1[H])OC([H])([H])[H]
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| InChi Key |
AUHCLHXXUVPUBD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H22N2O2/c1-13-11-15(5-8-18(13)24-3)17-7-10-20(22)23-21(17)16-6-9-19(25-4)14(2)12-16/h5-12H,1-4H3,(H2,22,23)
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| Chemical Name |
5,6-bis(4-methoxy-3-methylphenyl)pyridin-2-amine
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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) |
DMSO: 25 mg/mL (74.76 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% 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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9903 mL | 14.9517 mL | 29.9034 mL | |
| 5 mM | 0.5981 mL | 2.9903 mL | 5.9807 mL | |
| 10 mM | 0.2990 mL | 1.4952 mL | 2.9903 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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