Publications by Takahiro Nigawara

Publications by authors named "Takahiro Nigawara"

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Discovery of ASP6918, a KRAS G12C inhibitor: Synthesis and structure-activity relationships of 1-{2,7-diazaspiro[3.5]non-2-yl}prop-2-en-1-one derivatives as covalent inhibitors with good potency and oral activity for the treatment of solid tumors.

Tomoyoshi Imaizumi Itsuro Shimada Yoshiki Satake Susumu Yamaki Takanori Koike Takahiro Nigawara

Bioorg Med Chem

January 2024

Article Synopsis

Recent inhibitors targeting the KRAS G12C mutant protein have shown effectiveness in treating solid tumors, challenging the notion of KRAS as an undruggable target.
A specific compound, 1, was identified as a KRAS G12C inhibitor that works by covalently binding to the protein and demonstrated significant antitumor effects in cell lines and mouse models.
Further modifications to the compound led to the development of ASP6918, which displayed enhanced potency and successfully induced tumor regression in animal studies after oral administration.

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Discovery and biological evaluation of 1-{2,7-diazaspiro[3.5]nonan-2-yl}prop-2-en-1-one derivatives as covalent inhibitors of KRAS G12C with favorable metabolic stability and anti-tumor activity.

Tomoyoshi Imaizumi Michinori Akaiwa Tomoaki Abe Takahiro Nigawara Takanori Koike

Bioorg Med Chem

October 2022

RAS protein plays a key role in cellular proliferation and differentiation. RAS gene mutation is a known driver of oncogenic alternation in human cancer. RAS inhibition is an effective therapeutic treatment for solid tumors, but RAS protein has been classified as an undruggable target.

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