Jing Yuan

TL;DR: The discovery of a highly potent (IC50 = 0.071 μM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHp2 in an auto-inhibited conformation demonstrates that pharmacological inhibition of SHP1 is a valid therapeutic approach for the treatment of cancers.

TL;DR: By identifying a drug combination that delays or even combats development of resistance when used as a first-line treatment in clinical trials, these results could ultimately improve the lives of patients with medulloblastoma or other cancers that depend on Smo for their survival.

TL;DR: It is suggested that emergence of F876L may serve as a novel biomarker for prediction of drug sensitivity, predict a "withdrawal" response to MDV3100, and be suitably targeted with other antiandrogens or CDK4/6 inhibitors.

TL;DR: It is shown that overexpression ofAIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal postweaning involution, and the development of malignant mammary tumors, suggesting that an autocrine IGF-I loop underlies the mechanism of AIB1-induced oncogenesis.

TL;DR: Structural-activity relationship studies led to the discovery of a potent and specific Smoothened antagonist N-(6-((2S,6R)-2,6-dimethylmorpholino)pyridin-3-yl)-2-methyl-4'-(trifluoromethoxy)biphenyl- 3-carboxamide (5m, NVP-LDE225), which is currently in clinical development.