Home Cell Cycle CDK inhibitor LY2835219 (Abemaciclib) Mesylate

연구용

LY2835219 (Abemaciclib) Mesylate CDK4/6 inhibitor

제품 번호S7158

Abemaciclib mesylate is a potent and selective inhibitor of CDK4 and CDK6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively. Phase 3.
LY2835219 (Abemaciclib) Mesylate CDK inhibitor Chemical Structure

화학 구조

분자량: 602.7

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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
human COLO205 cells Function assay 24 h 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 26115571
human 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 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=2 nM 26115571
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=0.6 nM 26115571
HCT116 Antiproliferative assay 72 hrs IC50 = 0.54 μM 30165341
MCF7 Antiproliferative assay 72 hrs IC50 = 0.71 μM 30165341
PANC1 Antiproliferative assay 72 hrs IC50 = 5.94 μM 30165341
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 activity against human 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 activity against human 96 hrs Antiproliferative activity against human COLO205 cells after 96 hrs by CCK8 assay, IC50 = 0.217 μM. 29459274
MDA-MB-468 Antiproliferative activity against human 96 hrs Antiproliferative activity against human MDA-MB-468 cells after 96 hrs by CCK8 assay, IC50 = 4.808 μM. 29459274
COLO205 Inhibition of CDK4 in human 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 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 602.7 화학식

C27H32F2N8.CH4O3S

 보관 (수령일로부터)
CAS 번호 1231930-82-7 SDF 다운로드 원액 보관

동의어 LY2835219 mesylate 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.CS(=O)(=O)O

용해도 (Solubility)

In vitro
배치:

Water : 100 mg/mL

DMSO : 24 mg/mL (39.82 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 13 mg/mL

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)

LY2835219 is an orally available cyclin-dependent kinase (CDK) inhibitor that targets the CDK4 (cyclin D1) and CDK6 (cyclin D3) cell cycle pathway, with potential antineoplastic activity. 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, as seen in certain types of cancer, causes cell cycle deregulation.

생체 내(In vivo)

LY2835219 saturates BBB efflux with an unbound plasma IC50 of about 95 nM. The percent of dose in brain for LY2835219-MsOH is 0.5–3.9%. In both a subcutaneous and intracranial human glioblastoma model (U87MG), LY2835219-MsOH suppressed tumor growth in a dose-dependent manner both as a single agent, and in combination with temozolomide.

참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-Rb(S780) / Rb / p21 p-ERK / ERK / p-Akt / Akt / p-mTOR(S2448) / mTOR pRb(S795) / E2F1 / Cyclin A2 / Cyclin E2
S7158-WB1
26909611
Growth inhibition assay Cell viability
S7158-viability
26909611

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

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
Is your product S7158 “mesylate salt form”?

답변:
It is the mesylate salt form of our S7158 LY2835219.