Gefitinib-based PROTAC 3

SKU: orb1301790

Description

This bifunctional PROTAC molecule, designated as compound 3, utilizes a gefitinib-derived warhead to target EGFR and a VHL ligand to recruit the cellular degradation machinery. It potently induces degradation of mutant EGFR proteins in NSCLC cell lines, including HCC827 (exon 19 del) and H3255 (L858R), with DC50 values in the low nanomolar range. This tool compound is valuable for probing targeted protein degradation in oncology research, both in vitro and in vivo.

Research Area

Cardiovascular Research, Pharmacology & Drug Discovery, Signal Transduction

Key Properties

• CAS Number: 2230821-27-7
• MW: 934.51
• Purity: 98.25% (May vary between batches)
• Formula: C₄₇H₅₇ClFN₇O₈S
• SMILES: N(C=1C2=C(C=C(OC)C(OCCCCCOCCOCCC(N[C@H](C(=O)N3[C@H](C(NCC4=CC=C(C=C4)C=5SC=NC5C)=O)C[C@@H](O)C3)[C@](C)(C)C)=O)=C2)N=CN1)C6=CC(Cl)=C(F)C=C6
• Target: PROTACs,EGFR
• Solubility: DMSO:10 mM

Bioactivity

• Target IC50:
  EGFR:11.7 nM (DC50, HCC827(exon 19 del) cells)|EGFR:22.3 nM (DC50, H3255 (L858R mutantion) cells)
• In Vitro:
  H3255 cells expressing L858R EGFR treated with Gefitinib-based PROTAC 3 (25 nM-10 μM; 24 hours), HCC827 cells expressing exon 19 del EGFR treated with Gefitinib-based PROTAC 3 (100 nM-10 μM; 24 hours), which enables the degradation of both exon-19 deletion EGFR as well as the mutant isoform containing the L858R activating point mutation, while sparing the WT EGFR.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, Gefitinib based PROTAC 3, Gefitinibbased PROTAC 3, Gefitinib-based PROTAC 3, HER1, ErbB-1, EGFR, Epidermal growth factor receptor, inhibit, PROTACs

Compound Identifiers

PubChem CID

135156947