PROTAC HER2 degrader-1
Based on 1 Customer Validation
PROTAC HER2 degrader-1 is a highly selective HER2 PROTAC degrader, with a DC50 of 69 nM and a Dmax of 96%. PROTAC HER2 degrader-1 inhibits HER2-positive cell proliferation and tumor growth through persistent HER2 degradation and potent inhibition of downstream pathways (AKT and ERK). PROTAC HER2 degrader-1 induces apoptosis in BT-474 cells. PROTAC HER2 degrader-1 can be used for research of HER2-positive cancers.
(Pink: HER2 ligand (HY-177009); Blue: Cereblon ligand (HY-W023573); Black: linker).
For research use only. We do not sell to patients.
- 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
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HER2 69 nM (DC50) |
CRBN-DDB1 |
PROTAC HER2 degrader-1 (Compound CH7C4) (0.1-3 μM, 24 hours) can degrade HER2 in BT-474 cells, which is superior to EGFR in A431 cells[1].
PROTAC HER2 degrader-1 (0-10 μM, 72 hours) has no inhibitory effect on A431 cell proliferation at concentrations up to 10 μM in A431 cells[1].
PROTAC HER2 degrader-1 can inhibit the proliferation of HER2-driven breast cancer cell lines BT-474 and SK-BR-3, and gastric cancer cell line NCI-N87, with IC50 values of 0.047 nM, 0.098 nM, and 0.137 nM, respectively[1].
PROTAC HER2 degrader-1 (0-100 nM) induces apoptosis of BT-474 cells and inhibits the G1 phase of the BT-474 cell cycle[1].
PROTAC HER2 degrader-1 (0-1 μM) induces efficient HER2 degradation in BT-474 (DC50 = 69 nM, Dmax = 96%) and NCI-N87 cells (DC50 = 55 nM, Dmax = 94%) in a concentration-dependent manner[1].
PROTAC HER2 degrader-1 (200 nM, 0-24 hours) induces HER2 degradation and inhibits AKT and ERK phosphorylation in BT-474 cells and NCI-N87 cells[1].
PROTAC HER2 degrader-1 (200 nM, 24 h) induces ubiquitination-mediated HER2 degradation in BT-474 cells via the ubiquitin proteasome system (UPS)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:A431 cells
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Concentration:0.1 μM, 0.3 μM, 1 μM, 3 μM
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Incubation Time:24 h
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Result:Induced almost complete degradation of HER2, and a significant hook effect was observed at 3 μM, without significantly affecting EGFR levels in A431 cells.
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Cell Line:BT-474 cells
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Concentration:0 nM, 10 nM, 50 nM, 100 nM
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Incubation Time:
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Result:Induced apoptosis (63% at 50 nM) and inhibited G1 cell cycle (84% at 100 nM) in BT-474 cells.
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Cell Line:BT-474 cells, NCI-N87 cells
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Concentration:10 nM, 100 nM, 250 nM, 1000 nM
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Incubation Time:24 h
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Result:Induced HER2 degradation and blocked signal transduction in a concentration-dependent manner.
Reduced HER2 autophosphorylation.
Inhibited phosphorylation of key HER2 oncogenic-associated kinases AKT and ERK without affecting their protein levels.
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Cell Line:BT-474 cells, NCI–N87 cells
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Concentration:200 nM
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Incubation Time:0 h, 3 h, 6 h, 12 h, 24 h
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Result:Induced significant degradation of HER2 within 3 h.
Induced almost complete degradation of HER2 at 24 h and significantly inhibited AKT and ERK phosphorylation.
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Cell Line:BT-474 cells
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Concentration:200 nM
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Incubation Time:24 h
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Result:Degraded HER2, this degradation was completely inhibited after pretreatment with MLN4924 (HY-70062), MG132 (HY-13259), lenalidomide (HY-A0003), and Tucatinib (HY-16069).
| 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 |
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 bearing BT-474 (i.p., 1 × 107) xenograft tumors[1]
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Dosage:5 mg/kg, 10 mg/kg
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Administration:i.v., once a day, 21days
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Result:Showed weaker antitumor activity than 10 mg/kg Tucatinib at a dose of 5 mg/kg, with TGI values of 47% and 64%, respectively
Showed superior antitumor activity compared with Tucatinib at a dose of 10 mg/kg (TGI: 73% vs. 64%).
Degraded HER2, and no significant side effects or weight loss were observed 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 (272 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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