Drug intelligence / Profile preview

1-105-2

Development stage: Preclinical
Lead developer: Peking University First Hospital
Modality: Small Molecules
Administration: Oral

Overview

1-105-2 is a first-in-class, selective, orally active small molecule inhibitor of phosphorylated TANK-binding kinase 1 (p-TBK1). It is designed to target both cytoplasmic and nuclear p-TBK1 while sparing IKKε. Developed by researchers at Peking University, 1-105-2 exploits synthetic lethality in von Hippel–Lindau (VHL)-deficient clear cell renal cell carcinoma (ccRCC). In preclinical models, 1-105-2 selectively suppresses p-TBK1 (Ser172) and p-P62, restoring apoptosis and demonstrating significant in vivo tumor growth inhibition both as a monotherapy and in combination with anti-PD-1 immunotherapy.

Targets

SQSTM1 (Sequestosome-1)TBK1 (TANK binding kinase 1)

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