PROTAC BTK Degrader-6
Based on 1 Customer Validation
PROTAC BTK Degrader-6 is an orally active PROTAC-based BTK degrader with a DC50 of 3.18 nM. PROTAC BTK Degrader-6 induces BTK degradation via proteasomal degradation, ubiquitination, and CRBN ligase recruitment pathways. PROTAC BTK Degrader-6 inhibits NF-κB activation, mRNA expression of IL-1β and IL-6, as well as the secretion of pro-inflammatory cytokines. PROTAC BTK Degrader-6 reduces inflammatory responses in a zymosan-induced mouse model of peritonitis. PROTAC BTK Degrader-6 can be used in peritonitis-related research.
(Pink: Btk ligand (HY-150885); Blue: Cereblon ligand (HY-45808); Black: linker).
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 99.24%
- CAS No.: 2767204-39-5
- Formule: C45H47N11O6
- Masse moléculaire:837.92
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
NF-κB |
IL-1β |
IL-6 |
In Vitro
PROTAC BTK Degrader-6 (compound 15) (0.15-10000 nM; 4-72 h) potently degrades BTK in Ramos cells, with a DC50 of 3.18 nM and a maximum degradation rate of 99.90%. The degradation effect persists for at least 48 h after washout, and the agent functions through a proteasome-dependent pathway that relies on the binding of BTK and CRBN[1].
PROTAC BTK Degrader-6 (0.1-1000 nM; 24 h) potently degrades BTK in Mino cells, with a DC50 of 7.07 nM and a maximum degradation rate of 99.99%[1].
PROTAC BTK Degrader-6 (2.5-20 μM; 24 h) does not reduce the viability of RAW264.7 cells after 24 h of treatment at concentrations up to 10 μM[1].
PROTAC BTK Degrader-6 (0.1-10 μM; 1 h pre-treatment, followed by 24 h co-incubation with LPS) dose-dependently degrades BTK and inhibits NF-κB activation in LPS-stimulated RAW264.7 cells by reducing the phosphorylation levels of BTK and p65, as well as the phosphorylation and degradation of IκB-α[1].
PROTAC BTK Degrader-6 (0.1-10 μM; 2 h pre-treatment followed by 3 h LPS stimulation for RT-qPCR; co-incubation with LPS for ELISA) dose-dependently inhibits the mRNA expression and protein secretion of pro-inflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW264.7 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human B-lymphocytic Ramos cells
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Concentration:0.15, 0.5, 1.5, 15, 40, 120, 370, 1000, 3000, 10000 nM
100 nM (wash out) -
Incubation Time:24 h
4 h, 8 h, 12 h, 24 h
24 h followed by washout and incubation for 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h -
Result:Reduce BTK levels by 99.42% at 100 nM for 24 h.
Induce concentration-dependent BTK degradation with a DC50 of 3.18 nM and a maximal degradation rate (Dmax) of 99.90%; a hook effect was observed at concentrations ≥10000 nM.
Maintain BTK degradation for at least 48 h after washout following 24 h treatment with 100 nM.
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Cell Line:human B-lymphocytic Ramos cells
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Concentration:100 nM (pre-treatment with 200 nM Ibrutinib (HY-10997), 200 nM pomalidomide (HY-10984), 200 nM MG132 (HY-13259), or 200 nM Bafilomycin)
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Incubation Time:8 h (after 2 h pre-treatment)
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Result:Achieve near-complete BTK depletion after 8 h of treatment with 100 nM.
Have its BTK degradation blocked by pre-treatment with Ibrutinib, pomalidomide, or MG132, while Bafilomycin has no effect on its BTK degradation activity.
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Cell Line:human lymphoblastic Mino cells
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Concentration:0.15, 0.5, 1.5, 5, 15, 40, 120, 370, 1000, 3000, 10000 nM
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Incubation Time:24 h
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Result:Induce concentration-dependent BTK degradation with a DC50 of 7.07 nM and a maximal degradation rate (Dmax) of 99.99%; no hook effect was observed at concentrations up to 10000 nM.
