Art. -Nr.: HY-149391

PROTAC BTK Degrader-6

Name: PROTAC BTK Degrader-6
Brand: MedChemExpress
SKU: HY-149391
Price: 540.00 USD
Availability: InStock
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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).

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Reinheit : 99.24%
CAS. Nr.: 2767204-39-5
Formel: C₄₅H₄₇N₁₁O₆
Molecular Weight:837.92

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

PROTAC BTK Degrader-6 Chemical Structure

CAS. Nr.: 2767204-39-5

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

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^[1]. (Pink: Btk ligand (HY-150885); Blue: Cereblon ligand (HY-45808); Black: linker).

IC₅₀ & Target

^[1]

NF-κB

IL-1β

IL-6

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Alle NF-κB Isoform-spezifische Produkte anzeigen :

Alle Interleukin Related Isoform-spezifische Produkte anzeigen :

In Vitro

OthersInnate ImmunityCytokines & Chemokines

Others

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].

Innate Immunity

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].

Cytokines & Chemokines

Innate Immunity

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.

Western Blot Analysis^[1]

Cell Line:

human B-lymphocytic Ramos cells
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.

Western Blot Analysis^[1]

Cell Line:

human B-lymphocytic Ramos cells
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)
Incubation Time:

8 h (after 2 h pre-treatment)
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.

Western Blot Analysis^[1]

Cell Line:

human lymphoblastic Mino cells
Concentration:

0.15, 0.5, 1.5, 5, 15, 40, 120, 370, 1000, 3000, 10000 nM
Incubation Time:

24 h
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.

Cell Viability Assay^[1]

Cell Line:

mouse macrophagic RAW264.7 cells
Concentration:

2.5, 5, 10, 20 μM
Incubation Time:

24 h
Result:

Exert little effect on the viability of RAW264.7 cells at concentrations up to 10 μM.

Western Blot Analysis^[1]

Cell Line:

LPS-stimulated mouse macrophagic RAW264.7 cells
Concentration:

0.1 μM, 1 μM, 10 μM
Incubation Time:

1 h pre-treatment, followed by 24 h co-incubation with LPS
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.

Real Time qPCR^[1]

Cell Line:

LPS-stimulated mouse macrophagic RAW264.7 cells
Concentration:

0.1 μM, 1 μM, 10 μM
Incubation Time:

2 h pre-treatment followed by 3 h LPS stimulation
Result:

Inhibited the mRNA expression and protein secretion of proinflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW264.7 cells.

ELISA Assay^[1]

Cell Line:

LPS-stimulated mouse macrophagic RAW264.7 cells
Concentration:

0.1 μM, 1 μM, 10 μM
Incubation Time:

3 h co-incubation with LPS
Result:

Inhibited the mRNA expression and protein secretion of proinflammatory cytokines IL-1β and IL-6 in LPS-stimulated RAW264.7 cells.

Parmacokinetics

Species	Dose	Route	AUC_0-t	AUC_0-∞	MRT_0-t	MRT_0-∞	T_1/2	V_z	CL	C_max	F
Rat^[1]	2 mg/kg	i.v.	925.92 μg/L·h	933.81 μg/L·h	1.27 h	1.37 h	1.82 h	5.85 L/kg	2.25 L/h/kg	1894.72 μg/L	/
Rat^[1]	20 mg/kg	p.o.	27.06 μg/L·h	29 μg/L·h	4.95 h	5.23 h	2.12 h	/	/	9.7 μg/L	0.25 %

In Vivo

Innate ImmunityCytokines & Chemokines

Innate Immunity

Cytokines & Chemokines

PROTAC BTK Degrader-6 (compound 15) (10-50 mg/kg; i.p.) dose-dependently inhibits myeloid cell recruitment and the levels of proinflammatory cytokines (IL-1β, IL-6) in a zymosan-induced mouse peritonitis model^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57BL/6J (male, 10-12 weeks old)^[1]
Dosage:

10 mg/kg; 20 mg/kg; 50 mg/kg
Administration:

i.p.; single pretreatment 1 hour prior to zymosan challenge
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.

Related Protocols :

Chemical Information

CAS. Nr. 2767204-39-5
Appearance Solid
Molecular Weight 837.92
Formel C₄₅H₄₇N₁₁O₆
Color Light yellow to yellow
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
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Lösungsmittel & Löslichkeit

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.1934 mL

5.9672 mL

11.9343 mL

5 mM

0.2387 mL

1.1934 mL

2.3869 mL

10 mM

0.1193 mL

0.5967 mL

1.1934 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

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.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (282 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Huang J, et al. Discovery of Ibrutinib-based BTK PROTACs with in vivo anti-inflammatory efficacy by inhibiting NF-κB activation. European journal of medicinal chemistry. 2023 Nov 05;259:115664. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

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PROTAC BTK Degrader-6

Alle PROTACs Isoform-spezifische Produkte anzeigen

Alle NF-κB Isoform-spezifische Produkte anzeigen

Alle Interleukin Related Isoform-spezifische Produkte anzeigen