Abemaciclib

Alias: Abemaciclib; LY2835219; LY-2835219; LY 2835219; Abemaciclib methanesulfonate; LY2835219 methanesulfonate

Cat No.:V3692 Purity: ≥98%

COA Product Data Instructions for use SDS

Abemaciclib Chemical Structure CAS No.: 1231929-97-7
Product category: CDK

This product is for research use only, not for human use. We do not sell to patients.

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Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

InvivoChem's 阿贝西利 has been cited by 1 publication

[1] Acta Neuropathol. 2023 Jul;146(1):145-162.

Purity & Quality Control Documentation

Current batch：

Purity: =99.6%

COA

MSDS

NMR

LC-MS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Abemaciclib (formerly known as LY2835219; trade name: Verzenio) is a potent and selective, and orally bioavailable dual inhibitor of CDK4 (cyclin-dependent kinase) and CDK6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively. Abemaciclib received FDA approval in September 2017 to treat specific advanced or metastatic breast cancers. Early G1 retinoblastoma (Rb) protein phosphorylation is inhibited by LY2835219, which specifically inhibits CDK4 and 6. By stopping CDK-mediated G1-S phase transition, inhibition of Rb phosphorylation stops the cell cycle in the G1 phase, inhibiting DNA synthesis and slowing the growth of cancer cells. As observed in some cancer forms, overexpression of the serine/threonine kinases CDK4/6 can result in cell cycle dysregulation.

Biological Activity I Assay Protocols (From Reference)

Targets

Cdk4/cyclin D1 (IC50 = 2 nM); CDK6/cyclinD1 (IC50 = 10 nM); CDK9/cyclinT1 (IC50 = 57 nM); CDK5/p35 (IC50 = 287 nM); Cdk5/p25 (IC50 = 355 nM); CDK2/cyclinE (IC50 = 504 nM); CDK7/Mat1/cyclinH1 (IC50 = 3910 nM); CDK1/cyclinB1 (IC50 = 1627 nM); PIM1 (IC50 = 39 nM); PIM2 (IC50 = 3400 nM); HIPK2 (IC50 = 31 nM); DYRK2 (IC50 = 61 nM); CK2 (IC50 = 117 nM); GSK3b (IC50 = 192 nM); JNK3 (IC50 = 389 nM); FLT3 (D835Y) (IC50 = 403 nM); FLT3 (IC50 = 3960 nM); DRAK1 (IC50 = 659 nM)

ln 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 manufacturers 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 manufacturers 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.

ln Vivo

Abemaciclib exhibits both single-agent antitumor activity and durable cell-cycle inhibition in a colorectal cancer xenograft model that was used to create an integrated pharmacokinetic/pharmacodynamic model. Abemaciclib can be dosed orally on a continuous schedule to achieve sustained target inhibition. Numerous other human cancer xenograft models, such as those derived from melanoma, glioblastoma, mantle cell lymphoma, and non-small cell lung cancer (NSCLC), show tumor growth inhibition. In an intracranial glioblastoma xenograft model, bemaciclib diffuses across the blood–brain barrier and increases survival time. Abemaciclib's pharmacokinetics in humans indicate a slow absorption phase, with a median of 4 to 6 hours between the oral dose and the maximum plasma concentration (tmax). It is distributed and cleared thoroughly. The average terminal elimination half-life (t1/2) varied between 17.4 and 38.1 hours, and there was no discernible shift in clearance that was dose-dependent[2].

Cell Assay

The 96-well plate is seeded with cells, which are then left to adhere for an entire night before being treated for 72 hours with either the indicated compounds or DMSO control (0.1% v/v). A Cell Counting Kit is used, as directed by the manufacturer, to assess the viability and proliferation of cells. CompuSyn is used to analyze the relationship between mTOR inhibitor and Abemaciclib. An additive drug interaction is indicated by a combination index (CI) value of 1, while a synergistic or antagonistic drug interaction is indicated by a CI value of <1 or >1.

