Cat. No.: HY-189146

HDTAC EGFR Degrader-1

HDTAC EGFR Degrader-1 is an EGFR HDTAC (hypoxia-activated targeted protein degradation chimera) degrader with a DC₅₀ of 1.76 μM. HDTAC EGFR Degrader-1 consists of a linker, a tumor hypoxia-activated group (HAG, a group that generates ROS under tumor hypoxic conditions), and an EGFR ligand. HDTAC EGFR Degrader-1 drives EGFR degradation through the proteasomal pathway. HDTAC EGFR Degrader-1 downregulates Caspase-3 under hypoxic conditions. HDTAC EGFR Degrader-1 can be used in research on non-small cell lung cancer harboring EGFR mutations (EGFR ligand: FAAH-IN-2 (HY-79511); HAG: Thalidomide-O-COOH (HY-103597); linker: NH2-PEG3 (HY-W007545)).

For research use only. We do not sell to patients.

Formula: C₂₈H₂₇ClFN₇O₆
Molecular Weight:612.01

Storage:

Please store the product under the recommended conditions in the Certificate of Analysis.

HDTAC EGFR Degrader-1 Chemical Structure

Price

Stock

Quantity

Amount: USD 0.00

* Please select Quantity before adding items.

Use of MCE Products

One-stop solution for XDC (ADC/PDC/RDC/ApDC/FDC/ISAC/VDC/SMDC)

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- Parmacokinetics
- In Vivo
Chemical Information
Purity & Documentation
References
Calculators
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

^[1]

Caspase 3

All EGFR Isoforms :

All Caspase Isoforms :

All PROTACs Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
PC-9	IC50	1.432 μM	Cytotoxicity against human PC9 lung cancer cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation. Cytotoxicity against human PC9 lung cancer cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation.	42679150
PC-9	IC50	0.197 μM	Cytotoxicity against human PC9 lung cancer cells under hypoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation. Cytotoxicity against human PC9 lung cancer cells under hypoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation.	42679150
HCC4006	IC50	0.852 μM	Cytotoxicity against human HCC4006 lung cancer cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation. Cytotoxicity against human HCC4006 lung cancer cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation.	42679150
HCC4006	IC50	0.052 μM	Cytotoxicity against human HCC4006 lung cancer cells under hypoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation. Cytotoxicity against human HCC4006 lung cancer cells under hypoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation.	42679150
MRC5	IC50	greater than 50 μM	Cytotoxicity against human MRC-5 embryonic lung fibroblast cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation. Cytotoxicity against human MRC-5 embryonic lung fibroblast cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation.	42679150
A549	IC50	13.01 μM	Cytotoxicity against human A549 wild-type EGFR lung cancer cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation. Cytotoxicity against human A549 wild-type EGFR lung cancer cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation.	42679150
A549	IC50	4.40 μM	Cytotoxicity against human A549 wild-type EGFR lung cancer cells under hypoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation. Cytotoxicity against human A549 wild-type EGFR lung cancer cells under hypoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation.	42679150
H1975	IC50	8.65 μM	Cytotoxicity against gefitinib-resistant human H1975 lung cancer cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation. Cytotoxicity against gefitinib-resistant human H1975 lung cancer cells under normoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation.	42679150
H1975	IC50	3.19 μM	Cytotoxicity against gefitinib-resistant human H1975 lung cancer cells under hypoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation. Cytotoxicity against gefitinib-resistant human H1975 lung cancer cells under hypoxia conditions assessed by CCK-8 cell viability assay after 72 h incubation.	42679150
PC-9	DC₅₀	0.20 μM	EGFR degradation in human PC9 EGFRdel19 mutated lung cancer cells under hypoxic conditions after 24 h incubation measured by Western blot assay. EGFR degradation in human PC9 EGFRdel19 mutated lung cancer cells under hypoxic conditions after 24 h incubation measured by Western blot assay.	42679150
PC-9	DC₅₀	4.05 μM	EGFR degradation in human PC9 EGFRdel19 mutated lung cancer cells under normoxic conditions after 24 h incubation measured by Western blot assay. EGFR degradation in human PC9 EGFRdel19 mutated lung cancer cells under normoxic conditions after 24 h incubation measured by Western blot assay.	42679150
HCC4006	DC₅₀	0.03 μM	EGFR degradation in human HCC4006 EGFRdel19 mutated lung cancer cells under hypoxic conditions after 24 h incubation measured by Western blot assay. EGFR degradation in human HCC4006 EGFRdel19 mutated lung cancer cells under hypoxic conditions after 24 h incubation measured by Western blot assay.	42679150
HCC4006	DC₅₀	0.64 μM	EGFR degradation in human HCC4006 EGFRdel19 mutated lung cancer cells under normoxic conditions after 24 h incubation measured by Western blot assay. EGFR degradation in human HCC4006 EGFRdel19 mutated lung cancer cells under normoxic conditions after 24 h incubation measured by Western blot assay.	42679150
H1975	DC₅₀	1.76 μM	EGFR degradation in gefitinib-resistant human H1975 lung cancer cells harboring EGFR T790M mutation under hypoxic conditions after 24 h incubation measured by Western blot assay. EGFR degradation in gefitinib-resistant human H1975 lung cancer cells harboring EGFR T790M mutation under hypoxic conditions after 24 h incubation measured by Western blot assay.	42679150

