Multiple Kinase Small Molecule Inhibitor Tinengotinib (TT-00420) Alone or With Chemotherapy Inhibit the Growth of SCLC.

Abstract

There is an urgent need to develop new targeted treatment agents for small cell lung cancer (SCLC). Tinengotinib (TT-00420) is a novel, multi-targeted, and spectrally selective small-molecule kinase inhibitor that has shown significant inhibitory effects on certain solid tumors in preclinical studies. However, its role and mechanism of action in SCLC remain unclear. In this study, we demonstrated that tinengotinib effectively inhibited SCLC cell proliferation, especially highly expressing NeuroD1 (SCLC-N), in the SCLC cell line-derived xenograft (CDX) model and the malignant pleural effusion cell model of patients with SCLC. When combined with etoposide/cisplatin, it synergistically inhibited SCLC growth. Tinengotinib regulates proliferation, apoptosis, migration, cell cycle and angiogenesis in SCLC cells. Mechanistic studies revealed that c-Myc expression may be a key factor influencing the effect of tinengotinib in SCLC-N. This study provides reliable preclinical data and a new direction for tinengotinib as a promising therapy for SCLC, either alone or in combination with chemotherapy.