Article
BBO-10203 inhibits tumor growth without inducing hyperglycemia by blocking RAS-PI3Kα interaction.
Science (New York, N.Y.) - 24 Jul 2025
Simanshu Dhirendra K, Xu Rui, Stice James P, Czyzyk Daniel J, Feng Siyu, Denson John-Paul, Riegler Erin, Yang Yue, Zhang Cathy, Donovan Sofia, Smith Brian P, Abreu-Blanco Maria, Chen Ming, Feng Cindy, Fu Lijuan, Rabara Dana, Young Lucy C, Dyba Marcin, Yan Wupeng, Lin Ken, Ghorbanpoorvalukolaie Samar, Larsen Erik K, Malik Wafa, Champagne Allison, Parker Katie, Ju Jin Hyun, Jeknic Stevan, Esposito Dominic, Turner David M, Lightstone Felice C, Wang Bin, Wehn Paul M, Wang Keshi, Stephen Andrew G, Maciag Anna E, Hata Aaron N, Sinkevicius Kerstin W, Nissley Dwight V, Wallace Eli M, McCormick Frank, Beltran Pedro J
Abstract excerpt
BBO-10203 is an orally available drug that covalently and specifically binds to the rat sarcoma (RAS)-binding domain of phosphoinositide 3-kinase α (PI3Kα), preventing its activation by HRAS, NRAS, and KRAS. It inhibited PI3Kα activation in tumors with oncogenic mutations in KRAS or PIK3CA and in tumors with human epidermal growth factor receptor 2 (HER2) amplification or overexpression. In preclinical models,...
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- Animals
- Female