TUBG1 inhibitor L12 is a specific inhibitor of γ-tubulin1 (TUBG1) and γ-tubule polymerizing agent, selectively inhibits TUBG1 activity in RB1-deficient tumor cells without affecting TUBG2.
L12 exhibits heightened toxicity in cells lacking RB1 expression (human retinoblastoma Y79, small cell lung carcinoma U1690 cells), as well as in cells with a constitutively phosphorylated RB1 (human osteosarcoma U2OS cells lacking expression of p16INK,55 leading to constitutive phosphorylation of RB1, with IC50 of 30.13 nM.
L12 selectively targets cancer cells with an impaired RB1 pathway or associated mechanisms, interferes with the activities of the TUBG–E2F1–RB1 network.
L12 increased the number of cells with γ-tubules.
L12 demonstrates less neuronal axonal toxicity compared to vincristine treatment on neuronal axons.
L12 (10 mg/kg) delays xenograft tumor growth in tumor cells with an impaired RB1 pathway in  xenografted U1690 mice.