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Article

Design of Orally-bioavailable Tetra-cyclic phthalazine SOS1 inhibitors with high selectivity against EGFR.

Bioorganic chemistry - 1 Jul 2023

He Huan, Chen Ruiqi, Wang Ziwei, Qing Luolong, Zhang Yu, Liu Yi, Pan Weidong, Fang Huaxiang, Zhang Silong

Abstract excerpt

KRAS mutations (G12C, G12D, etc.) are implicated in the oncogenesis and progression of many deadliest cancers. Son of sevenless homolog 1 (SOS1) is a crucial regulator of KRAS to modulate KRAS from inactive to active states. We previously discovered tetra-cyclic quinazolines as an improved scaffold for inhibiting SOS1-KRAS interaction. In this work, we report the design of tetra-cyclic phthalazine derivatives for...

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PMID: 37054529
DOI: 10.1016/j.bioorg.2023.106536

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