Abemaciclib

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

CAS No. 1231929-97-7

サイズ	価格(税別)	在庫状況
5mg	JPY 22000	国内在庫あり
25mg	JPY 43500	国内在庫あり
100mg	JPY 59800	国内在庫あり
1g	JPY 295500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（97）

製品安全説明書

現在のバッチを見る：純度： 99.97%

99.97

Abemaciclibと併用されることが多い化合物

Palbociclib (PD-0332991) HCl

Abemaciclib and Palbociclib HCl are CDK4/6 inhibitors that inhibit SARS-CoV-2 replication in AT2 and NKX2-5 cells.

Rudraraju R, et al. Stem Cell Reports. 2023 Jun 13;18(6):1308-1324.

Ribociclib

Abemaciclib and Ribociclib have been approved by the FDA for their use together with endocrine therapy such as aromatase inhibitors (AIs) or fulvestrant as therapeutic options for treatment of breast cancer.

Eggersmann TK, et al. BioDrugs. 2019 Apr;33(2):125-135.

Olaparib (AZD2281)

Ademaciclib and Olaparib combination treatment increases the percentage of sub-G₁ cells to a great extent in C4–2b, C4–2b-ENZR, and NCI-H660 models.

Wu C, et al. Mol Cancer Ther. 2021 Sep;20(9):1680-1691.

Trametinib (GSK1120212)

Abemaciclib with Trametinib synergistically reduces the survival of the RAS-mutant RMS cell line RD.

Candido MF, et al. Pharmaceutics. 2023 Feb 16;15(2):664.

Paclitaxel

Abemaciclib and Paclitaxel are effective in inhibiting tumor growth compared to paclitaxel alone in cervical cancer mouse model.

Liu Y, et al. Fundam Clin Pharmacol. 2021 Feb;35(1):156-164.

Abemaciclib関連製品

関連ターゲット	CDK1 CDK2 CDK3 CDK4 CDK5 CDK6 CDK7 CDK9 CLK Cdc CDK8 CDK12 CDK13 CDK19 CDK11 CDK/cyclin complexes	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library MAPK Inhibitor Library DNA Damage/DNA Repair compound Library Cell Cycle compound library	もっと見る

