曲拉西利

Incubation with Trilaciclib (G1T28) for 24 hours induces a robust G ₁ cell-cycle arrest (time=0). By 16 hours after Trilaciclib hydrochloride washout, cells have reentered the cell cycle and demonstrate cell-cycle kinetics similar to untreated control cells. These results demonstrate that Trilaciclib causes a transient, and reversible G ₁ arrest. A transient Trilaciclib-mediated G ₁ cell-cycle arrest in CDK4/6-sensitive cells decreases the in vitro toxicity of a variety of commonly used cytotoxic chemotherapy agents associated with myelosuppression.

Trilaciclib (G1T28) treatment results in a robust and dose-dependent suppression of proliferation in HSPCs at 12 hours, with EdU incorporation returning near baseline levels in a dose-dependent manner by 24 hours after administration. These data demonstrate that a single oral dose of Trilaciclib can produce reversible cell-cycle arrest in HSPCs in a dose-dependent manner in vivo . Mice given 100 mg/kg Trilaciclib 30 minutes prior to etoposide treatment, exhibits only background levels of caspase-3/7 activity. These data demonstrate that Trilaciclib can protect the bone marrow from chemotherapy-induced apoptosis in vivo . The data demonstrate that treatment with Trilaciclib prior to 5-FU likely decreases 5-FU-induced damage by chemotherapy in HSPCs, thus accelerating blood count recovery after chemotherapy.