Homo-PROTAC pVHL30 degrader 1
Based on 1 publication(s) in Google Scholar
Homo-PROTAC pVHL30 degrader 1 is a Homo-PROTAC autodegraders targeting the von Hippel-Lindau E3 ubiquitin ligase (VHL), with Kd values of 11 nM and 25 nM for pVHL19-EloBC and pVHL30-EloBC, respectively. Homo-PROTAC pVHL30 degrader 1 induces Cullin2 depletion, promotes VHL dimerization to form a ternary complex, and drives proteasome-dependent and CRL2-VHL-like ubiquitination-dependent autodegradation. Homo-PROTAC pVHL30 degrader 1 does not trigger hypoxic responses, and only causes extremely mild stabilization of hypoxia-inducible factor α subunits. Homo-PROTAC pVHL30 degrader 1 can be used in studies related to cervical cancer and osteosarcoma.
(Pink: VHL ligand (HY-125845); Blue: VHL ligand (HY-125845); Black: linker (HY-122702)).
For research use only. We do not sell to patients.
- Purity: 99.40%
- CAS No.: 2244684-49-7
- Formula: C58H82N8O14S2
- Molecular Weight:1179.45
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Storage:
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) Homo-PROTAC pVHL30 degrader 1
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Biological Activity
Description
IC50 & Target
[1]|
VHL |
pVHL19 11 nM (Kd) |
pVHL30 25 nM (Kd) |
In Vitro
Homo-PROTAC pVHL30 degrader 1 (CM11) (150 μM; 120 s intervals) tightly forms a 1:2 complex with purified pVHL19-Elongin B-Elongin C complex in vitro, with a measured KD of 11 nM, which represents an 18-fold higher binding affinity than that of VH032[1].
Homo-PROTAC pVHL30 degrader 1 (150 μM; 120 s intervals) tightly forms a 1:2 complex with the purified pVHL30-Elongin B-Elongin C complex in vitro, with a measured KD of 25 nM, which represents a 7.5-fold higher binding affinity than that of VH032[1].
Homo-PROTAC pVHL30 degrader 1 (30 μM; 20 min) induces the formation of a stable (pVHL19-Elongin B-Elongin C)2:CM11 ternary complex in vitro[1].
Homo-PROTAC pVHL30 degrader 1 (0.5-100 nM; 1 h) potently induces the formation of a ternary complex consisting of two VCB molecules in vitro via the AlphaLISA proximity assay[1].
Homo-PROTAC pVHL30 degrader 1 (1 nM-100 μM; 1-48 h) induces potent, time- and concentration-dependent, proteasome- and CRL2-VHL-dependent depletion of pVHL30 in HeLa cells, with a DC50 ranging from 10 to 100 nM[1].
Homo-PROTAC pVHL30 degrader 1 (1 nM-100 μM; 1-48 h) induces rapid, complete and sustained depletion of pVHL30 in U2OS cells[1].
Homo-PROTAC pVHL30 degrader 1 does not induce HIF-dependent hypoxic responses in HeLa-HRE or U2OS-HRE cells[1].
Homo-PROTAC pVHL30 degrader 1 does not induce upregulation of the HIF target gene CA9 in HeLa cells[1].
Homo-PROTAC pVHL30 degrader 1 (1 μM; 10 h) selectively induces depletion of pVHL30 and Cullin2 in HeLa cells, and unbiased proteomic analysis detects no significant off-target effects on other proteins[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HeLa cells
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Concentration:0.001, 0.01, 0.1, 1, 10 and 100 μM (4 h or 24 h); 1 μM (1-48 h); 1 μM (with pre-treatments: 3 μM MLN4924 (HY-70062), 50 μM MG132 (HY-13259), 150 μM VH032 (HY-120217))
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Incubation Time:1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 36 h, 48 h; 3 h (MLN4924 pre-treatment), 30 min (MG132/VH032 pre-treatment)
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Result:Induced concentration- and time-dependent depletion of pVHL30, with complete depletion observed at 10 nM after 4 h, and a half-degrading concentration (DC50) between 10 and 100 nM after 24 h.
