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Abemaciclib(LY2835219)mesylate
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Abemaciclib(LY2835219)mesylate图片
CAS NO:1231930-82-7
规格:≥98%
包装与价格:
包装价格(元)
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议
1g电议

产品介绍
Abemaciclib mesylate (formerly known as LY-2835219; LY2835219; trade name: Verzenio) is a potent and selective, orally bioavailable dual inhibitor of CDK4 (cyclin-dependent kinase) and CDK6 with potential antineoplastic activity. It inhibits CDK4/6 with IC50s of 2 nM and 10 nM in cell-free assays, respectively. In September 2017, Abemaciclib was approved by FDA to treat certain advanced or metastatic breast cancers. LY2835219 acts by specifically inhibiting CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation in early G1. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of the serine/threonine kinases CDK4/6 can cause cell cycle deregulation as seen in certain types of cancer.
理化性质和储存条件
Molecular Weight (MW)602.7
FormulaC27H32F2N8.CH4O3S
CAS No.1231930-82-7 (mesylate);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 83 mg/mL (137.7 mM)
Water: 100 mg/mL (165.9 mM)
Ethanol: 24 mg/mL (39.8 mM)
Solubility (In vivo)Water: 100 mg/mL (165.9 mM)
Synonyms

Abemaciclib; LY-2835219 mesylate; LY2835219; LY 2835219; Abemaciclib mesylate;

Chemical Name: N-(5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine mesylate

SMILES Code: CC1=NC2=C(F)C=C(C3=NC(NC4=NC=C(CN5CCN(CC)CC5)C=C4)=NC=C3F)C=C2N1C(C)C.OS(=O)(C)=O

Exact Mass: 602.2599

实验参考方法
In Vitro

In vitro activity: Abemaciclib (formerly known as LY2835219) is a potent and selective, orally available dual inhibitor of CDK4 (cyclin-dependent kinase) and CDK6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively. LY2835219 specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation in early G1. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of the serine/threonine kinases CDK4/6 can cause cell cycle deregulation as seen in certain types of cancer.


Kinase Assay: Cells (5 × 103) are plated in 96 well plates. Cells are treated the next day for 24 to 48 hours and then assessed for caspase-3 activity by Caspase-Glo-3/7 Assay, as per manufacturer's instructions and a luminescence plate reader.


Cell Assay: Cells are seeded in a 96-well plate, allowed to adhere overnight, and treated with DMSO control (0.1% v/v) or the indicated compounds for 72 h. Cell viability and proliferation are determined using a Cell Counting Kit according to the manufacturer's instructions. The interaction between LY2835219 and mTOR inhibitor is determined using CompuSyn. Combination index (CI) values of 1 indicates and additive drug interaction, whereas a CI of < 1 is synergistic and a CI of> 1 is antagonistic.

In VivoLY2835219 saturates BBB efflux with an unbound plasma IC50 of about 95 nM. The percent of dose in brain for LY2835219-MsOH is 0.5–3.9%. In both a subcutaneous and intracranial human glioblastoma model (U87MG), LY2835219-MsOH suppressed tumor growth in a dose-dependent manner both as a single agent, and in combination with temozolomide.
Animal modelBALB/c female nude mice are injected subcutaneously with OSC-19 (1×106) cells
Formulation & DosageDissolved in 1% HEC in 20 mM phosphate buffer (pH2.0); 45 mg/kg/d or 90 mg/kg/d)
ReferencesOncotarget. 2016 Mar 22;7(12):14803-13; Biochem Pharmacol. 2017 Jan 15;124:29-42; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract B234.