PROTAC EGFR degrader 4
Based on 1 Customer Validation
PROTAC EGFR degrader 4 is an EGFRdel19 and EGFRL858R/T790M degrader with anti-proliferative activity. PROTAC EGFR degrader 4 induces degradation of mutant EGFR variants via ubiquitination and autophagy. PROTAC EGFR degrader 4 suppresses EGFR pathway signal transduction. PROTAC EGFR degrader 4 induces apoptosis, arrests cell cycle, and suppresses cell colony formation in cancer cells. PROTAC EGFR degrader 4 can be used for the research of non-small cell lung cancer.
(Pink: EGFRdel19 and EGFRL858R/T790M Target protein ligand; Blue: VHL ligand (HY-125845); Black: linker (HY-W007714)).
For research use only. We do not sell to patients.
- Purity: 99.70%
- CAS No.: 2882845-50-1
- Formula: C55H70N12O4S
- Molecular Weight:995.29
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Storage:
4°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
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
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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EGFRL858R/T790M |
EGFRdel19 |
VHL |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A-431 | IC50 |
245 nM
Compound: P3
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Antiproliferative activity against human A431 cells expressing wild type EGFR assessed as cell growth inhibition measured after 72 hrs by MTT assay
Antiproliferative activity against human A431 cells expressing wild type EGFR assessed as cell growth inhibition measured after 72 hrs by MTT assay
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[PMID: 32883633] |
| HCC827 | IC50 |
0.76 nM
Compound: P3
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Antiproliferative activity against human HCC827 cells expressing EGFR del19 mutant assessed as cell growth inhibition measured after 72 hrs by MTT assay
Antiproliferative activity against human HCC827 cells expressing EGFR del19 mutant assessed as cell growth inhibition measured after 72 hrs by MTT assay
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[PMID: 32883633] |
| HCC827 | IC50 |
0.76 nM
Compound: 4
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Antiproliferative activity against human HCC827 cells expressing EGFR deletion19 mutant assessed as inhibition of cell proliferation
Antiproliferative activity against human HCC827 cells expressing EGFR deletion19 mutant assessed as inhibition of cell proliferation
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[PMID: 35254067] |
| HepG2 | IC50 |
>5000 nM
Compound: P3
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Antiproliferative activity against human HepG2 cells expressing VEGFR2 assessed as cell growth inhibition measured after 72 hrs by MTT assay
Antiproliferative activity against human HepG2 cells expressing VEGFR2 assessed as cell growth inhibition measured after 72 hrs by MTT assay
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[PMID: 32883633] |
| NCI-H1975 | IC50 |
203 nM
Compound: P3
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Antiproliferative activity against human H1975 cells expressing EGFR L858R/T790M mutant assessed as cell growth inhibition measured after 72 hrs by MTT assay
Antiproliferative activity against human H1975 cells expressing EGFR L858R/T790M mutant assessed as cell growth inhibition measured after 72 hrs by MTT assay
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[PMID: 32883633] |
| NCI-H1975 | IC50 |
203 nM
Compound: 4
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Antiproliferative activity against human NCI-H1975 cells expressing EGFR L858R/T790M mutant assessed as inhibition of cell proliferation
Antiproliferative activity against human NCI-H1975 cells expressing EGFR L858R/T790M mutant assessed as inhibition of cell proliferation
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[PMID: 35254067] |
PROTAC EGFR degrader 4 (P3) potently inhibits proliferation of HCC827 cells (IC50 = 0.83 nM), inhibits H1975 cells (IC50 = 203 nM), shows submicromolar activity against A431 cells, and is inactive against HepG2 cells[1].
PROTAC EGFR degrader 4 (0.3-1000 nM; 6-72 h) induces time- and concentration-dependent degradation of EGFRdel19 in HCC827 cells with a DC50 of 0.51 nM, achieves maximum degradation at 48 h, and has a long-lasting effect that persists for 24 h after washout[1].
PROTAC EGFR degrader 4 (0.033-3.3 μM; 48 h) induces degradation of EGFRL858R/T790M in H1975 cells with a DC50 of 126.2 nM, shows negligible activity against EGFRWT in A431 cells, and maintains suppression of EGFRL858R/T790M levels for 48 h after washout[1].
PROTAC EGFR degrader 4 (3 nM in HCC827, 100 nM in H1975) inhibits EGFR pathway signal transduction by reducing phosphorylated EGFR and phosphorylated Akt levels in HCC827 and H1975 cells, while preserving total Akt levels[1].
PROTAC EGFR degrader 4 (0.033 μM; 24 h, with 2 h inhibitor preincubation)-induced EGFRdel19 degradation in HCC827 cells requires ubiquitination and ternary complex formation with VHL, and is partially dependent on the autophagic-lysosomal system[1].
PROTAC EGFR degrader 4 (10-100 nM in HCC827, 333-1000 nM in H1975; 48 h) induces apoptosis in HCC827 cells in a concentration-dependent manner, but does not significantly induce apoptosis in H1975 cells[1].
PROTAC EGFR degrader 4 (10-100 nM in HCC827, 333-1000 nM in H1975; 48 h) induces G1 phase cell cycle arrest in both HCC827 and H1975 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCC827 (EGFRdel19), H1975 (EGFRL858R/T790M), A431 (EGFRWT), HepG2 (VEGFR2)
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Concentration:series of concentrations
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Incubation Time:72 h
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Result:Potently inhibited proliferation of HCC827 cells with an IC50 of 0.83 nM.
Inhibited H1975 cell proliferation with an IC50 of 203 nM.
Showed submicromolar activity against A431 cells with an IC50 of 245 nM.
