Gefitinib-based PROTAC 3

NTN21277, also known as Gefitinib-based PROTAC 3 is a VHL-recruiting PROTAC that induces the degradation of EGFR and EGFR mutants with DC50 of 11.7 nM and 22.3 nM for HCC827 cell (Exon 19 del) and H3255 cell (L858R).

Product information

CAS Number: 2230821-27-7

Molecular Weight: 934.51

Formula: C47H57ClFN7O8S

Synonym:

NTN-21277

Gefitinib-based PROTAC 3

NTN21277

NTN 21277

Chemical Name: (2S,4R)-1-((S)-2-(3-(2-((5-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)pentyl)oxy)ethoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

Smiles: CC1N=CSC=1C1C=CC(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCOCCOCCCCCOC2=CC3=C(NC4=CC(Cl)=C(F)C=C4)N=CN=C3C=C2OC)C(C)(C)C)=CC=1

InChiKey: NICKHWYZMNLEPJ-TZSMONEZSA-N

InChi: InChI=1S/C47H57ClFN7O8S/c1-29-42(65-28-53-29)31-11-9-30(10-12-31)25-50-45(59)38-22-33(57)26-56(38)46(60)43(47(2,3)4)55-41(58)15-18-63-20-19-62-16-7-6-8-17-64-40-23-34-37(24-39(40)61-5)51-27-52-44(34)54-32-13-14-36(49)35(48)21-32/h9-14,21,23-24,27-28,33,38,43,57H,6-8,15-20,22,25-26H2,1-5H3,(H,50,59)(H,55,58)(H,51,52,54)/t33-,38+,43-/m1/s1

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

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.

References:

1. Burslem GM, et al. The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study. Cell Chem Biol. 2018 Jan 18;25(1):67-77.e3.

Products are for research use only. Not for human use.