Animal Protocol

Dissolved in 1% HEC in 20 mM phosphate buffer (pH2.0); 45 mg/kg/d or 90 mg/kg/d)

Subcutaneous injections of OSC-19 (1×10⁶) cells are given to six-week-old BALB/c female nude mice. Mice are randomized by tumor size and given each treatment when tumor sizes approach 100 mm³. Each treatment group comprises a minimum of 5 mice. Every group of mice receives a daily oral gavage dose of either RAD001 (5 mg/kg/d), Abemaciclib (45 mg/kg/d or 90 mg/kg/d), or a combination of both. In 20 mM phosphate buffer (pH 2.0), 1% HEC is used to dissolve the Abemaciclib. Weight and tumor size are measured twice a week. V=(L×W²)/2 is the formula used to compute tumor volumes. On day 14, mice undergo one last gavage before being sacrificed the next day. In order to perform immunohistochemistry and Western blot, the tumors are removed.

References

[1]. Drug Des Devel Ther . 2018 Feb 16:12:321-330.

[2]. Cancer Discov . 2016 Jul;6(7):740-53.

[3]. Cell Rep . 2018 Mar 13;22(11):2978-2994.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C27H32F2N8

Molecular Weight

506.59

Exact Mass

506.27

Elemental Analysis

C, 64.01; H, 6.37; F, 7.50; N, 22.12

CAS #

1231929-97-7

Related CAS #

Abemaciclib methanesulfonate;1231930-82-7;Abemaciclib-d8;2088650-53-5

Appearance

White to off-white solid powder

SMILES

CCN1CCN(CC1)CC2=CN=C(C=C2)NC3=NC=C(C(=N3)C4=CC5=C(C(=C4)F)N=C(N5C(C)C)C)F

InChi Key

UZWDCWONPYILKI-UHFFFAOYSA-N

InChi Code

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)

Chemical Name

N-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-amine

Synonyms

Abemaciclib; LY2835219; LY-2835219; LY 2835219; Abemaciclib methanesulfonate; LY2835219 methanesulfonate

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: >10 mM

Water: N/A

Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: 3.33 mg/mL (6.57 mM) in 0.5% HEC (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.

Solubility in Formulation 2: 5% DMSO+40% PEG 300+5%Tween80+ 50%ddH2O: 0.2mg/ml

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9740 mL	9.8699 mL	19.7398 mL
	5 mM	0.3948 mL	1.9740 mL	3.9480 mL
	10 mM	0.1974 mL	0.9870 mL	1.9740 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

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The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

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The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
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In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03905889	Active Recruiting	Drug: Abemaciclib Drug: Sunitinib	Renal Cell Carcinoma Metastatic	Brown University	June 5, 2019	Phase 1
NCT04227327	Active Recruiting	Drug: Abemaciclib Drug: Aromatase Inhibitors	Advanced Breast Cancer	University of Milano Bicocca	January 7, 2020	Phase 2
NCT04074785	Active Recruiting	Drug: Abemaciclib Drug: Bevacizumab	GBM Glioblastoma	University of Texas Southwestern Medical Center	December 13, 2019	Early Phase 1
NCT03339843	Active Recruiting	Drug: Abemaciclib	Esophagus SCC Cholangiocarcinoma	Jules Bordet Institute	December 19, 2018	Phase 2
NCT04552769	Active Recruiting	Drug: Abemaciclib	Thyroid Cancer Anaplastic Thyroid Cancer	Stanford University	September 10, 2020	Phase 2

Biological Data

Effects of LY2835219 on RB pathway and intracellular signaling.Oncotarget.2016 Mar 22;7(12):14803-13.
Combined effect of LY2835219 and mTOR inhibitorsin vitro.Oncotarget.2016 Mar 22;7(12):14803-13.
LY2835219 and mTOR inhibitor combination in HNSCC xenograft tumor model.Oncotarget.2016 Mar 22;7(12):14803-13.
Antitumor activity of LY2835219 in HNSCC xenograft tumor model.Oncotarget.2016 Mar 22;7(12):14803-13.
Effects of CDK4/6 inhibitor LY2835219 on cell growth in HNSCC.Oncotarget.2016 Mar 22;7(12):14803-13.
Effects of LY2835219 on cell proliferation and cell cycle in HNSCC.Oncotarget.2016 Mar 22;7(12):14803-13.