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
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)
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 |
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
Title | Date | PubMed |
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The landscape of somatic copy-number alteration across human cancers. | 2010 Feb 18 |
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A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma. | 2010 Jul 13 |
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Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors. | 2012 Jul 15 |
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Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia. | 2012 Oct 16 |
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The requirement for cyclin D function in tumor maintenance. | 2012 Oct 16 |
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A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS. | 2013 Jul |
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Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. | 2014 Oct |
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.
Substance Class |
Chemical
Created
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admin
on
Edited
Mon Oct 21 21:26:27 UTC 2019
by
admin
on
Mon Oct 21 21:26:27 UTC 2019
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Record UNII |
60UAB198HK
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C129825
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NDF-RT |
N0000175605
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NCI_THESAURUS |
C2185
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WHO-ATC |
L01XE50
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C97660
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CHEMBL3301610
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10036
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1231929-97-7
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1231929-97-7
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SUB171907
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46220502
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
IC50
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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TARGET->WEAK INHIBITOR |
IC50
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TARGET -> INHIBITOR |
IC50
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TRANSPORTER -> INHIBITOR |
IC50
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TRANSPORTER -> SUBSTRATE | |||
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EXCRETED UNCHANGED |
AMOUNT EXCRETED
FECAL
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TRANSPORTER -> INHIBITOR |
IC50
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TARGET -> INHIBITOR |
IC50
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TRANSPORTER -> SUBSTRATE | |||
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SALT/SOLVATE -> PARENT | |||
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BINDER->LIGAND |
BINDING
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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blood-to-plasma ration | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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