Novel Cyclic Peptide–Drug Conjugate P6-SN38 Toward Targeted Treatment of EGFR Overexpressed Non-Small Cell Lung Cancer

Andrii Bazylevich, Ayala Miller, Iryna Tkachenko, Maia Merlani, Leonid Patsenker, Gary Gellerman, Bat Chen R. Lubin

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

Background/Objectives: Here, we report on the synthesis and biological evaluation of a novel peptide–drug conjugate, P6-SN38, which consists of the EGFR-specific short cyclic peptide, P6, and the Topo I inhibitor SN38, which is a bioactive metabolite of the anticancer drug irinotecan. Methods: SN38 is attached to the peptide at position 20 of the E ring’s tertiary hydroxyl group via a mono-succinate linker. Results: The developed peptide–drug conjugate (PDC) exhibited sub-micromolar anticancer activity on EGFR-positive (EGFR+) cell lines but no effect on EGFR-negative (EGFR−) cells. In vivo studies have shown that this PDC specifically accumulates in EGFR+ non-small cell lung cancer (NSCLC) xenografts and presents superior anticancer activity compared to the EGFR-specific antibody cetuximab (ErbituxTM) and free SN38. The 10 mg/kg dose of P6-SN38 in a side-by-side EGFR+/EGFR− xenograft shows eradication of the EGFR+ tumor with good tolerance, but no inhibition of tumor growth of the EGFR− counterpart. Conclusions: The PDC examined in this study was proven to be highly efficient for NSCLC, broadening its utilization for targeted cancer therapy in EGFR overexpressed cancers.

اللغة الأصليةالإنجليزيّة
رقم المقال1613
دوريةPharmaceutics
مستوى الصوت16
رقم الإصدار12
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - ديسمبر 2024

بصمة

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