Home Cell Cycle CDK inhibitor Dinaciclib (SCH 727965)

연구용

Dinaciclib (SCH 727965) CDK inhibitor

제품 번호: S2768

Dinaciclib is a novel and potent CDK inhibitor for CDK2, CDK5, CDK1 and CDK9 with IC50 of 1 nM, 1 nM, 3 nM and 4 nM in cell-free assays, respectively. It also blocks thymidine (dThd) DNA incorporation. Dinaciclib induces apoptosis through the activation of caspases 8 and 9. Phase 3.
Dinaciclib (SCH 727965) CDK inhibitor Chemical Structure

화학 구조

분자량: 396.49

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품질 관리 (Quality Control)

배치: 순도: 99.99%
99.99

함께 자주 사용되는 제품 Dinaciclib (SCH 727965)

MK-2206 Dihydrochloride

It and MK-2206 2HCl combination use dramatically blocks tumor growth and markedly reduces the number of metastatic lesions in the orthotopic Panc265/Panc253 models.

SCH772984

It and SCH772984 combination use results in a more significant reduction in tumor growth than either treatment alone in mice.

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
CA46 Apoptosis Assay 100 nM 24 h induces cell cycle arrest 25289887
Kasumi-1 Apoptosis Assay 100 nM 24 h induces cell cycle arrest 25289887
U937 Function Assay 2/5/10 nM 3 h blocks induction of XBP-1s and downstream targets 24362465
8226 Function Assay 2/5/10 nM 4 h blocks induction of XBP-1s and downstream targets 24362465
H929 Function Assay 2/5/10 nM 4 h blocks induction of XBP-1s and downstream targets 24362465
K562 Function Assay 1.5/3/8 nM 6 h blocks induction of XBP-1s and downstream targets 24362465
BaF3/Bcr-abl Function Assay 1.5/3/8 nM 6 h blocks induction of XBP-1s and downstream targets 24362465
U937  Function Assay 2/10 nM 3 h blocks induction of XBP-1s and downstream targets 24362465
1205Lu Growth Inhibition Assay 10/30 nM 72 h inhibits cell growth and survival 23527225
WM1366 Growth Inhibition Assay 10/30 nM 72 h inhibits cell growth and survival 23527225
RD Growth Inhibition Assay IC50=8.2 nM 22315240
Rh41 Growth Inhibition Assay IC50=10.5 nM 22315240
Rh18 Growth Inhibition Assay IC50=10.5 nM 22315240
Rh30 Growth Inhibition Assay IC50=9 nM 22315240
BT-12 Growth Inhibition Assay IC50=8.5 nM 22315240
CHLA-266 Growth Inhibition Assay IC50=7.3 nM 22315240
TC-71 Growth Inhibition Assay IC50=3.9 nM 22315240
CHLA-9 Growth Inhibition Assay IC50=8 nM 22315240
CHLA-10 Growth Inhibition Assay IC50=6.3 nM 22315240
CHLA-258 Growth Inhibition Assay IC50=9.9 nM 22315240
GBM2 Growth Inhibition Assay IC50=6.5 nM 22315240
NB-1643 Growth Inhibition Assay IC50=3.3 nM 22315240
NB-EBc1 Growth Inhibition Assay IC50=7 nM 22315240
CHLA-90 Growth Inhibition Assay IC50=7.5 nM 22315240
CHLA-136 Growth Inhibition Assay IC50=9.8 nM 22315240
NALM-6 Growth Inhibition Assay IC50=4.6 nM 22315240
COG-LL-317 Growth Inhibition Assay IC50=6.5 nM 22315240
RS4;11 Growth Inhibition Assay IC50=5.1 nM 22315240
MOLT-4 Growth Inhibition Assay IC50=9.3 nM 22315240
CCRF-CEM Growth Inhibition Assay IC50=5.6 nM 22315240
Kasumi-1 Growth Inhibition Assay IC50=4.5 nM 22315240
Karpas-299 Growth Inhibition Assay IC50=3.9 nM 22315240
Ramos-RA1 Growth Inhibition Assay IC50=7.9 nM 22315240
MIAPaCa-2 Growth Inhibition Assay 72 h GI50=10 nM 21768779
Pa20C  Growth Inhibition Assay 72 h GI50=20 nM 21768779
ML-1 Apoptosis Assay 1-1000 nM 4 h induces apoptosis slightly 21768777
Cytotoxicity assay MDA-MB-436 72 hrs IC50 = 0.005 μM 23600925
Cytotoxicity assay NCI-H929 72 hrs IC50 = 0.005 μM 23600925
Cytotoxicity assay MDA-MB-231 72 hrs IC50 = 0.005 μM 23600925
Cytotoxicity assay SK-ES-1 72 hrs IC50 = 0.005 μM 23600925
Cytotoxicity assay A673 72 hrs IC50 = 0.005 μM 23600925
Cytotoxicity assay SK-BR-3 72 hrs IC50 = 0.005 μM 23600925
Cytotoxicity assay MNNG-HOS 72 hrs IC50 = 0.0055 μM 23600925
