Home Cell Cycle PLK inhibitor Volasertib (BI6727)

연구용

Volasertib (BI6727) PLK1 inhibitor

제품 번호: S2235

Volasertib is a highly potent Plk1 inhibitor with IC50 of 0.87 nM in a cell-free assay. It shows 6- and 65-fold greater selectivity against Plk2 and Plk3. Volasertib induces cell cycle arrest and apoptosis in various cancer cells. Phase 3.
Volasertib (BI6727) PLK inhibitor Chemical Structure

화학 구조

분자량: 618.81

바로가기

품질 관리 (Quality Control)

배치: 순도: 99.78%
99.78

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
KASUMI-1 Growth Inhibition Assay 72 h IC50=170±51 nM 25576074
KG-1 Growth Inhibition Assay 72 h IC50=150±67 nM 25576074
MOLM-13 Growth Inhibition Assay 72 h IC50=57±44 nM 25576074
MV-4-11 Growth Inhibition Assay 72 h IC50=16±6 nM 25576074
NOMO-1 Growth Inhibition Assay 72 h IC50=145±7 nM 25576074
OCI-AML3 Growth Inhibition Assay 72 h IC50=90±51 nM 25576074
SKM-1 Growth Inhibition Assay 72 h IC50=95±52 nM 25576074
THP-1 Growth Inhibition Assay 72 h IC50=56±39 nM 25576074
MCF7/LTED  Growth Inhibition Assay 2.5-40 nM 5 d inhibits cell growth in a dose-dependent manner 25480943
HCC1428/LTED Growth Inhibition Assay 2.5-40 nM 5 d inhibits cell growth in a dose-dependent manner 25480943
A431 Growth Inhibition Assay 0-30 nM 1-4 d inhibits cell growth in both dose- and time-dependent manner 23891096
FaDu  Growth Inhibition Assay 0-1000 nM 1-4 d inhibits cell growth in both dose- and time-dependent manner 23891096
SF188 Growth Inhibition Assay 50-150 nM 72 h DMSO inhibits cell proliferation 23887645
T98G Growth Inhibition Assay 50-150 nM 72 h DMSO inhibits cell proliferation 23887645
DU145 Growth Inhibition Assay 10/50/250 nM 24 h IC50<10 nM 23884428
LNCaP Growth Inhibition Assay 10/50/250 nM 24 h IC50<10 nM 23884428
PC3 Growth Inhibition Assay 10/50/250 nM 24 h IC50∼600 nM 23884428
RT4 Growth Inhibition Assay 48 h IC50=111.27 nM 23792639
5637 Growth Inhibition Assay 48 h IC50=1165.14 nM 23792639
T24 Growth Inhibition Assay 48 h IC50=204.91 nM 23792639
KMCH-1 Apoptosis Assay 200 nM 24 h induces apoptosis 23703673
Mz-ChA-1 Apoptosis Assay 200 nM 24 h induces apoptosis 23703673
HUCCT-1 Apoptosis Assay 200 nM 24 h induces apoptosis 23703673
HCT 116 Growth Inhibition Assay EC50 = 23 nM 19383823
NCI-H460 Growth Inhibition Assay EC50 = 21 nM 19383823
BRO Growth Inhibition Assay EC50 = 11 nM 19383823
GRANTA-519 Growth Inhibition Assay EC50 = 15 nM 19383823
HL-60 Growth Inhibition Assay EC50 = 32 nM 19383823
THP-1 Growth Inhibition Assay EC50 = 36 nM 19383823
Raji Growth Inhibition Assay EC50 = 37 nM 19383823
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
SKBR3 Cytotoxicity assay 24 hrs Cytotoxicity against human SKBR3 cells after 24 hrs by MTT assay 29288948
MDA-MB-231 Cytotoxicity assay 24 hrs Cytotoxicity against human MDA-MB-231 cells after 24 hrs by MTT assay 29288948
MDA-MB-468 Cytotoxicity assay 24 hrs Cytotoxicity against human MDA-MB-468 cells after 24 hrs by MTT assay 29288948
BT474 Cytotoxicity assay 24 hrs Cytotoxicity against human BT474 cells after 24 hrs by MTT assay 29288948
ZR-75-1 Cytotoxicity assay 24 hrs Cytotoxicity against human ZR-75-1 cells after 24 hrs by MTT assay 29288948
클릭하여 더 많은 세포주 실험 데이터 보기

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 618.81 화학식

C34H50N8O3

 보관 (수령일로부터)
CAS 번호 755038-65-4 SDF 다운로드 원액 보관

동의어 BI 6727 Smiles CCC1C(=O)N(C2=CN=C(N=C2N1C(C)C)NC3=C(C=C(C=C3)C(=O)NC4CCC(CC4)N5CCN(CC5)CC6CC6)OC)C

용해도 (Solubility)