シグナル伝達経路

CDKシグナル伝達経路

CDK阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
COLO205	Function assay	0.1 to 10 uM	24 hrs	Inhibition of CDK4 in human COLO205 cells assessed as reduction in total Rb protein level at 0.1 to 10 uM after 24 hrs by immunoblotting method	29459274
COLO205	Cell cycle arrest assay	up to 10 uM	24 hrs	Cell cycle arrest in human COLO205 cells assessed as accumulation at G2/M phase up to 10 uM after 24 hrs by propidium iodide staining based FACS analysis	29459274
MHH-ES-1	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
CHLA-258	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
ES-3	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
ES-1	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
RD-ES	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
A673	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
TC-71	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
ES-7	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
Cado-ES-1	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
SK-ES-1	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
COLO205 cells	Function assay		24 h	Inhibition of CDK4/6 in human COLO205 cells assessed as inhibition of Rb phosphorylation after 24 hrs by propidium iodide staining-based laser-scanning fluorescence microplate cytometric analysis, IC50=0.12 μM	26115571
ES-8	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
EW8	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
ES-6	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
ES-2	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
SMS-CTR	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
ES-4	Proliferation assay		96 hours	antiproliferative effects with an absolute EC50 value below 1 μmol/L	30131386
CT26	Cell viability assay		96 hours	IC50=2.7 μM	29539425
insect cells	Function assay		50 mins	Competitive inhibition of human CDK4/cyclin D1 expressed in insect cells assessed as phosphorylation of CTRF after 50 mins by Michaelis-Menten plot analysis in presence of ATP, Ki = 0.0006 μM.	26115571
insect cells	Function assay		50 mins	Inhibition of human CDK4/cyclin D1 expressed in insect cells assessed as phosphorylation of CTRF after 50 mins by microplate scintillation counter, IC50 = 0.002 μM.	26115571
COLO205	Function assay		24 hrs	Inhibition of CDK4/6 in human COLO205 cells assessed as maximum cell cycle arrest at G1 phase after 24 hrs by propidium iodide staining-based flow cytometric analysis, INH = 6.7 μM.	26115571
Sf9	Function assay		90 mins	Inhibition of recombinant human N-terminal GST-tagged CDK4 (4 to 303 residues)/cyclin D1 (4 to 295 residues) expressed in sf9 cells using C-terminal retinoblastoma fragment as substrate after 90 mins by [gamma-33P]ATP based microbeta scintillation countin, Ki = 0.002 μM.	27171036
Sf9	Function assay		90 mins	Inhibition of recombinant full length human N-terminal GST-tagged CDK6 (1 to 326 residues)/cyclin D1 (4 to 295 residues) expressed in sf9 cells using C-terminal retinoblastoma fragment as substrate after 90 mins by [gamma-33P]ATP based microbeta scintilla, Ki = 0.01 μM.	27171036
COLO205	Antiproliferative assay		96 hrs	Antiproliferative activity against human COLO205 cells after 96 hrs by CCK-8 assay, IC50 = 0.46 μM.	29074254
U87MG	Antiproliferative assay		72 hrs	Antiproliferative activity against human U87MG cells after 72 hrs by DAPI staining based assay, IC50 = 0.0481 μM.	29247857
Sf9	Function assay		90 mins	Inhibition of recombinant human full length CDK6 expressed in baculovirus infected Sf9 insect cells using histone H1 substrate after 90 mins by ADP-Glo assay, IC50 = 0.0078 μM.	29429832
Sf9	Function assay		90 mins	Inhibition of recombinant human full length CDK1/Cyclin D3 expressed in baculovirus infected Sf9 insect cells using histone H1 substrate after 90 mins by ADP-Glo assay, IC50 = 0.056 μM.	29429832
MDA-MB-231	Antiproliferative assay		72 hrs	Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by DAPI staining based assay, IC50 = 0.191 μM.	29429832
COLO205	Antiproliferative assay		96 hrs	Antiproliferative activity against human COLO205 cells after 96 hrs by CCK8 assay, IC50 = 0.217 μM.	29459274
MDA-MB-468	Antiproliferative assay		96 hrs	Antiproliferative activity against human MDA-MB-468 cells after 96 hrs by CCK8 assay, IC50 = 4.808 μM.	29459274
Sf9	Function assay			Inhibition of CDK1/Cyclin B (unknown origin) expressed in baculoviral infected insect Sf9 cells using histone H1 as substrate in presence of [gamma-33P]ATP, IC50 = 0.371 μM.	26741853
Sf21	Function assay			Inhibition of recombinant human full length C-terminal His6-tagged CDK7/cyclin H/N-terminal GST-tagged MAT1 expressed in baculovirus infected Sf21 insect cells using cdk7 substrate peptide, Ki = 3.91 μM.	27171036
Sf9	Function assay			Inhibition of recombinant human N-terminal GST-tagged CDK4 (S4 to E303 residues)/Cyclin D1 (Q4 to I295 residues) expressed in sf9 cells using Rb protein (773 to 928 residues) as substrate in presence of [33P]-ATP by scintillation counting method, IC50 = 0.002 μM.	29429832
Sf9	Function assay			Inhibition of recombinant human N-terminal GST-tagged CDK4 (M1 to A326 residues)/Cyclin D1 (Q4 to I295 residues) expressed in sf9 cells using Rb protein (773 to 928 residues) as substrate in presence of [33P]-ATP by scintillation counting method, IC50 = 0.01 μM.	29429832
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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.

Targets

CDK4 ^[1] (Cell-free assay)	CDK6 ^[1] (Cell-free assay)
2 nM	10 nM

In Vitro
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].
細胞実験	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.
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	Western blot	p-Rb / Rb / p-EGFR / EGFR / p-HER2 / HER2 / p-HER3 / HER3 / p-P70S6K / P70S6K / p-S6RP / S6RP / Cyclin D1 β-catenin GSK3β / CAMKII pan CDK6 / CDK4 / AXL		26977878

In Vivo
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].
動物実験	動物モデル	Athymic nude mice implanted with human NSCLC xenograft tumors
	投与量	25, 50, or 100 mg/kg/d
	投与経路	oral

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT06139107	Not yet recruiting	Breast Cancer	Mridula George MD\|Rutgers The State University of New Jersey	December 21 2023	Phase 1
NCT06169371	Recruiting	Breast Cancer	University of Illinois at Chicago	December 2023	Phase 4

参考
[1] Corona SP, et al. Drug Des Devel Ther. 2018, 12:321-330. [2] Patnaik A, et al. Cancer Discov. 2016, 6(7):740-53. [3] Schaer DA, et al. Cell Rep. 2018, 22(11):2978-2994.

参考

化学情報

分子量	506.59	化学式	C₂₇H₃₂F₂N₈
CAS No.	1231929-97-7	SDF	--
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
保管	3 years -20°C powder	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3 years -20°C powder	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

Ethanol : 8 mg/mL

DMSO : 6 mg/mL ( (11.84 mM)； Warmed with 50℃ water bath; 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):