Cytotoxicity assay SK-UT-1 72 hrs IC50 = 0.006 μM 23600925
Cytotoxicity assay U266 72 hrs IC50 = 0.006 μM 23600925
Cytotoxicity assay RPMI18226 72 hrs IC50 = 0.009 μM 23600925
Cytotoxicity assay SW872 72 hrs IC50 = 0.0095 μM 23600925
Cytotoxicity assay T47D 72 hrs IC50 = 0.01 μM 23600925
Apoptosis assay A673 24 hrs EC50 = 0.011 μM 23600925
Cytotoxicity assay MCF7 72 hrs IC50 = 0.02 μM 23600925
Function assay Sf9 IC50 = 0.072 μM 26741853
Function assay sf9 IC50 = 0.002 μM 26851505
Function assay Sf9 1 hr IC50 = 0.001 μM 27171036
Function assay Sf9 1 hr IC50 = 0.001 μM 27171036
Function assay Sf9 1 hr IC50 = 0.001 μM 27171036
Function assay Sf9 1 hr IC50 = 0.001 μM 27171036
Function assay Sf9 1 hr IC50 = 0.003 μM 27171036
Function assay Sf9 1 hr IC50 = 0.003 μM 27171036
Function assay Sf9 1 hr IC50 = 0.004 μM 27171036
Function assay Sf9 1 hr IC50 = 0.004 μM 27171036
Function assay Sf9 10 uM IC50 = 0.004 μM 29329658
Function assay Sf9 1 hr IC50 = 0.001 μM 29853338
Function assay Sf9 1 hr IC50 = 0.001 μM 29853338
Function assay Sf9 1 hr IC50 = 0.003 μM 29853338
Function assay Sf9 1 hr IC50 = 0.004 μM 29853338
Antiproliferative assay MOLM13 72 hrs GI50 = 0.0033 μM 30253346
Antiproliferative assay MEC1 72 hrs GI50 = 0.0036 μM 30253346
Antiproliferative assay MOLM14 72 hrs GI50 = 0.0045 μM 30253346
Antiproliferative assay COLO205 72 hrs GI50 = 0.0068 μM 30253346
Antiproliferative assay HL60 72 hrs GI50 = 0.008 μM 30253346
Antiproliferative assay Ramos 72 hrs GI50 = 0.0086 μM 30253346
Antiproliferative assay GISTT1 72 hrs GI50 = 0.0088 μM 30253346
Antiproliferative assay U937 72 hrs GI50 = 0.01 μM 30253346
Antiproliferative assay A431 72 hrs GI50 = 0.011 μM 30253346
Antiproliferative assay SKM1 72 hrs GI50 = 0.011 μM 30253346
Antiproliferative assay MEC2 72 hrs GI50 = 0.011 μM 30253346
Antiproliferative assay A375 72 hrs GI50 = 0.011 μM 30253346
Antiproliferative assay OCI-AML3 72 hrs GI50 = 0.013 μM 30253346
Antiproliferative assay BE(2)-M17 72 hrs GI50 = 0.021 μM 30253346
Antiproliferative assay CHO 72 hrs GI50 = 0.16 μM 30253346
Function assay NCI-H929 0.005 uM 24 hrs Inhibition of CDK2-mediated Rb phosphorylation at Ser 807/811 in human NCI-H929 cells at 0.005 uM after 24 hrs by immunoblotting analysis 23600925
Function assay A673 0.05 uM 24 hrs Inhibition of CDK2-mediated Rb phosphorylation at Ser 807/811 in human A673 cells at 0.05 uM after 24 hrs by immunoblotting analysis 23600925
Apoptosis assay MEC1 0.01 uM 24 hrs Induction of apoptosis in human MEC1 cells assessed as decrease in MCL-1 level at 0.01 uM after 24 hrs by immunoblotting analysis 30253346
Apoptosis assay HL60 0.01 uM 24 hrs Induction of apoptosis in human HL60 cells assessed as decrease in MCL-1 level at 0.01 uM after 24 hrs by immunoblotting analysis 30253346
Apoptosis assay MV4-11 0.01 uM 24 hrs Induction of apoptosis in human MV4-11 cells assessed as decrease in c-MYC level at 0.01 uM after 24 hrs by immunoblotting analysis 30253346
Apoptosis assay MEC1 0.01 uM 24 hrs Induction of apoptosis in human MEC1 cells assessed as decrease in c-MYC level at 0.01 uM after 24 hrs by immunoblotting analysis 30253346
Apoptosis assay MV4-11 0.01 uM 24 hrs Induction of apoptosis in human MV4-11 cells assessed as decrease in MCL-1 level at 0.01 uM after 24 hrs by immunoblotting analysis 30253346
Apoptosis assay HL60 0.01 uM 24 hrs Induction of apoptosis in human HL60 cells assessed as decrease in c-MYC level at 0.01 uM after 24 hrs by immunoblotting analysis 30253346
Cytotoxicity assay U2OS 96 hrs IC50 = 0.006 μM ChEMBL
Function assay U2OS 1 hr IC50 = 0.007 μM ChEMBL
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량 396.49 화학식

