Art. -Nr.: HY-144605

PROTAC EGFR degrader 3

Name: PROTAC EGFR degrader 3
Brand: MedChemExpress
SKU: HY-144605
Price: 860.00 USD
Availability: InStock
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PROTAC EGFR degrader 3 is a selective EGFR mutant PROTAC degrader with activity against EGFR^L858R/T790M and EGFR^del19, with DC₅₀ values of 1.56 nM and 0.49 nM, respectively. PROTAC EGFR degrader 3 induces degradation via formation of a ternary complex with VHL, ubiquitination, and lysosomal processing. PROTAC EGFR degrader 3 inhibits tumor cell proliferation. PROTAC EGFR degrader 3 can be used for the research of non-small cell lung cancer.
(Pink: EGFR ligand (HY-150905); Blue: ligand (HY-112078); Black: linker).

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Reinheit : 97.39%
CAS. Nr.: 2768472-28-0
Formel: C₆₀H₇₇N₁₃O₅S
Molecular Weight:1092.40

Speicherung:

4°C, protect from light, stored under nitrogen

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

PROTAC EGFR degrader 3 Chemical Structure

CAS. Nr.: 2768472-28-0

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Biologische Aktivität
- Beschreibung
- Cellular Effect
- In Vitro
Chemical Information
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

PROTAC EGFR degrader 3 is a selective EGFR mutant PROTAC degrader with activity against EGFR^L858R/T790M and EGFR^del19, with DC₅₀ values of 1.56 nM and 0.49 nM, respectively. PROTAC EGFR degrader 3 induces degradation via formation of a ternary complex with VHL, ubiquitination, and lysosomal processing. PROTAC EGFR degrader 3 inhibits tumor cell proliferation. PROTAC EGFR degrader 3 can be used for the research of non-small cell lung cancer^[1]. (Pink: EGFR ligand (HY-150905); Blue: ligand (HY-112078); Black: linker).

Alle EGFR Isoform-spezifische Produkte anzeigen :

Alle PROTACs Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
A-431	IC₅₀	>10000 nM Compound: CP17	Antiproliferative activity against human A-431 cells expressing EGFR wildtype assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay Antiproliferative activity against human A-431 cells expressing EGFR wildtype assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay	[PMID: 35254067]
BaF3	IC₅₀	481 nM Compound: CP17	Antiproliferative activity against mouse BaF3 cells expressing EGFR deletion19/T790M/C797S mutant assessed as reduction on cell growth incubated for 72 hrs by MTT assay Antiproliferative activity against mouse BaF3 cells expressing EGFR deletion19/T790M/C797S mutant assessed as reduction on cell growth incubated for 72 hrs by MTT assay	[PMID: 35254067]
BaF3	IC₅₀	669 nM Compound: CP17	Antiproliferative activity against mouse BaF3 cells expressing EGFR L858R/T790M/C797S mutant assessed as reduction on cell growth incubated for 72 hrs by MTT assay Antiproliferative activity against mouse BaF3 cells expressing EGFR L858R/T790M/C797S mutant assessed as reduction on cell growth incubated for 72 hrs by MTT assay	[PMID: 35254067]
HCC827	IC₅₀	1.6 nM Compound: CP17	Antiproliferative activity against human HCC827 cells expressing EGFR deletion19 mutant assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay Antiproliferative activity against human HCC827 cells expressing EGFR deletion19 mutant assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay	[PMID: 35254067]
HCC827	IC₅₀	1.6 nM Compound: CP17	Antiproliferative activity against human HCC827 cells expressing EGFR L858R/T790M mutant assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay Antiproliferative activity against human HCC827 cells expressing EGFR L858R/T790M mutant assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay	[PMID: 35254067]
NCI-H1975	IC₅₀	32 nM Compound: CP17	Antiproliferative activity against human NCI-H1975 cells expressing EGFR L858R/T790M mutant assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay Antiproliferative activity against human NCI-H1975 cells expressing EGFR L858R/T790M mutant assessed as inhibition of cell proliferation incubated for 72 hrs by MTT assay	[PMID: 35254067]
NCI-H1975	IC₅₀	>10000 nM Compound: CP17	Antiproliferative activity against human NCI-H1975 cells expressing EGFR L858R/T790M/C797S mutant assessed as reduction on cell growth incubated for 72 hrs by MTT assay Antiproliferative activity against human NCI-H1975 cells expressing EGFR L858R/T790M/C797S mutant assessed as reduction on cell growth incubated for 72 hrs by MTT assay	[PMID: 35254067]
PC-9	IC₅₀	>10000 nM Compound: CP17	Antiproliferative activity against human PC-9 cells expressing EGFR deletion19/T790M/C797S mutant assessed as reduction on cell growth growth incubated for 72 hrs by MTT assay Antiproliferative activity against human PC-9 cells expressing EGFR deletion19/T790M/C797S mutant assessed as reduction on cell growth growth incubated for 72 hrs by MTT assay	[PMID: 35254067]

