NTN21277(Gefitinib-based PROTAC 3)|CAS 2230821-27-7|DC Chemicals

Cas No.:	2230821-27-7
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
Synonyms:	NTN21277;NTN-21277;NTN 21277
SMILES:	N(C(=O)[C@H](NC(=O)CCOCCOCCCCCOC1C(OC)=CC2C(C=1)=C(NC1=CC=C(F)C(Cl)=C1)N=CN=2)C(C)(C)C)1C[C@@H](O)C[C@@H]1C(NCC1=CC=C(C2SC=NC=2C)C=C1)=O
Formula:	C₄₇H₅₇ClFN₇O₈S
M.Wt:	934.522
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	[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.

Description:	Gefitinib-based PROTAC 3, conjugating an EGFR binding element to a VHL ligand via a linker, induces EGFR degradation with DC50s of 11.7 nM and 22.3 nM in HCC827(exon 19 del) and H3255 (L858R mutantion) cells, respectively[1].
Target:	EGFR:11.7 nM (DC50, HCC827(exon 19 del) cells) EGFR:22.3 nM (DC50, H3255 (L858R mutantion) cells) PROTAC
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[1]. Western Blot Analysis[1] Cell Line: HCC827 cells expressing exon 19 del EGFR; H3255 cells expressing L858R EGFR Concentration: 100 nM, 250 nM, 1 μM, 2.5 μM, 10 μM for HCC827 cells; 25 nM, 100 nM, 1 μM, 2.5 μM, 10 μM for H3255 cells Incubation Time: 24 hours Result: Degradation of both exon-19 deletion EGFR as well as the mutant isoform containing the L858R activating point mutation.
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.

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