Palbociclib (PD 0332991) orotate, an orally active selective inhibitor of CDK4 and CDK6, exhibits IC50 values of 11 and 16 nM, respectively. This compound demonstrates potent anti-proliferative effects and induces cell cycle arrest in cancer cells, applicable in research concerning HR-positive, HER2-negative breast cancer, and hepatocellular carcinoma [1] [3] [4].

CDK4-CyclinD3:9 nM, CDK4-CyclinD1:11 nM, CDK6-CyclinD2:16 nM, DYRK1A:2000 nM, MAPK:8000 nM

Palbociclib orotate, at concentrations ranging from 0–1 μM over 24 hours, effectively inhibits Ser 795 phosphorylation in MDA-MB-435 cells, demonstrating an IC50 of 0.063 μM, and similarly impacts Ser 780 and Ser 795 phosphorylation in Colo-205 colon carcinoma cells [1]. At a wider concentration range of 0–10 μM for the same duration, it induces a G1 phase cell cycle arrest in MDA-MB-453 cells [1]. When administered at 500 nM for seven days, palbociclib orotate upregulates homologous gene expression (H2d1, H2k1, and B2m) in both MDA-MB-453 and MDA-MB-361 cells [2]. Additionally, with extended exposure of six days, palbociclib orotate suppresses the growth of various luminal ER-positive and HER2-amplified breast cancer cell lines, with IC50 values spanning from 4 nM to 1 μM [3]. Over a three-day period, it also limits the proliferation of human liver cancer cell lines with IC50 values between 0.01 μM and 3.49 μM and causes reversible cell cycle arrest [4].

Palbociclib orotate, administered orally at doses of 75 or 150 mg/kg daily for 14 days, induces rapid tumor regression and impedes tumor growth [1]. At a dose of 90 mg/kg for 12 days, it also decreases Treg cell quantities and alters the Treg:CD8 ratio in the spleen and lymph nodes of tumor-free mice, highlighting its tumor-independent actions [2]. Furthermore, when given at 100 mg/kg for a week, palbociclib orotate exhibits potent anti-tumor effects in a genetically engineered mosaic mouse model of liver cancer [4].