In Vitro

Anti-cancer

PROTAC EGFR degrader 3 (compound CP17) (72 h) potently inhibits the proliferation of H1975 (EGFR^L858R/T790M) and HCC827 (EGFR^del19) cells, with IC₅₀ values of 32 nM and 1.60 nM, respectively, but shows weak activity against cells harboring EGFR triple mutants and wild-type EGFR^[1].
PROTAC EGFR degrader 3 (1-1000 nM, H1975 cells; 0.3-30 nM, HCC827 cells; 10 days) potently inhibits colony formation of H1975 (EGFR^L858R/T790M) and HCC827 (EGFR^del19) cells at concentrations as low as 30 nM and 1 nM, respectively^[1].
PROTAC EGFR degrader 3 (0.3-1000 nM; 2-72 h) potently and selectively degrades EGFR^L858R/T790M (DC₅₀ = 1.56 nM) in H1975 cells and EGFR^del19 (DC₅₀ = 0.49 nM) in HCC827 cells, with the maximum degradation effect achieved after 48 h of treatment^[1].
PROTAC EGFR degrader 3 (0.3-1000 nM, H1975 cells; 0.3-30 nM, HCC827 cells; 24 h) effectively blocks the EGFR signaling pathway in H1975 (EGFR^L858R/T790M) and HCC827 (EGFR^del19) cells by inhibiting the phosphorylation of EGFR, AKT and ERK1/2^[1].
PROTAC EGFR degrader 3 (30 nM; 24 h, then analyzed at 12, 24, 48 h post-washout) exerts more durable degradation of EGFR^del19 in HCC827 cells than of EGFR^L858R/T790M in H1975 cells; at 48 h post-washout, the expression level of EGFR^del19 remains reduced, while that of EGFR^L858R/T790M is restored^[1].
PROTAC EGFR degrader 3 (30 nM; with pre-treatment inhibitors) induces the degradation of EGFR^L858R/T790M in H1975 cells. This process depends on the formation of a ternary complex involving EGFR and VHL, as well as ubiquitination, and is associated with the lysosomal pathway but not the proteasomal pathway^[1].

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

Cell Proliferation Assay^[1]

Cell Line:

H1975 cells (EGFRL858R/T790M), HCC827 cells (EGFRdel19)
Concentration:

1, 10, 30, 100, 1000 nM (H1975 cells); 0.3, 1, 3, 10, 30 nM (HCC827 cells)
Incubation Time:

10 days
Result:

Significantly reduced colony formation rate in a dose-dependent manner for both cell lines.
Reduced H1975 and HCC827 colony formation rate.

Western Blot Analysis^[1]

Cell Line:

H1975 cells (EGFRL858R/T790M), HCC827 cells (EGFRdel19), A431 cells (EGFRWT), HCT116 cells, HeLa cells, MCF-7 cells, HepG2 cells
Concentration:

10, 100 nM (H1975 cells, 24 h)
3, 30 nM (HCC827 cells, 24 h)
0.3, 1, 3, 10, 30, 100, 300, 1000 nM (H1975 cells, 48 h)
0.3, 1, 3, 10, 30, 100, 300 nM (HCC827 cells, 24 h)
30 nM (H1975 cells, time-course)
10, 30, 100, 300, 1000 nM (A431 cells, 24 h)
100, 1000 nM (HCT116, HeLa, MCF-7, HepG2 cells, 24 h)
Incubation Time:

2, 4, 8, 12, 24, 36, 48, 72 h (H1975 cells, time-course)
24 h (H1975, HCC827, A431, HCT116, HeLa, MCF-7, HepG2 cells)
48 h (H1975, HCC827 cells)
Result:

