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Details

Stereochemistry ACHIRAL
Molecular Formula C27H32F2N8
Molecular Weight 506.5934
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ABEMACICLIB

SMILES

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=UZWDCWONPYILKI-UHFFFAOYSA-N
InChI=1S/C27H32F2N8/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/h6-7,12-15,17H,5,8-11,16H2,1-4H3,(H,30,31,33,34)

HIDE SMILES / InChI

Molecular Formula C27H32F2N8
Molecular Weight 506.5934
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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.
Substance Class Chemical
Created
by admin
on Tue Mar 06 10:53:44 UTC 2018
Edited
by admin
on Tue Mar 06 10:53:44 UTC 2018
Record UNII
60UAB198HK
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ABEMACICLIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
VERZENIO
Brand Name English
ABEMACICLIB [WHO-DD]
Common Name English
LY2835219
Code English
2-PYRIMIDINAMINE, N-(5-((4-ETHYL-1-PIPERAZINYL)METHYL)-2-PYRIDINYL)-5-FLUORO-4-(4-FLUORO-2-METHYL-1-(1-METHYLETHYL)-1H-BENZIMIDAZOL-6-YL)
Systematic Name English
LY-2835219
Code English
ABEMACICLIB [INN]
Common Name English
ABEMACICLIB [USAN]
Common Name English
Code System Code Type Description
NCI_THESAURUS
C97660
Created by admin on Tue Mar 06 10:53:44 UTC 2018 , Edited by admin on Tue Mar 06 10:53:44 UTC 2018
PRIMARY
ChEMBL
CHEMBL3301610
Created by admin on Tue Mar 06 10:53:44 UTC 2018 , Edited by admin on Tue Mar 06 10:53:44 UTC 2018
PRIMARY
INN
10036
Created by admin on Tue Mar 06 10:53:44 UTC 2018 , Edited by admin on Tue Mar 06 10:53:44 UTC 2018
PRIMARY
EPA CompTox
1231929-97-7
Created by admin on Tue Mar 06 10:53:44 UTC 2018 , Edited by admin on Tue Mar 06 10:53:44 UTC 2018
PRIMARY
CAS
1231929-97-7
Created by admin on Tue Mar 06 10:53:44 UTC 2018 , Edited by admin on Tue Mar 06 10:53:44 UTC 2018
PRIMARY
EVMPD
SUB171907
Created by admin on Tue Mar 06 10:53:44 UTC 2018 , Edited by admin on Tue Mar 06 10:53:44 UTC 2018
PRIMARY
PUBCHEM
46220502
Created by admin on Tue Mar 06 10:53:44 UTC 2018 , Edited by admin on Tue Mar 06 10:53:44 UTC 2018
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
BINDER -> LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC