Méthanesulfonate d'abémaciclib (méthanesulfonate LY2835219) est un inhibiteur sélectif de CDK4 / 6 avec des IC50s de 2 nM et 10 nM pour CDK4 et CDK6, respectivement.
Abemaciclib-Methansulfonat (LY2835219-Methansulfonat) ist ein selektiver CDK4/6-Inhibitor mit IC50-Werten von 2 nM und 10 nM für CDK4 bzw. CDK6.
Abemaciclib methanesulfonate (LY2835219 methanesulfonate) is a selective CDK4/6 inhibitor with IC50s of 2 nM and 10 nM for CDK4 and CDK6, respectively.
For research use only. We do not sell to patients.
Abemaciclib methanesulfonate Chemical Structure
CAS No. : 1231930-82-7
Based on 86 publication(s) in Google Scholar
Other Forms of Abemaciclib methanesulfonate:
Abemaciclib
In-stock
Abemaciclib methanesulfonate purchased from MedChemExpress. Usage Cited in:
Nature. 2017 Aug 24;548(7668):471-475.
[Abstract]
Western blot of SKBR3, BT474, MDA-MB-453, and MDA-MB-361 cells treated with DMSO, GW572016, or Abemaciclib for 48 h.
Western blot of MDA-MB-453 cells pretreated with DMSO or Abemaciclib (500 nM) for 0, 1, or 7 days before exposure to Staurosporine (500 nM) for 4 h.
Abemaciclib methanesulfonate purchased from MedChemExpress. Usage Cited in:
Cancer Res. 2017 May 1;77(9):2488-2499.
[Abstract]
Treatment with PD 0332991 and Abemaciclib shows an induction of S241 P-PDK1 as early as 1 h after drug exposure without an increased in total PDK1 protein.
Effects of CDK4/6 inhibitors on AMPK phosphorylation and apoptosis-related signals. After 24 h of drug treatment, the cells are subjected to western blot analysis. AMPK phosphorylation level is quantified by the ratio of band intensities of phospho-AMPKα vs. AMPKα.
Abemaciclib methanesulfonate purchased from MedChemExpress. Usage Cited in:
Biochem Pharmacol. 2017 Jan 15;124:29-42.
[Abstract]
Effect of LY2835219 on the expression of ABCB1 or ABCG2 in MDR cells. The protein level of ABCB1 and ABCG2 on MDR cells after 0, 0.1, 0.2 and 0.4 μM LY2835219 stimulation for 48h are measured by Western blot analysis, and mRNA level are measured by PCR (GAPDH as loading control).
Abemaciclib methanesulfonate purchased from MedChemExpress. Usage Cited in:
Oncotarget. 2017 Jun 27;8(40):67422-67438.
[Abstract]
GTSE1 protein and mRNA levels in MDA-MB-157 and MDA-MB-231 cell lines treated respectively with Abemaciclib 0.5 μM for 24h. Data are presented as mean±SEM of three independent experiments.
Abemaciclib causes increased PARP cleavage in RCC. In 786-O cells Abemaciclib exposure results in increased PARP cleavage. This effect is more rapid and pronounced when Abemaciclib is combined with SU 11248.
Abemaciclib causes increased PARP cleavage in RCC. In Caki-1 cells Abemaciclib exposure results in increased PARP cleavage. This effect is more rapid and pronounced when Abemaciclib is combined with SU 11248.
Abemaciclib methanesulfonate purchased from MedChemExpress. Usage Cited in:
Cancer Res. 2016 Nov 15;76(22):6723-6734.
[Abstract]
The effects of the CDK inhibitor Abemaciclib, PD 0332991 and Ribocilib on Trop2 ICD cleavage. CDK inhibitors decrease Trop2 ICD abundance after the 2nd day of CDK inhibitor treatment.
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].
IC50 & Target[3]
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)
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Abemaciclib methanesulfonate Related Antibodies
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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
*In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)
Solvent & Solubility
In Vitro:
H2O : 125 mg/mL (207.40 mM; Need ultrasonic)
DMSO : 10 mg/mL (16.59 mM; ultrasonic and warming and heat to 80°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
1.6592 mL
8.2960 mL
16.5920 mL
5 mM
0.3318 mL
1.6592 mL
3.3184 mL
10 mM
0.1659 mL
0.8296 mL
1.6592 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
*
Note: If you choose water as the stock solution, please dilute it to the working solution,
then filter and sterilize it with a 0.22 μm filter before use.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.15 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (4.15 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3
Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (4.15 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (25.0 mg/mL) to 900 μLCorn oil, and mix evenly.
Protocol 4
Add each solvent one by one: 5% DMSO 40% PEG300 5% Tween-80 50% Saline
Solubility: 2 mg/mL (3.32 mM); Suspended solution; Need ultrasonic
Protocol 5
Add each solvent one by one: 5% DMSO 95% (20% SBE-β-CD in Saline)
Solubility: ≥ 2 mg/mL (3.32 mM); Clear solution
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution.
If precipitation or phase separation occurs during preparation,
heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: PBS
Solubility: 25 mg/mL (41.48 mM); Clear solution; Need ultrasonic
Protocol 2
Add each solvent one by one: 0.5% Hydroxyethyl cellulose in Water
Solubility: 12.5 mg/mL (20.74 mM); Clear solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration:
mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).
[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]
Cell Assay
[1]
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 synergistic and a CI of > 1 is antagonistic.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]
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.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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]
[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.
[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.
[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.
[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.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture). When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO / H2O
1 mM
1.6592 mL
8.2960 mL
16.5920 mL
41.4800 mL
5 mM
0.3318 mL
1.6592 mL
3.3184 mL
8.2960 mL
10 mM
0.1659 mL
0.8296 mL
1.6592 mL
4.1480 mL
15 mM
0.1106 mL
0.5531 mL
1.1061 mL
2.7653 mL
H2O
20 mM
0.0830 mL
0.4148 mL
0.8296 mL
2.0740 mL
25 mM
0.0664 mL
0.3318 mL
0.6637 mL
1.6592 mL
30 mM
0.0553 mL
0.2765 mL
0.5531 mL
1.3827 mL
40 mM
0.0415 mL
0.2074 mL
0.4148 mL
1.0370 mL
50 mM
0.0332 mL
0.1659 mL
0.3318 mL
0.8296 mL
60 mM
0.0277 mL
0.1383 mL
0.2765 mL
0.6913 mL
80 mM
0.0207 mL
0.1037 mL
0.2074 mL
0.5185 mL
100 mM
0.0166 mL
0.0830 mL
0.1659 mL
0.4148 mL
*
Note: If you choose water as the stock solution, please dilute it to the working solution,
then filter and sterilize it with a 0.22 μm filter before use.
Abemaciclib methanesulfonate Related Classifications
Cell Cycle/DNA Damage
CDK
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.