Induced 51% degradation of EGFRL858R/T790M at 10 nM and 77% degradation at 100 nM in H1975 cells after 24 h.
Induced 70% degradation of EGFRdel19 at 3 nM and 74% degradation at 30 nM in HCC827 cells after 24 h.
Achieved a DC₅₀ of 1.56 nM for EGFRL858R/T790M degradation in H1975 cells, with a maximum degradation rate of 86% after 48 h.
Achieved a DC₅₀ of 0.49 nM for EGFRdel19 degradation in HCC827 cells, with a maximum degradation rate of 82%.
Caused significant degradation of EGFRL858R/T790M after 8 h of treatment with 30 nM CP17, peaking at 48 h.
Did not induce significant degradation of EGFRWT in A431 cells at concentrations up to 1000 nM.
Induced minimal degradation in HCT116, HeLa, and HepG2 cells at 1000 nM, with no effect in MCF-7 cells.

Western Blot Analysis^[1]

Cell Line:

H1975 cells (EGFRL858R/T790M), HCC827 cells (EGFRdel19)
Concentration:

0.3, 1, 10, 100, 1000 nM (H1975 cells)
0.3, 1, 3, 10, 30 nM (HCC827 cells)
Incubation Time:

24 h
Result:

Significantly reduced levels of phosphorylated EGFR, AKT, and ERK1/2 in both cell lines, while leaving phosphorylated B-RAF levels unchanged.
Caused significant inhibition in H1975 cells at 100 nM.
Caused significant inhibition in HCC827 cells at 3 nM.

Western Blot Analysis^[1]

Cell Line:

H1975 cells (EGFRL858R/T790M), HCC827 cells (EGFRdel19)
Concentration:

30 nM
Incubation Time:

24 h, then analyzed at 12, 24, 48 h post-washout
Result:

Caused EGFRL858R/T790M and phosphorylated EGFRL858R/T790M levels to significantly recover 48 h after washout.
Left EGFRdel19 and phosphorylated EGFRdel19 levels reduced even 48 h after washout.

Related Protocols :

Chemical Information

CAS. Nr. 2768472-28-0
Appearance Solid
Molecular Weight 1092.40
Formel C₆₀H₇₇N₁₃O₅S
Color Off-white to light yellow
SMILES

C=CC(N1CCC[C@@H](C1)N2C3=C(N=C2NC4=CC=CC=C4)C=NC(NC5=CC=C(C=C5)N6CCN(CC6)CCCCCCCC(N[C@H](C(N7[C@@H](C[C@H](C7)O)C(N[C@H](C8=CC=C(C=C8)C9=C(N=CS9)C)C)=O)=O)C(C)(C)C)=O)=N3)=O
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

4°C, protect from light, stored under nitrogen

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 100 mg/mL (91.54 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

0.9154 mL

4.5771 mL

9.1542 mL

5 mM

0.1831 mL

0.9154 mL

1.8308 mL

10 mM

0.0915 mL

0.4577 mL

0.9154 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 (protect from light, 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.

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 (2.29 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% Corn Oil

Solubility: ≥ 2.5 mg/mL (2.29 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, 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 (277 KB)
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)
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]. Zhao HY, et al. Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands. Journal of medicinal chemistry. 2022 Mar 24;65(6):4709-4726. [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

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	0.9154 mL	4.5771 mL	9.1542 mL	22.8854 mL
	5 mM	0.1831 mL	0.9154 mL	1.8308 mL	4.5771 mL
	10 mM	0.0915 mL	0.4577 mL	0.9154 mL	2.2885 mL
	15 mM	0.0610 mL	0.3051 mL	0.6103 mL	1.5257 mL
	20 mM	0.0458 mL	0.2289 mL	0.4577 mL	1.1443 mL
	25 mM	0.0366 mL	0.1831 mL	0.3662 mL	0.9154 mL
	30 mM	0.0305 mL	0.1526 mL	0.3051 mL	0.7628 mL
	40 mM	0.0229 mL	0.1144 mL	0.2289 mL	0.5721 mL
	50 mM	0.0183 mL	0.0915 mL	0.1831 mL	0.4577 mL
	60 mM	0.0153 mL	0.0763 mL	0.1526 mL	0.3814 mL
	80 mM	0.0114 mL	0.0572 mL	0.1144 mL	0.2861 mL

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PROTAC EGFR degrader 3

Alle EGFR Isoform-spezifische Produkte anzeigen

Alle PROTACs Isoform-spezifische Produkte anzeigen