Dinaciclib

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.

CAS No. 779353-01-4

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 40800	国内在庫あり
5mg	JPY 25500	国内在庫あり
50mg	JPY 100500	国内在庫あり
200mg	JPY 250500	国内在庫あり
1g	JPY 598500	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（131）

製品安全説明書

現在のバッチを見る：純度： 99.99%

99.99

Dinaciclibと併用されることが多い化合物

Gemcitabine

Dinaciclib and Gemcitabine combination produces a more robust and sustained inhibition of tumor cell growth than either of the treatments alone.

Saqub H, et al. Sci Rep. 2020 Oct 28;10(1):18489.

Cisplatin

Dinaciclib and Cisplatin combination use decreases cell viability and sensitizes Ishikawa and HEC-1A cells to cisplatin treatment.

Howard D, et al. Cancers (Basel). 2021 Mar; 13(5): 1135.

MK-2206 2HCl

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

Hu C, et al. Mol Cancer Ther. 2015 Jul;14(7):1532-9.

SCH772984

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

Hayes TK, et al. Cancer Cell. 2016 Jan 11;29(1):75-89.

Vemurafenib (PLX4032)

Dinaciclib and Vemurafenib exhibit a synergistic anti-tumor effect in BRAF V600E-mutated melanoma cell lines, A2058/ M14.

Xu X, et al. Mol Cancer Ther. 2020 Feb; 19(2): 627–636.

Dinaciclib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
WM1366	Growth Inhibition Assay	10/30 nM	72 h	inhibits cell growth and survival	23527225
1205Lu	Growth Inhibition Assay	10/30 nM	72 h	inhibits cell growth and survival	23527225
U937	Function Assay	2/10 nM	3 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
K562	Function Assay	1.5/3/8 nM	6 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
8226	Function Assay	2/5/10 nM	4 h	blocks induction of XBP-1s and downstream targets	24362465
U937	Function Assay	2/5/10 nM	3 h	blocks induction of XBP-1s and downstream targets	24362465
Kasumi-1	Apoptosis Assay	100 nM	24 h	induces cell cycle arrest	25289887
CA46	Apoptosis Assay	100 nM	24 h	induces cell cycle arrest	25289887
ML-1	Apoptosis Assay	1-1000 nM	4 h	induces apoptosis slightly	21768777
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
Function assay	Sf9	10 uM		IC50 = 0.004 μM	29329658
MIAPaCa-2	Growth Inhibition Assay		72 h	GI50=10 nM	21768779
Pa20C	Growth Inhibition Assay		72 h	GI50=20 nM	21768779
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		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		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
Cytotoxicity assay	U2OS		96 hrs	IC50 = 0.006 μM	ChEMBL
Function assay	U2OS		1 hr	IC50 = 0.007 μM	ChEMBL
TC-71	Growth Inhibition Assay			IC50=3.9 nM	22315240
CHLA-266	Growth Inhibition Assay			IC50=7.3 nM	22315240
BT-12	Growth Inhibition Assay			IC50=8.5 nM	22315240
Rh30	Growth Inhibition Assay			IC50=9 nM	22315240
Rh18	Growth Inhibition Assay			IC50=10.5 nM	22315240
Rh41	Growth Inhibition Assay			IC50=10.5 nM	22315240
RD	Growth Inhibition Assay			IC50=8.2 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
Function assay	Sf9			IC50 = 0.072 μM	26741853
Function assay	sf9			IC50 = 0.002 μM	26851505
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

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.

Targets

CDK2 ^[1] (Cell-free assay)	CDK5 ^[1] (Cell-free assay)	CDK1 ^[1] (Cell-free assay)	CDK9 ^[1] (Cell-free assay)
1 nM	1 nM	3 nM	4 nM

In Vitro
In vitro	Dinaciclib is also a potent DNA replication inhibitor that blocks thymidine (dThd) DNA incorporation in A2780 cells with IC50 of 4 nM. Dinaciclib 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 Dinaciclib. Dinaciclib is active against a broad spectrum of human tumor cell lines. ^[1] Addition of Dinaciclib during hydroxyurea exposure also suppresses accumulation of γ-H2AX, in a dose-dependent manner. ^[2] Dinaciclib inhibits melanoma cell proliferation, and drives melanoma cells into massive apoptosis. ^[3] Dinaciclib induces the apoptosis of several osteosarcoma cell lines including those resistant to doxorubicin and dasatinib. Dinaciclib attenuates the phosphorylation of RNAP II at serine 2 and the phosphorylation of the CDK inhibitor p27^Kip1 at threonine 187. Reductions in phosphorylation activity occurrs at 12 - 40 nM Dinaciclib (4 to 16 hours post-Dinaciclib addition). Dinaciclib also reduces the phosphorylation of Rb at serine 807/811. Dinaciclib induces the apoptosis of mock- and p53-depleted U2OS cells to a similar extent. ^[4]
Kinase Assay	Cyclin/CDK kinase assay
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 Dinaciclib. 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.
細胞実験	細胞株	A2780 cells
	濃度	0 μM -5 μM
	反応時間	24 hours
	実験の流れ	A2780 cells are maintained in DMEM plus 10% fetal bovine serum and passaged twice weekly by detaching the monolayer with trypsin-EDTA. One hundred microliters of A2780 cells (5 × 10³ cells) are added per well to a 96-well Cytostar-T plate and incubated for 16 hours to 24 hours at 37 °C. Dinaciclib is serially diluted in complete media plus 2% ¹⁴C-labeled dThd. Media are removed from the Cytostar T plate; 200 μL of various Dinaciclib dilutions are added in quadruplicate; and the cells are incubated for 24 hours at 37 °C. Accumulated incorporation of radiolabel is assayed using scintillation proximity and measured on a TopCoun^TM.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	Cleaved PARP / c-Myc Mcl-1 / Bcl-2 / Bcl-xl / Bax / Bak / PUMA / Noxa RNAP II (P-Ser2/P-Ser5) Survivin		25289887
	Growth inhibition assay	Cell viability Cell viability		28361959
	Immunofluorescence	cyclin B1 / α-tubulin / Aurora A OCT4		28207834

In Vivo
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. Dinaciclib MED (minimum effective dose) appears to be <8 mg/kg. Dinaciclib is well tolerated, and the maximum body weight loss in the highest dosage group is 5%. Dinaciclib 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). Dinaciclib has a short plasma half-life in mouse. ^[1]
動物実験	動物モデル	Nude mice bearing A2780 tumors
	投与量	8 mg/kg, 16 mg/kg, 32 mg/kg, and 48 mg/kg
	投与経路	Administered via i.p.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
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

参考
[1] Parry D, et al. Mol Cancer Ther. 2010, 9(8), 2344-2453. [2] Guzi TJ, et al. Mol Cancer Ther. 2011, 10(4), 591-602. [3] Abdullah C, et al. Cell Cycle. 2011, 10(6), 977-988. [4] Fu W, et al. Mol Cancer Ther. 2011, 10(6), 1018-1027. + 展開

参考

[4] Fu W, et al. Mol Cancer Ther. 2011, 10(6), 1018-1027.

+ 展開

化学情報

分子量	396.49	化学式	C₂₁H₂₈N₆O₂
CAS No.	779353-01-4	SDF	Download Dinaciclib SDFをダウンロードする
Smiles	CCC1=C2N=C(C=C(N2N=C1)NCC3=C[N+](=CC=C3)[O-])N4CCCCC4CCO
保管	3年-20°C粉	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年-20°C粉	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:

DMSO : 79 mg/mL ( (199.24 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。)

Ethanol : 35 mg/mL

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):