PROTAC EGFR degrader 3

• CAT Number: I043883
• CAS Number: 2768472-28-0
• Molecular Formula: C60H77N13O5S
• Molecular Weight: 1092.40
• Purity: ≥95%
• Synonyms: (2S,4R)-1-[(2S)-2-[8-[4-[4-[[8-anilino-9-[(3S)-1-prop-2-enoylpiperidin-3-yl]purin-2-yl]amino]phenyl]piperazin-1-yl]octanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
• InChI: InChI=1S/C60H77N13O5S/c1-7-52(76)71-30-16-19-47(37-71)73-55-49(66-59(73)65-44-17-12-11-13-18-44)36-61-58(68-55)64-45-25-27-46(28-26-45)70-33-31-69(32-34-70)29-15-10-8-9-14-20-51(75)67-54(60(4,5)6)57(78)72-38-48(74)35-50(72)56(77)63-40(2)42-21-23-43(24-22-42)53-41(3)62-39-79-53/h7,11-13,17-18,21-28,36,39-40,47-48,50,54,74H,1,8-10,14-16,19-20,29-35,37-38H2,2-6H3,(H,63,77)(H,65,66)(H,67,75)(H,61,64,68)/t40-,47-,48+,50-,54+/m0/s1
• InChIKey: RYXQXEGTLNBKEC-DKQRTKIFSA-N
• SMILES: CC1=C(SC=N1)C2=CC=C(C=C2)C(C)NC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)CCCCCCCN4CCN(CC4)C5=CC=C(C=C5)NC6=NC=C7C(=N6)N(C(=N7)NC8=CC=CC=C8)C9CCCN(C9)C(=O)C=C)O

PROTAC EGFR degrader 3 is a potent PROTAC EGFR degrader. PROTAC EGFR degrader 3 shows excellent cellular activity against the H1975 and HCC827 cells with high selectively. PROTAC EGFR degrader 3 shows that the lysosome is involved in the degradation process of EGFR mutant degradation[1].
PROTAC EGFR degrader 3 (compound CP17) shows anti-proliferative activity of PROTACs with IC50s of 32 nM, 1.60 nM, >10000nM for H1975 (EGFRL858/T790M), HCC827 (EGFRdel19), A431 (EGFRWT) cells, respectively[1].
PROTAC EGFR degrader 3 (0, 10, 100, 1000, 10000 nM) exhibits poor cellular activity with IC50 of 481 nM, 669 nM for Ba/F3 (EGFRdel19/T790M/C797S) and Ba/F3 (EGFRL858/T790M/C797S) cells, respectively[1].
PROTAC EGFR degrader 3 (0-10000 nM) suppresses the proliferation of the PC9 (EGFRdel19/T790M/C797S) and H1975 (EGFRL858/T790M/C797S) cells, respectively[1].
PROTAC EGFR degrader 3 (30 nM; 0-72 h) decreases the expression level of EGFRL858/T790M after 8h, and degradation rate maximizes after 48 h[1].
PROTAC EGFR degrader 3 (0.3, 1, 3, 10, 100, 300 nM; 24, 48 h) induces the degradation of EGFRL858/T790M and EGFRdel19 with DC50s of 1.56 nM and 0.49 nM, respectively[1].
PROTAC EGFR degrader 3 (100, 1000 nM; 24 h) shows selective against mutant EGFR in the H1975 and HCC827 cells[1].
PROTAC EGFR degrader 3 (0.3, 1, 3, 10, 100, 300 nM; 24 h) effectively blocks EGFR singnal transduction, leading to cell proliferation inhibition[1].
PROTAC EGFR degrader 3 (30 nM) induces EGFR mutant degradation, and the lysosome is involved in the degradation process[1].

Reference

[1]. Zhao HY, et al. Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands. J Med Chem. 2022; 65(6):4709-4726.
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