| Stereochemistry | ACHIRAL |
| Molecular Formula | C27H32F2N8.CH4O3S |
| Molecular Weight | 602.699 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(O)(=O)=O.CCN1CCN(CC2=CN=C(NC3=NC=C(F)C(=N3)C4=CC5=C(N=C(C)N5C(C)C)C(F)=C4)C=C2)CC1
InChI
InChIKey=NCJPFQPEVDHJAZ-UHFFFAOYSA-N
InChI=1S/C27H32F2N8.CH4O3S/c1-5-35-8-10-36(11-9-35)16-19-6-7-24(30-14-19)33-27-31-15-22(29)25(34-27)20-12-21(28)26-23(13-20)37(17(2)3)18(4)32-26;1-5(2,3)4/h6-7,12-15,17H,5,8-11,16H2,1-4H3,(H,30,31,33,34);1H3,(H,2,3,4)
Abemaciclib, previously known as LY2835219, is a potent and selective inhibitor of cyclin-dependent kinases: CDK4 and CDK6, developed by Eli Lilly, which is in clinical trial phase III for the treatment of breast cancer and non-small cell lung cancer (NSCLC) and in phase II for investigation of its treatment glioblastoma and melanoma.
CNS Activity
Originator
Approval Year
Cmax
AUC
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Sourcing
PubMed
Patents
Sample Use Guides
breast cancer: 150 milligrams (mg) Abemaciclib orally every 12 hours plus either 1 mg anastrozole or 2.5 mg letrozole orally once daily for 28 days (28 day cycles).
non-small cell lung cancer: 200 milligrams (mg) abemaciclib administered, orally, every 12 hours plus best supportive care (BSC) on Days 1 to 28 (28 day cycles).
Route of Administration:
Oral
It was examined the effects of LY2835219 using three head and neck squamous cell carcinoma (HNSCC) cell lines (OSC-19, FaDu, and YD-10B). Cells were treated with LY2835219 at concentrations ranging between 0.01 μM and 10 μM for 72 h. This treatment reduced cell viability at HNSCC cells. The IC50 values for LY2835219 ranged from 0.5 μM to 0.7 μM at HNSCC cells. In addition, LY2835219 inhibited colony formation with long term treatment, indicating that LY2835219 was able to effectively suppress colony formation of HNSCC cells in a dose-dependent manner. OSC-19 cells were treated with 0.1, 0.2, and 0.5 μM LY2835219, and levels of p-AKT (Ser473), p-ERK1/2 (thr202/Tyr204), and p-mTOR (Ser2448) were measured with Western blot analysis. Treatment of cells with LY2835219 inhibited phosphorylation of ERK1/2 and AKT in a dose-dependent manner. Inhibition of AKT by LY2835219 persisted for 48 h after treatment. In contrast, phosphorylation of ERK had recovered at 48 h. Unexpectedly, in spite of inhibition of AKT, LY2835219 had no effect on phosphorylation of mTOR at Ser2448, suggesting continuous activation of mTORC1.
ACTIVE MOIETY
SUBSTANCE RECORD