C21H28N6O2

 보관 (수령일로부터)
CAS 번호 779353-01-4 SDF 다운로드 원액 보관

동의어 SCH727965, PS-095760 Smiles CCC1=C2N=C(C=C(N2N=C1)NCC3=C[N+](=CC=C3)[O-])N4CCCCC4CCO

용해도 (Solubility)

In vitro
배치:

DMSO : 79 mg/mL (199.24 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 35 mg/mL

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
CDK2
(Cell-free assay)
1 nM
CDK5
(Cell-free assay)
1 nM
CDK1
(Cell-free assay)
3 nM
CDK9
(Cell-free assay)
4 nM
시험관 내(In vitro)

Dinaciclib is also a potent DNA replication inhibitor that blocks thymidine (dThd) DNA incorporation in A2780 cells with IC50 of 4 nM. This compound strongly suppresses phosphorylation of Rb on Ser 807/811 at concentrations >6.25 nM, which is in agreement with the observation that 4 nM concentrations are required for 50% inhibition of dThd DNA incorporation in the same cell model. Significantly, complete suppression of Rb phosphorylation is correlated with the onset of apoptosis, as indicated by the appearance of the p85 PARP cleavage product in cells exposed to >6.25 nM of this chemical. It is active against a broad spectrum of human tumor cell lines. Addition of this compound during exposure also suppresses accumulation of γ-H2AX, in a dose-dependent manner. It inhibits melanoma cell proliferation, and drives melanoma cells into massive apoptosis. This chemical induces the apoptosis of several osteosarcoma cell lines including those resistant to doxorubicin. It attenuates the phosphorylation of RNAP II at serine 2 and the phosphorylation of the CDK inhibitor p27Kip1 at threonine 187. Reductions in phosphorylation activity occurrs at 12 - 40 nM of this compound (4 to 16 hours post-addition). It also reduces the phosphorylation of Rb at serine 807/811. This chemical induces the apoptosis of mock- and p53-depleted U2OS cells to a similar extent.

키나아제 분석
Cyclin/CDK kinase assay
Recombinant cyclin/CDK holoenzymes are purified from Sf9 cells engineered to produce baculoviruses that express a specific cyclin or CDK. Cyclin/CDK complexes are typically diluted to a final concentration of 50 μg/mL in a kinase reaction buffer containing 50 mM Tris-HCl (pH 8.0), 10 mM MgCl2, 1 mM DTT, and 0.1 mM sodium orthovanadate. For each kinase reaction, 1 μg of enzyme and 20 μL of a 2-μM substrate solution (a biotinylated peptide derived from histone H1) are mixed and combined with 10 μL of diluted this compound. The reaction is started by the addition of 50 μL of 2 μM ATP and 0.1 μCi of 33P-ATP. Kinase reactions are incubated for 1 hour at room temperature and are stopped by the addition of 0.1% Triton X-100, 1 mM ATP, 5 mM EDTA, and 5 mg/mL streptavidin-coated SPA beads. SPA beads are captured using a 96-well GF/B filter plate and a Filtermate universal harvester. Beads are washed twice with 2 M NaCl and twice with 2 M NaCl containing 1% phosphoric acid. The signal is then assayed using a TopCount 96-well liquid scintillation counter.
생체 내(In vivo)

Dinaciclib i.p. administration at 8, 16, 32, and 48 mg/kg daily for 10 days results in tumor inhibition by 70%, 70%, 89%, and 96%, respectively. This compound's MED (minimum effective dose) appears to be <8 mg/kg. It is well tolerated, and the maximum body weight loss in the highest dosage group is 5%. This chemical has dose-dependent antitumor activity in vivo, and that nearly complete inhibition of tumor growth occurs at a dose level below the MTD (maximum tolerated dose). It has a short plasma half-life in mouse.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/21490307/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot Mcl-1 / Bcl-2 / Bcl-xl / Bax / Bak / PUMA / Noxa Cleaved PARP / c-Myc Survivin RNAP II (P-Ser2/P-Ser5)
S2768-WB1
28714472
Growth inhibition assay Cell viability Cell viability
S2768-viability1
27378523
Immunofluorescence cyclin B1 / α-tubulin / Aurora A OCT4
S2768-IF1
28207834

임상시험 정보 (Clinical Trial Information)

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

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT03484520 Terminated
Cancer - Acute Myeloid Leukemia
AbbVie|Merck Sharp & Dohme LLC
 July 23 2018 Phase 1
NCT01434316 Active not recruiting
Advanced Malignant Solid Neoplasm
National Cancer Institute (NCI)
 November 1 2011 Phase 1

자주 묻는 질문 (Frequently Asked Questions)

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

답변:
It can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as a clear solution for injection. And this compound in 15% Captisol at 8 mg/ml is a suspension for oral administration.