Trilaciclib hydrochloride (G1T28 hydrochloride) is an inhibitor of CDK4/6 (IC50s: 1 nM and 4 nM for CDK4 and CDK6).

CDK4-CyclinD1:1 nM, CDK6-CyclinD3:4 nM

Incubation with Trilaciclib hydrochloride (G1T28) for 24 hours can induce a strong G1 cell cycle arrest (time=0). Cells have re-entered the cell cycle and demonstrate cell-cycle kinetics similar to untreated control cells By 16 hours after Trilaciclib hydrochloride washout. These results demonstrate that Trilaciclib hydrochloride causes a transient, and reversible G1 arrest. A transient Trilaciclib hydrochloride-mediated G1 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.

G1T28 inhibits the phosphorylation of RB and induces an exclusive, reversible G1 arrest.n vivo, G1T28 reversibly and in a dose-dependent manner, regulates the proliferation of HSPCs.Pretreatment of mice with oral G1T28 allows for the faster recovery of CBCs following chemotherapy treatment.Likewise, oral G1T28 does not protect RB-deficient tumors from chemotherapy but adds to the antitumor effect.Although this effect was found in athymic mice that lack T lymphocytes, it is still possible that the enhanced efficacy is due to preservation of other immune cell types such as natural killer cells.