PROTAC HER2 degrader-1
Based on 1 Customer Validation
PROTAC HER2 degrader-1 is a selective HER2 PROTAC degrader with a DC50 of 69 nM. PROTAC HER2 degrader-1 induces ubiquitination and degradation of HER2 via the ubiquitin-proteasome system, thereby inhibiting the downstream PI3K/AKT/mTOR and RAS/RAF/MEK/ERK signaling pathways. PROTAC HER2 degrader-1 inhibits the proliferation of HER2-positive cancer cells, induces apoptosis and arrests the cell cycle. PROTAC HER2 degrader-1 suppresses the growth of HER2-positive xenografts. PROTAC HER2 degrader-1 can be used in HER2-positive cancer-related research.
(Pink: HER2 ligand (HY-177009); Blue: Cereblon ligand (HY-W023573); Black: linker).
For research use only. We do not sell to patients.
- Purity: 98%
- CAS No.: 2897640-93-4
- Formula: C49H55N11O7
- Molecular Weight:910.03
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Storage:Powder -20°C, 3 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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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
HER2 69 nM (DC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| BT-474 | IC50 |
0.047 nM
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Antiproliferative activity against human HER2-positive BT-474 cancer cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human HER2-positive BT-474 cancer cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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36208507 |
| SK-BR-3 | IC50 |
0.098 nM
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Antiproliferative activity against human HER2-positive SK-BR-3 cancer cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human HER2-positive SK-BR-3 cancer cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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36208507 |
| NCI-N87 | IC50 |
0.137 nM
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Antiproliferative activity against human HER2-positive NCI-N87 cancer cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human HER2-positive NCI-N87 cancer cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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36208507 |
| BT-474 | DC50 |
69 nM
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Induction of HER2 protein degradation in human HER2-positive BT-474 cancer cells measured by Western blot assay.
Induction of HER2 protein degradation in human HER2-positive BT-474 cancer cells measured by Western blot assay.
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36208507 |
| NCI-N87 | DC50 |
55 nM
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Induction of HER2 protein degradation in human HER2-positive NCI-N87 cancer cells measured by Western blot assay.
Induction of HER2 protein degradation in human HER2-positive NCI-N87 cancer cells measured by Western blot assay.
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36208507 |
In Vitro
PROTAC HER2 degrader-1 (CH7C4) potently and selectively inhibits the activity of purified HER2 kinase with an IC50 of 48.65 nM, while it exhibits much weaker inhibitory activity against EGFR kinase with an IC50 of 4383 nM. It potently suppresses the proliferation of HER2-positive BT-474, SK-BR-3 and NCI-N87 cancer cells, with IC50 values of 0.047 nM, 0.098 nM and 0.137 nM, respectively[1].
PROTAC HER2 degrader-1 (0.078-10 μM; 72 h) does not inhibit the proliferation of EGFR-driven A431 cells[1].
PROTAC HER2 degrader-1 (0.1-1000 nM; 1-24 h) efficiently induces concentration- and time-dependent HER2 degradation in BT-474 cells, with a DC50 of 69 nM and a Dmax of 96%; it also induces such degradation in NCI-N87 cells, with a DC50 of 55 nM and a Dmax of 94%[1].
PROTAC HER2 degrader-1 (10-1000 nM; 0-24 h) potently and persistently inhibits the PI3K/AKT and RAS/RAF/ERK signaling pathways downstream of HER2 in BT-474 and NCI-N87 cells by inducing HER2 degradation[1].
PROTAC HER2 degrader-1 (200 nM; 24 h) induces HER2 degradation in BT-474 cells via a ubiquitin-proteasome system-dependent mechanism. This process is blocked by UPS inhibitors, CRBN ligands and HER2 inhibitors, and is completely abolished by methylation of this agent[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:EGFR-driven A431 cancer cell line
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Concentration:0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10 μM
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Incubation Time:72 h
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Result:Exhibited no significant inhibition of A431 cell viability at concentrations up to 10 μM.
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Cell Line:BT-474 and NCI-N87 cancer cell lines
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Concentration:10, 50, 100, 250, 500, 1000 nM (concentration-dependent degradation)
200 nM (time-course degradation)
500 nM (24 h incubation) -
Incubation Time:1, 3, 6, 12, 24 h (time-course degradation)
24 h (concentration-dependent and fixed-concentration incubation) -
Result:Induced concentration-dependent HER2 degradation with a DC50 of 69 nM and Dmax of 96% in BT-474 cells.
Induced concentration-dependent HER2 degradation with a DC50 of 55 nM and Dmax of 94% in NCI-N87 cells.
Caused significant HER2 degradation within 3 h of treatment with 200 nM.
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Cell Line:BT-474 and NCI-N87 cancer cell lines
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Concentration:10, 100, 250, 1000 nM (24 h incubation)
200 nM (24 h incubation with wash-out) -
Incubation Time:24 h (incubation)
0, 3, 6, 12, 24 h (wash-out culture) -
Result:Induced concentration-dependent reduction in HER2 autophosphorylation, and phosphorylation of AKT and ERK1/2, without altering total AKT or ERK1/2 protein levels in both cell lines.
Sustained HER2 degradation and inhibition of AKT/ERK phosphorylation for over 12 h after 24 h treatment with 200 nM followed by wash-out.
Showed no significant HER2 rebound until 24 h after wash-out.
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Cell Line:BT-474 cancer cell lines
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Concentration:200 nM (co-treated with inhibitors); 1 μM methylated CH7C4
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Incubation Time:2 h (pre-treatment); 24 h (co-treatment and methylated CH7C4 incubation)
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Result:Had HER2 degradation completely blocked by pre-treatment with 1 μM MLN4924 (HY-70062), 1 μM MG132 (HY-13259), 1 μM cereblon ligand, or 1 μM human epidermal growth factor receptor 2 inhibitor.
Parmacokinetics
| Species | Dose | Route | AUCinf | T1/2 | CL | Vss | AUCall |
|---|---|---|---|---|---|---|---|
| Rat | 2 mg/kg | i.p. | 3214 ng·h/mL | 5.31 h | 12.1 mL/min/kg | 1048 mL/kg | 3089 ng·h/mL |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (6‑week‑old female) were firstly subcutaneously inoculated with 1 × 107 BT‑474 cells.
Tumor fragments (20‑100 mg) from primary tumors were re‑implanted into new mice. -
Dosage:5 mg/kg; 10 mg/kg
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Administration:i.v.; daily; 21 days
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Result:Achieved a tumor growth inhibition (TGI) of 47%.
Achieved a tumor growth inhibition (TGI) of 73%.
Confirmed significant HER2 degradation in vivo via western blot analysis of tumor tissues.
Caused no significant side effects or weight loss during treatment.
Chemical Information
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CAS No. 2897640-93-4
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Appearance Solid
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Molecular Weight 910.03
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Formula C49H55N11O7
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Color Light yellow to yellow
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SMILES
O=C1C2=CC=C(NCCCCCCCN3CCN(CCCOC4=CC5=NC=NC(NC6=CC=C(C(C)=C6)OC7=CC8=NC=NN8C=C7)=C5C=C4OC)CC3)C=C2C(N1C9C(NC(CC9)=O)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Purity & Documentation
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Data Sheet (278 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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC HER2 degrader-1 Related Classifications
HY-177008 Related Classifications
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