PROTAC RIPK1 Degrader-1
Based on 1 Customer Validation
PROTAC RIPK1 Degrader-1 is a selective RIPK1 PROTAC degrader. PROTAC RIPK1 Degrader-1 induces complete degradation of RIPK1 through the ubiquitin-proteasome system by bridging the target protein RIPK1 and VHL E3 ubiquitin ligase. PROTAC RIPK1 Degrader-1 is applicable to melanoma-related research.
(Pink: RIPK1 ligand (HY-175371); Blue: VHL ligand (HY-112078); Black: linker (HY-175373)).
For research use only. We do not sell to patients.
- Purity : 99.66%
- Formula: C69H85N13O6S2
- Molecular Weight:1256.63
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Storage:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
Description
IC50 & Target
[1]|
RIPK1 |
VHL |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK-293T | DC50 |
<0.1 nM
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RIPK1 degradation in HEK293T-RIPK1-HiBiT cells assessed via bioluminescence signal reflecting RIPK1 protein level after 24 h incubation.
RIPK1 degradation in HEK293T-RIPK1-HiBiT cells assessed via bioluminescence signal reflecting RIPK1 protein level after 24 h incubation.
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40665578 |
| A-375 | DC50 |
41 nM
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RIPK1 degradation in human A375 melanoma cells assessed via Western blot analysis after 20 h incubation.
RIPK1 degradation in human A375 melanoma cells assessed via Western blot analysis after 20 h incubation.
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40665578 |
| B16-F10 | DC50 |
91 nM
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RIPK1 degradation in murine B16F10 melanoma cells assessed via Western blot analysis after 20 h incubation.
RIPK1 degradation in murine B16F10 melanoma cells assessed via Western blot analysis after 20 h incubation.
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40665578 |
In Vitro
PROTAC RIPK1 Degrader-1 (Compound 225-5) (0.003-3 μM; 1-20 h) rapidly and persistently induces RIPK1 degradation in a concentration- and time-dependent manner in human A375 cells and murine B16F10 melanoma cells, with DC50 values of 41 nM and 91 nM, respectively[1].
PROTAC RIPK1 Degrader-1 (0.1 μM; 24 h) specifically and significantly downregulates RIPK1 levels in the global proteome of A375 cells (with no significant changes in other off-target proteins)[1].
PROTAC RIPK1 Degrader-1 (20 h) effectively degrades RIPK1 in HEK293T-RIPK1-HiBiT cells, with a DC50 < 0.1 nM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human A375 melanoma cells, murine B16F10 melanoma cells
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Concentration:0.1 μM (A375 cells); 1.0 μM (B16F10 cells)
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Incubation Time:1, 2, 4, 8, 16, 20 h
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Result:Induced significant RIPK1 degradation as early as 1 h post-treatment, and sustained the degradation over the 20 h time course.
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Cell Line:human A375 melanoma cells, murine B16F10 melanoma cells
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Concentration:0.003, 0.006, 0.01, 0.03, 0.06, 0.1, 0.3, 0.6, 1, 3 μM
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Incubation Time:20 h
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Result:Induced dose-dependent RIPK1 degradation with a DC50 of 41 nM and Dₘₐₓ of 97% in A375 cells.
Induced dose-dependent RIPK1 degradation with a DC50 of 91 nM and Dₘₐₓ of 92% in B16F10 cells.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUClast | AUCinf | MRTINF_obs |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 5 mg/kg | i.p. | 5.41 h | 0.5 h | 3270 ng/mL | 4279 ng·h/mL | 4316 ng·h/mL | 2.03 h |
In Vivo
PROTAC RIPK1 Degrader-1 (20 mg/kg; i.p.; once daily; 11 days) reduces tumor volume by 89% compared to control and extends median survival from 36 to 51 days when combined with 6 Gy X-ray radiotherapy in humanized NSG mice bearing A375 melanoma[1].
PROTAC RIPK1 Degrader-1 (10-50 mg/kg; i.p., i.v.; once/twice daily; 3 days) achieves almost complete RIPK1 degradation in B16F10 and A375 melanoma tumors in mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (6 to 10 weeks old; B16F10 melanoma flank model)[1]
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Dosage:40 mg/kg (first 3 days); 20 mg/kg (subsequent 8 days)
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Administration:i.p.; once daily; 11 days total
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Result:Combined with radiation significantly delayed tumor growth and extended the median survival from 19 to 24 days compared to radiation alone.
Body weights remained stable across all treatment groups, indicating no observable toxicity.
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Animal Model:NSG (5 to 10 weeks old; humanized with 1×107 human peripheral blood mononuclear cells; A375 melanoma flank model)[1]
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Dosage:20 mg/kg
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Administration:i.p.; once daily; 11 days
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Result:Combined with radiation significantly reduced tumor volume (by 89% compared to the vehicle control, 85.4% compared to the product alone, and 70.2% compared to XRT alone).
Combined with radiation substantially extended the median survival from 36 to 51 days.
Body weights remained stable across all treatment groups, indicating the combination therapy did not induce apparent systemic toxicity.
Chemical Information
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Appearance Solid
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Molecular Weight 1256.63
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Formula C69H85N13O6S2
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Color White to off-white
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SMILES
O=C(N1CCC(CC1)CN2CCC(CN3CCN(CC(N[C@H](C(N4[C@H](C(N[C@@H](C)C5=CC=C(C6=C(C)N=CS6)C=C5)=O)C[C@@H](O)C4)=O)C(C)(C)C)=O)CC3)CC2)CN7C=C(C=N7)C8=CN=C(N)C9=C8SC=C9C%10=CC=C%11N(C(CC%12=CC=CC=C%12)=O)CCC%11=C%10
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (79.58 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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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 (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (1.99 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.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (283 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 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 (protect from light). 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 |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.7958 mL | 3.9789 mL | 7.9578 mL | 19.8945 mL |
| 5 mM | 0.1592 mL | 0.7958 mL | 1.5916 mL | 3.9789 mL | |
| 10 mM | 0.0796 mL | 0.3979 mL | 0.7958 mL | 1.9894 mL | |
| 15 mM | 0.0531 mL | 0.2653 mL | 0.5305 mL | 1.3263 mL | |
| 20 mM | 0.0398 mL | 0.1989 mL | 0.3979 mL | 0.9947 mL | |
| 25 mM | 0.0318 mL | 0.1592 mL | 0.3183 mL | 0.7958 mL | |
| 30 mM | 0.0265 mL | 0.1326 mL | 0.2653 mL | 0.6631 mL | |
| 40 mM | 0.0199 mL | 0.0995 mL | 0.1989 mL | 0.4974 mL | |
| 50 mM | 0.0159 mL | 0.0796 mL | 0.1592 mL | 0.3979 mL | |
| 60 mM | 0.0133 mL | 0.0663 mL | 0.1326 mL | 0.3316 mL |
PROTAC RIPK1 Degrader-1 Related Classifications
HY-175370 Related Classifications
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