Table 1.

Biochemical and cellular potencies of selective CDK drugs

AnalysisAbemaciclib LY2835219Palbociclib PD-0332991Ribociclib LEE011Dinaciclib SCH-727965
Biochemical
 CDK1/cyclinA2 Ki (nmol/L)330 ± 90>1,400>1,40018 ± 3
 CDK2/cyclinE1 Ki (nmol/L)150 ± 60>2,500>2,5001.0 ± 0.3
 CDK4/cyclinD3 Ki (nmol/L)0.07 ± 0.010.26 ± 0.030.53 ± 0.084.6 ± 0.6
 CDK5/p35 Ki (nmol/L)86 ± 12>2,000>2,0000.85 ± 0.09
 CDK6/cyclinD1 Ki (nmol/L)0.52 ± 0.170.26 ± 0.072.3 ± 0.31.7 ± 0.2
 CDK7/cyclinH/MAT1 Ki (nmol/L)220 ± 10>2,000>2,00021 ± 2
 CDK9/cyclinT1 Ki (nmol/L)4.1 ± 1.3150 ± 10190 ± 200.13 ± 0.04
PD in cells
 MCF7 IC50 (nmol/L)
  pRb-Ser80713 ± 420 ± 7.589 ± 365.6 ± 0.8
  pRb-Ser7806.1 ± 1.49.3 ± 1.531 ± 8.24.3 ± 0.2
 T47D IC50 (nmol/L)
  pRb-Ser80710 ± 2.921 ± 3.373 ± 1810 ± 2.4
  pRb-Ser7808.9 ± 5.917 ± 1051 ± 3011 ± 10
Cell proliferation
 Breast cancer (MCF-7) IC50 (nmol/L)86 ± 14120 ± 60200 ± 908.7 ± 2.1
 Breast cancer (T47D) IC50 (nmol/L)94 ± 41130 ± 80260 ± 13013 ± 1
 Bone marrow mononuclear cells IC50 (nmol/L)230 ± 27240 ± 431,700 ± 2319 ± 1.3
Cytotoxicity
 Peripheral blood mononuclear cells IC50 (nmol/L)4,700 ± 17518,000 ± 521>10,00011 ± 4.3
 Intestinal epithelial crypt cells (rat) IC50 (nmol/L)930 ± 1874,700 ± 582>10,000<32
 Cardiomyocytes (rat) IC50 (nmol/L)7,200 ± 42013,000 ± 6726,000 ± 59411 ± 3.5
  • NOTE: Biochemical potency is defined as binding affinities (Ki). Phosphorylation of pRb was monitored in two ER+ tumor cell lines to measure pharmacodynamic effects. Surrogate cells from normal tissues were used to assess effects to normal physiology. All values are from at least three independent experiments.