WS3
Based on 1 Customer Validation
WS3 is an allosteric inhibitor of 14-3-3 (14-3-3ζ: Kd = 2.29 μM). WS3 activates GSK3β by disrupting the binding of 14-3-3-pGSK3β, promotes the ubiquitination and degradation of NRF2, and inhibits the NRF2-ARE signaling pathway (IC50 = 135 nM). It exerts antioxidant inhibition and chemotherapeutic/ferroptosis sensitizing effects in tumors with hyperactivated NRF2. WS3 binds to EBP1/IKKε and promotes the proliferation of β cells and retinal pigment epithelial (RPE) cells, which can be applied to islet regeneration and RPE expansion transplantation. WS3 is applicable to research related to age-related macular degeneration, retinal degeneration and non-small cell lung cancer.
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- Purity: 98.70%
- CAS No.: 1421227-52-2
- 화학식: C28H30F3N7O3
- 분자량:569.58
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
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14-3-3γ |
In Vitro
WS3 (25 nM; 3 days) induces proliferation in senescent passage six primary human fetal RPE cells, with 25 nM WS3 causing a four-fold increase in EdU-positive cells relative to DMSO control, and elicits similar responses in primary adult rat and adult human RPE cells[1].
WS3 (25 nM; serial passages through passage fifteen, split every three days) supports continuous proliferation of primary human fetal RPE cells through passage fifteen (maximal 1.95 doublings per passage at passage eleven), with proliferation ceasing immediately upon compound removal, and does not induce cell death during senescence[1].
WS3 (25 nM; from passage six to passage ten) does not induce chromosomal abnormalities or tumorigenic events during long-term culture of primary human fetal RPE cells from passage six to passage ten[1].
WS3 (25 nM) expanded primary human fetal RPE cells to passage ten differentiate into functional mature RPE monolayers (with cobblestone morphology, pigmentation, tight junctions, RPE marker expression, and POS phagocytosis) upon WS3 removal, and WS3-expanded primary adult human RPE cells similarly differentiate into mature RPE cells with appropriate gene expression[1].
WS3 induces dose-dependent proliferation of mouse R7T1 β cells with an EC50 of 0.074 μM[2].
WS3 (50-200 nM; 48 h) potently inhibits NRF2-ARE signaling in A549 cells with an IC50 of 135 nM, selectively reducing NRF2 and downstream target levels via proteasomal/ubiquitin-mediated degradation dependent on the SKP1-CUL1-β-TrCP complex, while sparing normal HUVEC and BEAS-2B cells[3].
WS3 (50-200 nM; 4-48 h) disrupts the 14-3-3ζ-pGSK3β interaction in A549 cells, activating GSK3β to promote CUL1-β-TrCP-mediated NRF2 ubiquitination and degradation, with this effect reversible via GSK3β or PP2A inhibition[3].
WS3 (20-400 nM; 24 h-2 week) induces oxidative stress, ferroptosis, and NRF2-dependent growth inhibition in A549 cells, with effects abrogated in NRF2-KO cells[3].
WS3 (20-200 nM; 48 h-2 week) synergizes with carboplatin and ferroptosis inducers to enhance growth inhibition of A549 cells[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A549 cells, HEK293T cells
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Concentration:50, 100 and 200 nM (48 h incubation, 4 h co-IP, 12 h pull-down); 200 nM (12-48 h incubation); 200 nM with 5-10 μM CHIR-99021 (HY-10182) pretreatment, 5 nM okadaic acid (HY-N6785) pretreatment
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Incubation Time:4 h (co-IP), 12 h (pull-down, inhibitor pretreatment), 12, 24, 36 and 48 h (200 nM), 24 h (inhibitor combination)
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Result:Reduced pGSK3β levels in a concentration- and time-dependent manner, accompanied by NRF2 downregulation, without affecting total GSK3β.
Disrupted the 14-3-3ζ-pGSK3β interaction via co-IP and pull-down assays.
Induced NRF2 degradation and ubiquitination that were reversed when 14-3-3ζ was overexpressed.
Induced NRF2 downregulation that was partially rescued via pretreatment with CHIR-99021 or okadaic acid.
Did not affect 14-3-3ζ interactions with canonical motif-containing partners (c-Raf, FOXO3A, P27).
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:dystrophic Royal College of Surgeons (RCS) (postnatal day 22; retinal degeneration model via MERTK gene inactivating mutation)[1]
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Dosage:25 nM
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Administration:culture media supplementation; seven passages
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Result:Achieved an average visual acuity of 0.49 cycles/degree at postnatal day 90.
Demonstrated luminance thresholds less than 1.7 log units over 35% of the superior colliculus area at postnatal day 90.
Preserved 4-6 layers of photoreceptors, compared to a single layer in control eyes.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1421227-52-2
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Appearance Solid
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분자량 569.58
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화학식 C28H30F3N7O3
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Color Light yellow to yellow
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SMILES
CN1CCN(CC1)CC2=C(C=C(C=C2)NC(NC3=CC=C(C=C3)OC4=CC(NC(C5CC5)=O)=NC=N4)=O)C(F)(F)F
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
용액&용해도
In Vitro:
DMSO : 2.2 mg/mL (3.86 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 3.33 mg/mL (5.85 mM); Suspended solution; Need ultrasonic
순도&문서
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Data Sheet (283 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1].
Swoboda JG, et al. Small molecule mediated proliferation of primary retinal pigment epithelial cells. ACS Chem Biol. 2013 Jul 19;8(7):1407-11.
[Content Brief]
[2].
Swoboda JG, et al. Small molecule mediated proliferation of primary retinal pigment epithelial cells. ACS Chem Biol. 2013 Jul 19;8(7):1407-11.
[Content Brief]
[3].
Zhao J, et al. Discovery of an allosteric 14-3-3 inhibitor for suppressing NRF2-driven cancer via phenotypic screening and chemoproteomic-based target deconvolution. Chem Sci. 2025 Aug 20;16(37):17248-17260.
[Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.7557 mL | 8.7784 mL | 17.5568 mL | 43.8920 mL |
WS3 Related Classifications
HY-12462 Related Classifications
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