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Cell Line:mouse macrophagic RAW264.7 cells
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Concentration:2.5, 5, 10, 20 μM
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Incubation Time:24 h
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Result:Exert little effect on the viability of RAW264.7 cells at concentrations up to 10 μM.
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Cell Line:LPS-stimulated mouse macrophagic RAW264.7 cells
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Concentration:0.1 μM, 1 μM, 10 μM
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Incubation Time:1 h pre-treatment, followed by 24 h co-incubation with LPS
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Result:Degrade BTK protein significantly and dose-dependently in LPS-stimulated RAW264.7 cells.
Reduce levels of p-BTK and p-p65, prevent the degradation of IκB-α, and inhibit IκB-α phosphorylation.
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Cell Line:LPS-stimulated mouse macrophagic RAW264.7 cells
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Concentration:0.1 μM, 1 μM, 10 μM
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Incubation Time:2 h pre-treatment followed by 3 h LPS stimulation
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Result:Inhibited the mRNA expression and protein secretion of proinflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW264.7 cells.
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Cell Line:LPS-stimulated mouse macrophagic RAW264.7 cells
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Concentration:0.1 μM, 1 μM, 10 μM
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Incubation Time:3 h co-incubation with LPS
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Result:Inhibited the mRNA expression and protein secretion of proinflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW264.7 cells.
Parmacokinetics
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 10-12 weeks old)[1]
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Dosage:10 mg/kg; 20 mg/kg; 50 mg/kg
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Administration:i.p.; single pretreatment 1 hour prior to zymosan challenge
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Result:Dose-dependently reduced myeloid cell recruitment to the peritoneal cavity.
Exhibited better anti-inflammatory efficacy than 10 mg/kg ibrutinib at 10 mg/kg.
Dose-dependently decreased IL-1β and IL-6 levels in peritoneal lavage fluid.
Chemical Information
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CAS No. 2767204-39-5
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Appearance Solid
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Masse moléculaire 837.92
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Formule C45H47N11O6
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Color Light yellow to yellow
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SMILES
O=C(CN1CCN(CC2CN(C3=CC(C(N(C4C(NC(CC4)=O)=O)C5=O)=O)=C5C=C3)C2)CC1)N(CC6)CCC6N7C8=C(C(N)=NC=N8)C(C(C=C9)=CC=C9OC%10=CC=CC=C%10)=N7
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (119.34 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. 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. 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 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.98 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 (2.98 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.
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.
Pureté et documentation
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Fiche technique (282 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Instruction de manipulation (2659 KB)
Références
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. 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 | 1.1934 mL | 5.9672 mL | 11.9343 mL | 29.8358 mL |
| 5 mM | 0.2387 mL | 1.1934 mL | 2.3869 mL | 5.9672 mL | |
| 10 mM | 0.1193 mL | 0.5967 mL | 1.1934 mL | 2.9836 mL | |
| 15 mM | 0.0796 mL | 0.3978 mL | 0.7956 mL | 1.9891 mL | |
| 20 mM | 0.0597 mL | 0.2984 mL | 0.5967 mL | 1.4918 mL | |
| 25 mM | 0.0477 mL | 0.2387 mL | 0.4774 mL | 1.1934 mL | |
| 30 mM | 0.0398 mL | 0.1989 mL | 0.3978 mL | 0.9945 mL | |
| 40 mM | 0.0298 mL | 0.1492 mL | 0.2984 mL | 0.7459 mL | |
| 50 mM | 0.0239 mL | 0.1193 mL | 0.2387 mL | 0.5967 mL | |
| 60 mM | 0.0199 mL | 0.0995 mL | 0.1989 mL | 0.4973 mL | |
| 80 mM | 0.0149 mL | 0.0746 mL | 0.1492 mL | 0.3729 mL | |
| 100 mM | 0.0119 mL | 0.0597 mL | 0.1193 mL | 0.2984 mL |
PROTAC BTK Degrader-6 Related Classifications
HY-149391 Related Classifications
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