Table 1.
LY2835219 biochemical and cellular profiling
| LY2835219 | |
|---|---|
| Biochemical profilinga | Ki [ATP] (nmol/L) |
| CDK4/cyclinD1 | 0.6 ± 0.3 (n = 2) |
| CDK6/cyclinD1 | 2.4 ± 1.2 (n = 2) |
| IC50 (nmol/L)b | |
| CDK4/cyclinD1 | 2.0 ± 0.4 (n = 5) |
| CDK6/cyclinD1 | 9.9 (n = 1) |
| CDK1/cyclinB1 | 1627 ± 666 (n = 5) |
| CDK2/cyclinE | 504 ± 298 (n = 3) |
| CDK9/cyclinT1 | 57 ± 42 (n = 4) |
| CDK7/Mat1/cyclin H1 | 3910 ± 2410 (n = 4) |
| PIM1 | 50 (n = 1) |
| PIM2 | 3400 (n = 1) |
| bRaf | 6330 (n = 2) |
| Aurora A | >20000 (n = 1) |
| Aurora B | >20000 (n = 1) |
| PLK1 | >20000 (n = 1) |
| PLK3 | >20000 (n = 1) |
| ERK1 | >20000 (n = 1) |
| cRaf | >20000 (n = 2) |
| AKT1 | >20000 (n = 1) |
| HIPK2 | 31 (n = 1)c |
| DYRK2 | 61 (n = 1)c |
| CK2 | 117 (n = 1)c |
| GSK3b | 192 (n = 1) |
| CDK5/p35 | 287 (n = 1)c |
| CDK5/p25 | 355 (n = 1)c |
| JNK3 | 389 (n = 1)c |
| FLT3 (D835Y) | 403 (n = 1)c |
| DRAK1 | 659 (n = 1)c |
| TRKA | 1030 (n = 1)c |
| FLT3 | 3960 (n = 1)c |
| Cellular profiling | IC50 (nmol/L)d |
| pRb inh. (pSer780) colo-205 | 120 ± 36 (n = 6) |
| G1 arrest colo-205 | 72 ± 31 (n = 7, EC50) |
| pRb inh. (pSer780) MDA-MB-361 | 60 ± 40 (n = 3)e |
| G1 arrest MDA-MB-361 | 20 ± 13 (n = 3, EC50)e |
| Cell viability MDA-MB-361 | 90 ± 31 (n = 3)e |
| pCTD inh. (pSer2) U2OS | 3510 ± 1560 (n = 4) |
| pHH1 inh. Calu6 | 17400 ± 4000 (n = 4) |
| pERK inh. HCT116 | >20000 (n = 2) |
| pERK inh. A375 | >20000 (n = 2) |
(a) unless otherwise indicated, all data was generated internally at Eli Lilly and company. All human kinases. (b) for n > 1, average of independent determinations ± standard deviation. (c) IC50 generated at millipore (UBI) kinase panel for kinases >90 % inhibition at 200 nM concentration of inhibitor. (d) geometric mean for n > 1 determinations ± standard deviation. (e) determined after 6 days of incubation due to long doubling times for MDA-MB-361