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MedChemExpress - Model Abemaciclib methanesulfonate - 1231930-82-7

Abemaciclib methanesulfonate (LY2835219 methanesulfonate) is a selective CDK4/6 inhibitor with IC50s of 2 nM and 10 nM for CDK4 and CDK6, respectively[1][2][3].

Abemaciclib methanesulfonate

MCE China：Abemaciclib methanesulfonate

Brand：MedChemExpress (MCE)

Cat. No.HY-16297

CAS：1231930-82-7

Synonyms：LY2835219 methanesulfonate

Purity：99.76%

Storage：4°C, sealed storage, away from moisture *In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)

Shipping：Room temperature in continental US; may vary elsewhere.

Description：Abemaciclib methanesulfonate (LY2835219 methanesulfonate) is a selective CDK4/6 inhibitor with IC50s of 2 nM and 10 nM for CDK4 and CDK6, respectively.

In Vitro：Abemaciclib (LY2835219) reduces cell viability with the IC50 values ranging from 0.5 μM to 0.7 μM, inhibits Akt and ERK signaling but not mTOR activation at head and neck squamous cell carcinoma (HNSCC) cells[1]. Abemaciclib (LY2835219) shows inhibition on A375R1-4, M14R, and SH4R with EC50 values ranging from 0.3 to 0.6 μM; Abemaciclib inhibits the proliferation of the parental A375 and resistant A375RV1 and A375RV2 cells with similar potencies with IC50 values of 395, 260, and 463 nM, respectively[2]. Abemaciclib (LY2835219) inhibits CDK4 and CDK6 with low nanomolar potency, inhibits Rb phosphorylation resulting in a G1 arrest and inhibition of proliferation, and its activity is specific for Rb-proficient cells[3].

In Vivo：Abemaciclib (LY2835219) (45 mg/kg, p.o.) in combination with RAD001 causes a cooperative antitumor effect in HNSCC xenograft tumor[1]. Abemaciclib (LY2835219) (45 or 90 mg/kg, p.o.) shows significant tumor growth inhibition in an A375 xenograft model[2].

Animal Administration：Six-week-old BALB/c female nude mice are injected subcutaneously with OSC-19 (1×106) cells. When tumor sizes reach approximately 100 mm3, mice are randomized by tumor size and subjected to each treatment. At least 5 mice per treatment group are included. Each group of mice is dosed via daily oral gavage with vehicle, Abemaciclib (LY2835219) (45 mg/kg/d or 90 mg/kg/d), RAD001 (5 mg/kg/d), or a combination of both. The Abemaciclib (LY2835219) is dissolved in 1% HEC in 20 mM phosphate buffer (pH2.0). Tumor size and body weight are measured twice weekly. Tumor volumes are calculated using the following formula: V=(L × W2)/2 (L, Length; W, width). Mice are gavaged a final time on day 14 and sacrificed the following day. The tumors are removed for Western blot and immunohistochemistry.

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 Abemaciclib (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 antagonistic.

IC50 & Target：Cdk4/cyclin D1 2 nM (IC50) CDK6/cyclinD1 10 nM (IC50) CDK9/cyclinT1 57 nM (IC50) CDK5/p35 287 nM (IC50) Cdk5/p25 355 nM (IC50) CDK2/cyclinE 504 nM (IC50) CDK1/cyclinB1 1627 nM (IC50) CDK7/Mat1/cyclinH1 3910 nM (IC50) PIM1 50 nM (IC50) PIM2 3400 nM (IC50) HIPK2 31 nM (IC50) DYRK2 61 nM (IC50) CK2 117 nM (IC50) GSK3b 192 nM (IC50) JNK3 389 nM (IC50) FLT3 (D835Y) 403 nM (IC50) DRAK1 659 nM (IC50) FLT3 3960 nM (IC50)

References：

[1]. Ku BM, et al. The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma. Oncotarget. 2016 Mar 22;7(12):14803-13. [Content Brief]

[2]. Yadav V, et al. The CDK4/6 inhibitor LY2835219 overcomes PLX4032 resistance resulting from MAPK reactivation and cyclin D1 upregulation. Mol Cancer Ther. 2014 Oct;13(10):2253-63. [Content Brief]

[3]. Gelbert LM, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with NSC 613327. Invest New Drugs. 2014 Oct;32(5):825-37. [Content Brief]

[4]. Wu T, et al. Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42. [Content Brief]

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