Gefitinib-based PROTAC 3

Gefitinib-based PROTAC 3 is a proteolysis-targeting chimera (PROTAC) comprised of the EGF receptor (EGFR) inhibitor gefitinib (Cay-13166) linked to the von Hippel-Lindau (VHL) E3 ubiquitin ligase ligand VHL ligand 1 (Cay-21591). In cell-based assays, gefitinib-based PROTAC 3 induces degradation of EGFR containing the activating mutation L858R or an exon 19 deletion with half-maximal degradation (DC50) values of 22.3 and 11.7 nM, respectively, but does not induce degradation of wild-type EGFR at concentrations up to 10 µM.Formal 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. CAS Number: 2230821-27-7. Synonyms: Gefitinib-based Proteolysis-targeting Chimera 3. Molecular Formula: C47H57ClFN7O8S. Formula Weight: 934.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMF:PBS (pH 7.2) (1:3): 0.25 mg/ml, DMSO: 16 mg/ml, Ethanol: 10 mg/ml. lambdamax: 252, 332 nm. SMILES: ClC1=CC(NC2=NC=NC3=C2C=C(OCCCCCOCCOCCC(N[C@@H](C(C)(C)C)C(N4C[C@H](O)C[C@H]4C(NCC5=CC=C(C6=C(C)N=CS6)C=C5)=O)=O)=O)C(OC)=C3)=CC=C1F. InChi Code: 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. InChi Key: NICKHWYZMNLEPJ-TZSMONEZSA-N.