In Vitro

HDTAC EGFR Degrader-1 (Compound 11f) (72 h) exhibits selective hypoxia-dependent antiproliferative activity across multiple EGFR mutant lung cancer cell lines and very low antiproliferative activity against normal human MRC-5 fibroblasts, with an IC₅₀ greater than 50 μM under normoxia^[1].
HDTAC EGFR Degrader-1 (1 nM-30 μM; 12-48 h) mediates potent, highly selective hypoxia-dependent EGFR degradation in PC9 and HCC4006 cells, achieving >95% maximum EGFR degradation at elevated concentrations with no detected hook effect^[1].
HDTAC EGFR Degrader-1 (1.0 μM; 24 h) does not modulate Bcl-2 expression in PC9 cells under hypoxic conditions^[1].
HDTAC EGFR Degrader-1 (1.0 μM; 24 h) downregulates Caspase-3 protein levels in PC9 cells under hypoxic conditions^[1].

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

Western Blot Analysis^[1]

Cell Line:

PC9 and HCC4006 human EGFRdel19 mutated lung cancer cells
Concentration:

1 nM-30 μM (24 h); 500 nM (12-48 h)
Incubation Time:

12-48 h
Result:

Achieved EGFR degradation DC₅₀ of 0.20 μM (hypoxia) and 4.05 μM (normoxia) in PC9 cells after 24 h, with maximum degradation rate exceeding 95% under hypoxia.
Achieved EGFR degradation DC₅₀ of 0.03 μM (hypoxia) and 0.64 μM (normoxia) in HCC4006 cells after 24 h, with maximum degradation rate >95% under hypoxia.
Reduced EGFR levels to 11% in PC9 cells and 3% in HCC4006 cells at 500 nM under hypoxia.
Showed no hook effect across the full tested concentration range.

Western Blot Analysis^[1]

Cell Line:

Gefitinib-resistant H1975 human lung cancer cells harboring the EGFR T790M mutation
Concentration:

1 nM-20 μM
Incubation Time:

24 h
Result:

Induced dose-dependent EGFR degradation under hypoxic conditions, achieving a DC₅₀ value of 1.76 μM and a maximum degradation rate over 95%.

Parmacokinetics

Species	Dose	Route	T_1/2	C_max	T_max	AUC_0-t	AUC_0-∞	V_ss
Mice^[1]	5 mg/kg	i.v.	1.19 h	218.12 ng/mL	0.20 h	361.75 ng·h/mL	400.95 ng·h/mL	1.72 mL

In Vivo

HDTAC EGFR Degrader-1 (3-10 mg/kg; i.p.; daily for 14 days; 5-10 mg/kg; i.p.; every 2 days for 20 days) achieves potent, dose-dependent in vivo EGFR degradation and significant tumor growth inhibition in PC9 xenograft nude mice while maintaining a favorable safety profile^[1].

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

Animal Model:

BALB/c nude (Female SPF, 55 total animals, acclimatized for 1 week)^[1]
Dosage:

3-10 mg/kg (daily for 14 days); 5-10 mg/kg (every 2 days for 20 days)
Administration:

i.p. (daily for 14 days); i.p. (every 2 days for 20 days)
Result:

Induced robust, dose-dependent in vivo EGFR degradation in PC9 xenograft tumor tissues.
Demonstrated effective tumor growth inhibition, with no notable body weight loss and no observed pathological changes in major organs.
Showed dose-dependent enhancement of tumor growth inhibitory activity under once-daily dosing regimen compared to the every-other-day schedule.

Chemical Information

Molecular Weight 612.01
Formula C₂₈H₂₇ClFN₇O₆
SMILES

COC1=CC2=C(C(NC3=CC=C(C(Cl)=C3)F)=NC=N2)C=C1OCCOCCOCCNC4=[N+](C5=CC=CC=C5[N+]([O-])=N4)[O-]
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

References

[1]. Cheng W, et al. Identification of Tumor Hypoxia-Activated Degradation-Targeting Chimeras. Journal of medicinal chemistry. 2026 Aug 27;69(16):19671-19689.

Calculators

Molarity Calculator

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

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

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.

Product Name:
Cat. No.:
Quantity:
MCE Japan Authorized Agent:

Product Name:
CAS No.:
Species:
Purity:
Quantity:

HDTAC EGFR Degrader-1

All EGFR Isoforms

All Caspase Isoforms

All PROTACs Isoforms