Had no significant activity against HepG2 cells (IC50 > 5000 nM).
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Cell Line:HCC827 (EGFRdel19)
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Concentration:33 nM (time-course/washout); 0.3-1000 nM (48 h)
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Incubation Time:6-72 h (33 nM); 48 h (0.3-1000 nM); 24 h followed by 24-48 h washout
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Result:Induced time-dependent degradation of EGFRdel19, with maximum effect achieved at 48 h.
Had a DC50 of 0.51 nM and maximum degradation rate (Dmax) of 80.4% for EGFRdel19 degradation.
Suppressed EGFRdel19 levels 24 h after washout, and levels almost recovered by 48 h post-washout.
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Cell Line:H1975 (EGFRL858R/T790M), A431 (EGFRWT)
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Concentration:0.033-3.3 μM (48 h in H1975); 0.1-3.3 μM (48 h in A431); 333 nM (washout in H1975)
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Incubation Time:48 h; 48 h followed by 24-48 h washout (H1975)
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Result:Induced degradation of EGFRL858R/T790M in H1975 cells with a DC50 of 126.2 nM and Dmax of 90.3%.
Showed almost no degradation of EGFRWT in A431 cells.
Suppressed EGFRL858R/T790M levels for 48 h after washout.
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Cell Line:HCC827
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Concentration:0.033 μM (PROTAC EGFR degrader 4); 10 μM MLN4924; 10 μM VHL-Ac; 10 μM chloroquine
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Incubation Time:24 h (PROTAC EGFR degrader 4); 2 h (preincubation with inhibitors)
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Result:Blocked EGFRdel19 degradation induced by P3 when pretreated with ubiquitination inhibitor MLN4924.
Attenuated P3-induced EGFRdel19 degradation when pretreated with acetylated VHL ligand (VHL-Ac).
Slightly impaired P3-induced EGFRdel19 degradation when pretreated with autophagy inhibitor chloroquine.
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Cell Line:HCC827, H1975
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Concentration:0.1-0.3 nM (HCC827); 100-333 nM (H1975); 0.1 μM P3, 0-30 μM rapamycin (H1975)
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Incubation Time:16 h (PROTAC EGFR degrader 4); 8 h (preincubation with rapamycin or serum deprivation)
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Result:Enhanced P3-induced degradation of EGFRdel19 in HCC827 and EGFRL858R/T790M in H1975 cells under serum deprivation, with corresponding increases in LC3-II/I ratio and decreases in p62 levels confirming enhanced autophagy.
Accelerated P3-induced degradation of EGFRL858R/T790M in H1975 cells when pretreated with rapamycin.
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Cell Line:HCC827, H1975
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Concentration:10-100 nM (HCC827); 333-1000 nM (H1975)
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Incubation Time:48 h
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Result:Induced apoptosis in 31.07% and 44.80% of HCC827 cells at 10 nM and 100 nM, respectively.
Did not induce significant apoptosis in H1975 cells at tested concentrations.
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Cell Line:HCC827, H1975
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Concentration:10-100 nM (HCC827); 333-1000 nM (H1975)
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Incubation Time:48 h
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Result:Arrested both HCC827 and H1975 cell lines at the G1 phase.
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Cell Line:HCC827, H1975
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Concentration:1-100 nM (HCC827); 33-3333 nM (H1975)
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Incubation Time:15 days
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Result:Significantly inhibited colony formation of HCC827 cells at concentrations as low as 1 nM, with dose-dependent reduction in colony formation rate.
Significantly inhibited colony formation of H1975 cells at concentrations as low as 100 nM, with dose-dependent reduction in colony formation rate.
Chemical Information
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CAS No. 2882845-50-1
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Appearance Solid
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Molecular Weight 995.29
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Formula C55H70N12O4S
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Color White to off-white
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SMILES
CC1=C(SC=N1)C2=CC=C(C=C2)CNC([C@@H]3C[C@H](CN3C([C@H](C(C)(C)C)NC(CCCCCCN4CCN(CC4)C5=CC=C(C=C5)NC6=NC=C7N=C(N(C7=N6)C8CCCC8)NC9=CC=CC=C9)=O)=O)O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, protect from light, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)
Solvent & Solubility
DMSO : 100 mg/mL (100.47 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (281 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
Complete Stock Solution Preparation Table
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.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.0047 mL | 5.0237 mL | 10.0473 mL | 25.1183 mL |
| 5 mM | 0.2009 mL | 1.0047 mL | 2.0095 mL | 5.0237 mL | |
| 10 mM | 0.1005 mL | 0.5024 mL | 1.0047 mL | 2.5118 mL | |
| 15 mM | 0.0670 mL | 0.3349 mL | 0.6698 mL | 1.6746 mL | |
| 20 mM | 0.0502 mL | 0.2512 mL | 0.5024 mL | 1.2559 mL | |
| 25 mM | 0.0402 mL | 0.2009 mL | 0.4019 mL | 1.0047 mL | |
| 30 mM | 0.0335 mL | 0.1675 mL | 0.3349 mL | 0.8373 mL | |
| 40 mM | 0.0251 mL | 0.1256 mL | 0.2512 mL | 0.6280 mL | |
| 50 mM | 0.0201 mL | 0.1005 mL | 0.2009 mL | 0.5024 mL | |
| 60 mM | 0.0167 mL | 0.0837 mL | 0.1675 mL | 0.4186 mL | |
| 80 mM | 0.0126 mL | 0.0628 mL | 0.1256 mL | 0.3140 mL | |
| 100 mM | 0.0100 mL | 0.0502 mL | 0.1005 mL | 0.2512 mL |
PROTAC EGFR degrader 4 Related Classifications
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