Concept of Targeted Drug Conjugate and Its Application in Reversing Drug Resistance DOI
Yuanjiang Wang, Wenqing Xu, Bin Zhang

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Small-molecule targeted drugs have become the mainstream cancer treatment due to their specific therapy. However, drug resistance inevitably happens patients. Herein, we propose "targeted conjugate (TDC)" concept design that enhance antitumor activity, reduce toxicity, and reverse resistance. Upon this idea, compounds Lapa-603 Lapa-604 were obtained by modifying Pt(II) units with Lapatinib's pharmacophore. Research has found can potently inhibit proliferation of tested cells multiple cell targeting EGFR protein causing severe DNA damage. More importantly, presented higher tumor growth inhibitory efficacy than Lapatinib, Cisplatin, or physical mixtures in both MDA-MB-231 BT474 xenograft models. Our research provided promise for development novel based on TDC effectively overcome stronger activity lower toxicity corresponding combination

Language: Английский

Concept of Targeted Drug Conjugate and Its Application in Reversing Drug Resistance DOI
Yuanjiang Wang, Wenqing Xu, Bin Zhang

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Small-molecule targeted drugs have become the mainstream cancer treatment due to their specific therapy. However, drug resistance inevitably happens patients. Herein, we propose "targeted conjugate (TDC)" concept design that enhance antitumor activity, reduce toxicity, and reverse resistance. Upon this idea, compounds Lapa-603 Lapa-604 were obtained by modifying Pt(II) units with Lapatinib's pharmacophore. Research has found can potently inhibit proliferation of tested cells multiple cell targeting EGFR protein causing severe DNA damage. More importantly, presented higher tumor growth inhibitory efficacy than Lapatinib, Cisplatin, or physical mixtures in both MDA-MB-231 BT474 xenograft models. Our research provided promise for development novel based on TDC effectively overcome stronger activity lower toxicity corresponding combination

Language: Английский

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