Abemaciclib

製品コードS5716 バッチS571605

印刷

化学情報

Synonyms

LY2835219

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₂₇H₃₂F₂N₈

分子量

506.59

CAS No.

1231929-97-7

Solubility (25°C)*

体外

Ethanol (warmed with 50ºC water bath)

11 mg/mL (21.71 mM)

DMSO (warmed with 50ºC water bath)

4 mg/mL (7.89 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

5%DMSO 1 Corn oil

0.2mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 4 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Abemaciclib is a cell cycle inhibitor selective for CDK4/6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively.
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].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	CT26 tumor cell line
	濃度	0-10 μM
	反応時間	96 h
	実験の流れ	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.
動物実験	動物モデル	Athymic nude mice implanted with human NSCLC xenograft tumors
	投薬量	25, 50, or 100 mg/kg/d
	投与方法	oral

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment [ Cancer Cell, 2024, S1535-6108(24)00037-0]	PubMed: 38402610
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
Modulation of autophagy and apoptosis can contribute to the anticancer effect of Abemaciclib/Celecoxib combination in colon cancer cells [ Med Oncol, 2024, 41(2):43]	PubMed: 38170401
p21 Prevents the Exhaustion of Cluster of Differentiation 4-Positive T Cells Within the Antitumor Immune Response Against Colorectal Cancer [ Gastroenterology, 2023, S0016-5085(23)05008-4]	PubMed: 37734420
Single-cell morphological and topological atlas reveals the ecosystem diversity of human breast cancer [ Nat Commun, 2023, 14(1):6796]	PubMed: 37880211
Single-cell morphological and topological atlas reveals the ecosystem diversity of human breast cancer [ Nat Commun, 2023, 10.1038/s41467-023-42504-y]	PubMed: 37880211
Molecular mechanisms of tubulogenesis revealed in the sea star hydro-vascular organ [ Nat Commun, 2023, 14(1):2402]	PubMed: 37160908
Co-targeting RANK pathway treats and prevents acquired resistance to CDK4/6 inhibitors in luminal breast cancer [ Cell Rep Med, 2023, 4(8):101120]	PubMed: 37451269

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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