Abemaciclib

Catalog No.S5716 Batch:S571602

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Technical Data

Formula

C27H32F2N8
Molecular Weight 506.59 CAS No. 1231929-97-7
Solubility (25°C)* In vitro DMSO 10 mg/mL (19.73 mM)
Ethanol 6 mg/mL (11.84 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Abemaciclib is a cell cycle inhibitor selective for CDK4/6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively.
Targets
CDK4 [1]
(Cell-free assay)		 CDK6 [1]
(Cell-free assay)
2 nM 10 nM
In vitro Abemaciclib highly selective inhibits the complexes CDK4/ cyclin D1 (IC50 =2 nmol/L) and CDK6/cyclin D1 (IC50 =10 nmol/L), with no activity against other CDK/cyclin complexes or cell-cycle-related kinases within the nanomolar ranges, except for inhibition of CDK9 at IC50 at least five times higher. Besides the cell-cycle dependent activity, abemaciclib is able to boost antitumor immunity by potentiating tumor antigen presentation and selectively suppressing proliferation of regulatory T (Treg) cells at the same time[1]. Consistent with its activity against CDK4 and CDK6, abemaciclib inhibits RB phosphorylation and leads to G1 arrest in RB-proficient cell lines[2]. In vitro, treatment with abemaciclib resulted in increased activation of human T cells and upregulated expression of antigen presentation genes in MCF-7 breast cancer cells[3].
In vivo In a colorectal cancer xenograft model used to develop an integrated pharmacokinetic/pharmacodynamic model, abemaciclib can be dosed orally on a continuous schedule to achieve sustained target inhibition and demonstrates not only durable cell-cycle inhibition but also single-agent antitumor activity. Tumor growth inhibition is observed in multiple other human cancer xenograft models, including those derived from non-small cell lung cancer (NSCLC), melanoma, glioblastoma, and mantle cell lymphoma. Abemaciclib distributes across the blood–brain barrier and prolongs survival in an intracranial glioblastoma xenograft model. In human, The pharmacokinetics of abemaciclib shows a slow absorption phase with a median time from oral dose to maximum plasma concentration (tmax) ranging from 4 to 6 hours. It is extensively cleared and distributed. The mean terminal elimination half-life (t1/2) ranged from 17.4 to 38.1 hours with no apparent dose-dependent change in clearance[2].

Protocol (from reference)

Cell Assay:

[3]
  • Cell lines

    CT26 tumor cell line

  • Concentrations

    0-10 μM

  • Incubation Time

    96 h

  • Method

    Tumor cells were cultured for 4 hr alone at 37°C, and then abemaciclib, palbociclib, or DMSO control was added at indicated concentrations for 96 hr at 37°C. Cell viability was then assessed.
Animal Study:

[2]
  • Animal Models

    Athymic nude mice implanted with human NSCLC xenograft tumors

  • Dosages

    25, 50, or 100 mg/kg/d

  • Administration

    oral

Selleck's Abemaciclib has been cited by 112 publications

GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant [ Cancer Cell, 2024, S1535-6108(24)00305-2] PubMed: 39232581
Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment [ Cancer Cell, 2024, S1535-6108(24)00037-0] PubMed: 38402610
Integrative clinical and preclinical studies identify FerroTerminator1 as a potent therapeutic drug for MASH [ Cell Metab, 2024, S1550-4131(24)00284-5] PubMed: 39142286
EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in desmoplastic small round cell tumors [ Nat Commun, 2024, 15(1):7460] PubMed: 39198430
Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry [ Nat Commun, 2024, 15(1):3220] PubMed: 38622115
Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma [ Clin Cancer Res, 2024, 30(4):703-718] PubMed: 37695642
Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution [ Cell Mol Life Sci, 2024, 81(1):29] PubMed: 38212474
Cyclin-dependent kinase inhibitors enhance programmed cell death protein 1 immune checkpoint blockade efficacy in triple-negative breast cancer by affecting the immune microenvironment [ Cancer, 2024, 130(S8):1449-1463] PubMed: 38482921
HER4 Affects Sensitivity to Tamoxifen and Abemaciclib in Luminal Breast Cancer Cells and Restricts Tumor Growth in MCF-7-Based Humanized Tumor Mice [ Int J Mol Sci, 2024, 25(13)7475] PubMed: 39000582
Targeting Tyro3, Axl, and MerTK Receptor Tyrosine Kinases Significantly Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibition [ Cancers (Basel), 2024, 16(12)2253] PubMed: 38927958

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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