Reduced pVHL30 levels by over 70% after 2 h of treatment with 1 μM, and essentially depleted pVHL30 after 8 h.
Abrogated pVHL30 degradation completely by pre-treatment with proteasome inhibitor MG132 or neddylation inhibitor MLN4924, and blocked degradation by pre-treatment with VHL inhibitor VH032.
Reduced cellular Cullin2 levels by up to 73% after 24 h treatment.
Caused only minimal stabilization of hydroxylated HIF-1α (Hdy-HIF-1α) and HIF-1α compared to hypoxia-inducing controls.
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Cell Line:U2OS cells
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Concentration:0.001, 0.01, 0.1, 1, 10 and 100 μM (10 h); 1 μM (1-48 h)
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Incubation Time:1 h, 2 h, 4 h, 8 h, 12 h, 24 h, 36 h, 48 h; 10 h
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Result:Induced complete depletion of pVHL30 within 1 h of treatment with 1 μM, and maintained effective depletion up to 48 h.
Showed a concentration-dependent activity profile matching observations in HeLa cells, with preferential degradation of pVHL30 over pVHL19.
Chemical Information
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CAS No. 2244684-49-7
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Appearance Solid
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Molecular Weight 1179.45
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Formula C58H82N8O14S2
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Color White to off-white
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SMILES
CC1=C(C2=CC=C(CNC([C@@H]3C[C@@]([H])(O)CN3C([C@H](C(C)(C)C)NC(COCCOCCOCCOCCOCCOCC(N[C@@H](C(C)(C)C)C(N4[C@H](C(NCC5=CC=C(C6=C(C)N=CS6)C=C5)=O)C[C@@]([H])(O)C4)=O)=O)=O)=O)=O)C=C2)SC=N1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Publications (1)
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Journal Impact Factor
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Most Recent
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Structure
PROTAC-mediated activation, rather than degradation, of a nuclear receptor reveals complex ligand-receptor interaction network. [Abstract]2024 Dec 5;32(12):2352-2363.e8. PMID: 39389062
Solvent & Solubility
In Vitro:
DMSO : ≥ 150 mg/mL (127.18 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : 25 mg/mL (21.20 mM; Need ultrasonic)
* "≥" means soluble, but saturation unknown.
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, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
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, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- 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: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.12 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (2.12 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Purity & Documentation
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Data Sheet (280 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
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, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O / DMSO | 1 mM | 0.8479 mL | 4.2393 mL | 8.4785 mL | 21.1963 mL |
| 5 mM | 0.1696 mL | 0.8479 mL | 1.6957 mL | 4.2393 mL | |
| 10 mM | 0.0848 mL | 0.4239 mL | 0.8479 mL | 2.1196 mL | |
| 15 mM | 0.0565 mL | 0.2826 mL | 0.5652 mL | 1.4131 mL | |
| 20 mM | 0.0424 mL | 0.2120 mL | 0.4239 mL | 1.0598 mL | |
| DMSO | 25 mM | 0.0339 mL | 0.1696 mL | 0.3391 mL | 0.8479 mL |
| 30 mM | 0.0283 mL | 0.1413 mL | 0.2826 mL | 0.7065 mL | |
| 40 mM | 0.0212 mL | 0.1060 mL | 0.2120 mL | 0.5299 mL | |
| 50 mM | 0.0170 mL | 0.0848 mL | 0.1696 mL | 0.4239 mL | |
| 60 mM | 0.0141 mL | 0.0707 mL | 0.1413 mL | 0.3533 mL | |
| 80 mM | 0.0106 mL | 0.0530 mL | 0.1060 mL | 0.2650 mL | |
| 100 mM | 0.0085 mL | 0.0424 mL | 0.0848 mL | 0.2120 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
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