Table 2.
Key characteristics of CDK4/6 inhibitors in clinical development for solid tumors.
| Ribociclib (LEE011) (26, 27, 31, 32) | Palbociclib (Ibrance®; PD-0332991) (20, 26, 28) | Abemaciclib (LY2835219) (26, 29, 70) | |
|---|---|---|---|
|
| |||
| IC50 (nM) – on target CDKs | |||
|
| |||
| CDK4–cyclin D1 | 10 | 11 | 2 |
| CDK6–cyclin D1/2/3 | 39 | 16 | 10 |
|
| |||
| IC50 (nM) – on other CDKs | |||
| CDK1–cyclin B | 113,000 | >10,000 | 1627 |
| CDK2–cyclin A/E | 76,000 | >10,000 | 504 |
| CDK5–p25 | 43,900 | >10,000 | 355 |
| CDK9–cyclin T | NR | NR | 57 |
|
| |||
| Kinase partition index | 0.99 | 0.96 | 0.88 |
|
| |||
| Lipophilicity (cLogP) | 2.3 | 2.7 | 5.5 |
|
| |||
| IC50 against bone marrow mononuclear cells (nM) | 1700 ± 231 | 240 ± 43 | 230 ± 27 |
|
| |||
| Half-life | 33–42 hours | 26–27 hours | 17–38 hours |
|
| |||
| Tmax | 1–5 hours | 6–12 hours | 4–6 hours |
cLogP, calculated Log of the partition coefficient.