CAS NO: | 1231930-82-7 |
规格: | ≥98% |
包装 | 价格(元) |
25mg | 电议 |
50mg | 电议 |
100mg | 电议 |
250mg | 电议 |
500mg | 电议 |
1g | 电议 |
Molecular Weight (MW) | 602.7 |
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Formula | C27H32F2N8.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 |
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. |
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In Vivo | LY2835219 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 model | BALB/c female nude mice are injected subcutaneously with OSC-19 (1×106) cells |
Formulation & Dosage | Dissolved in 1% HEC in 20 mM phosphate buffer (pH2.0); 45 mg/kg/d or 90 mg/kg/d) |
References | Oncotarget. 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. |