In vitro
배치:

DMSO : 35 mg/mL (56.56 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : 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)

특징
A high volume of distribution, indicating good tissue penetration, and a long terminal half-life.
Targets/IC50/Ki
PLK1
(Cell-free assay)
0.87 nM
시험관 내(In vitro)

Like BI2536, BI6727 is an ATP-competitive kinase inhibitor from the dihydropteridinone class of compounds. In addition to Plk1, this compound also potently inhibits two closely related kinases Plk2 and Plk3 with IC50 of 5 nM and 56 nM, respectively. This chemical at concentrations up to 10 μM displays no inhibitory activity against a panel of >50 other kinases. It inhibits the proliferation of multiple cell lines derived from various cancer tissues, including HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji cells with EC50 of 23 nM, 21 nM, 11 nM, 15 nM, 32 nM, 36 nM, and 37 nM, respectively. This compound treatment (100 nM) in NCI-H460 cells induces an accumulation of mitotic cells with monopolar spindles and positive staining for histone H3 phosphoserine 10, confirming that cells are arrested early in the M phase, followed by induction of apoptosis. Low nanomolar concentrations of this inhibitor display potent inhibitory activity against neuroblastoma (NB) tumor-initiating cells (NB TIC) with EC50 of 21 nM, whereas only micromolar concentrations of it are cytotoxic for normal pediatric neural stem cells. It induces growth arrest of Daoy and ONS-76 medulloblastoma cells similar to BI 2536.

키나아제 분석
In vitro kinase assays
Recombinant human Plk1 (residues 1-603) is expressed as NH2-terminal, GST-tagged fusion protein using a baculoviral expression system and purified by affinity chromatography using glutathione-agarose. Enzyme activity assays for Plk1 are done in the presence of serially diluted this compound using 20 ng of recombinant kinase and 10 μg casein from bovine milk as substrate. Kinase reactions are done in a final volume of 60 μL for 45 minutes at 30 °C [15 mM MgCl2, 25 mM MOPS (pH 7.0), 1 mM DTT, 1% DMSO, 7.5 μM ATP, 0.3 μCi γ-32P-ATP]. Reactions are terminated by the addition of 125 μL of ice-cold 5% TCA. After transferring the precipitates to MultiScreen mixed ester cellulose filter plates, plates are washed with 1% TCA and quantified radiometrically. Dose-response curves are used for calculating IC50 value.
생체 내(In vivo)

Administration of BI6727 significantly inhibits the growth of multiple human carcinoma xenografts including HCT116, NCI-H460, and taxane-resistant CXB1 colon carcinoma, accompanied by an increase in the mitotic index as well as an increase in apoptosis. In in vivo studies, this compound shows better toxicity and pharmacokinetic profile compared to BI2536.

참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot Fibronectin / β-integrin / p-vimentin / Vimentin / p-HH3 p-c-Met / c-Met / p-FAK / FAK / p-Src / Src PARP / c-myc p-AKT / AKT / p-MAPK / MAPK p-PLK1 / PLK1
S2235-WB5
31040125
Immunofluorescence PLK1 / Wee1
S2235-IF1
29108241
Growth inhibition assay Cell viability
S2235-viability1
29383095

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT02722135 Withdrawn
Leukemia Myeloid Acute
Boehringer Ingelheim
 November 2016 Phase 1
NCT02721875 Terminated
Myelodysplastic Syndromes
Boehringer Ingelheim
 April 28 2016 Phase 1
NCT02201329 Completed
Myelodysplastic Syndromes|Leukemia Myelomonocytic Chronic
Boehringer Ingelheim
 August 2014 Phase 1
NCT01971476 Completed
Leukemia|Neoplasms
Boehringer Ingelheim
 October 22 2013 Phase 1
NCT01772563 Completed
Neoplasms
Boehringer Ingelheim
 February 4 2013 Phase 1
NCT01662505 Completed
Leukemia Myeloid Acute
Boehringer Ingelheim
 August 2012 Phase 1

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
I wonder how to reconstitute it for in vivo studies?

답변:
It can be dissolved in 4% DMSO+Corn oil at 2mg/ml for i.p. injection in mice. For oral administration, this compound can be formulated in hydrochloric acid (0.1 N), and diluted with 0.9% NaCl, or suspended in 0.5% Natrosol 250 hydroxyethyl-cellulose as indicated in the publications. We also suggest the vehicle 30% PEG400/0.5% Tween80/5% propylene glycol for a suspension which we tested in house.