Table 1.

Key characteristics of CDK inhibitors

DrugPalbociclib (Pfizer)Ribociclib (Novartis)Abemaciclib (Eli Lilly)
(PD0332991, Ibrance)(LEE011)(LY2835219)
IC50 (in vitro kinase assay, recombinant proteins)CDK4 (D1): 11 nmol/LCDK4: 10 nmol/LCDK4 (D1): 0.6–2 nmol/L
CDK4 (D3): 9 nmol/LCDK6: 39 nmol/LCDK6 (D1): 2.4–5 nmol/L
CDK6 (D2): 15 nmol/LCDK1: >100 μmol/LCDK 9: 57 nmol/L
CDK1: >10 μmol/LCDK2: >50 μmol/LCDK1: >1 μmol/L
CDK2: >10 μmol/L(1, 89)CDK2: >500 nmol/L
(66, 67)(1, 88)
PKTmax 4.2–5.5 hrTmax 4 hrTmax 4–6 h
t1/2 25.9–26.7 hrt1/2 24–36 hrt1/2 17–38 h
(69, 70)(90, 91)(crosses blood:brain barrier; refs. 92, 93)
PDReduced RB phosphorylation in paired tumor biopsies, along with reduced fluorothymidine-PET uptake (75)Reduced RB phosphorylation and Ki67 expression in paired tumor biopsies (90)Reduced RB phosphorylation and topoisomerase IIα expression in paired tumor and skin biopsies (92)
Dosing125 mg daily (3 weeks, 1-week drug holiday) or 200 mg daily (2 weeks, 1-week drug holiday; refs. 69, 70)600 mg daily (3 weeks, 1-week drug holiday; ref. 90)200 mg twice daily (continuous dosing; ref. 92)
Major dose-limitingtoxicitiesNeutropenia, thrombocytopeniaNeutropenia, thrombocytopeniaFatigue
Other reported adverse eventsAnemia, nausea, anorexia, fatigue, diarrhea (69, 70)MucositisDiarrhea
Prolonged EKG QTc intervalNeutropenia (92)
Elevated creatinine
Nausea (90)