Home Cell Cycle CDK inhibitor Abemaciclib (LY2835219)

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Abemaciclib (LY2835219) CDK4/6 inhibitor

제품 번호S5716

Abemaciclib is a cell cycle inhibitor selective for CDK4/6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively.
Abemaciclib (LY2835219) CDK inhibitor Chemical Structure

화학 구조

분자량: 506.59

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품질 관리 (Quality Control)

배치: 순도: 99.97%
99.97

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
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
SK-ES-1 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
ES-7 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
A673 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
ES-1 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
CHLA-258 Proliferation assay 96 hours antiproliferative effects with an absolute EC50 value below 1 μmol/L 30131386
MHH-ES-1 Proliferation assay 96 hours antiproliferative effects with an absolute EC50 value below 1 μmol/L 30131386
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 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
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
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
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 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 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 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
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
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
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 506.59 화학식

C27H32F2N8

 보관 (수령일로부터) 3 years -20°C powder
CAS 번호 1231929-97-7 -- 원액 보관

동의어 LY2835219 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

용해도 (Solubility)

In vitro
배치:

Ethanol : 8 mg/mL

DMSO : 6 mg/mL (11.84 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

Targets/IC50/Ki
CDK4
(Cell-free assay)
2 nM
CDK6
(Cell-free assay)
10 nM
시험관 내(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. Consistent with its activity against CDK4 and CDK6, abemaciclib inhibits RB phosphorylation and leads to G1 arrest in RB-proficient cell lines. 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.
생체 내(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.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot CDK6 / CDK4 / AXL GSK3β / CAMKII pan β-catenin p-Rb / Rb / p-EGFR / EGFR / p-HER2 / HER2 / p-HER3 / HER3 / p-P70S6K / P70S6K / p-S6RP / S6RP / Cyclin D1
S5716-WB1
29133594

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT06139107 Recruiting
Breast Cancer
Mridula George MD|Rutgers The State University of New Jersey
 June 21 2024 Phase 1
NCT06259929 Not yet recruiting
Breast Cancer
Fondazione Oncotech
 April 1 2024 Phase 2