Dinaciclib (SCH727965)

Catalog No.S2768 Synonyms: PS-095760

Dinaciclib (SCH727965) Chemical Structure

Molecular Weight(MW): 396.49

Dinaciclib (SCH727965) 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. Phase 3.

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In DMSO USD 272 In stock
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5 Customer Reviews

  • (a) Western blot for RALB-GTP, total RALB and GAPDH proteins in KG1 AML cells treated for 8 h with DMSO or dinaciclib (representative of three independent experiments).

    Oncogene, 2017, 36(23):3263-3273. Dinaciclib (SCH727965) purchased from Selleck.

    Bcl-xL depleted (Bcl-xL shRNA) or non-target shRNA (NT) carrying LNZ308 and U87 cells were seeded at 60% confluence, allowed to attach overnight, and treated with indicated concentrations of dinaciclib for 24 h. Cytosolic (upper panel) and mitochondrial (lower panel) fractions were prepared, and equal amounts of protein were separated by SDS-PAGE and subjected to Western blotting analysis with the indicated antibodies. Lack of HSP70 in the cytosolic fraction clearly demonstrates that the cytoplasmic cytochrome c, AIF, or smac/DIABLO did not result from the mitochondrial damage during the extraction process.

    Mol Carcinog, 2018, 57(4):469-482. Dinaciclib (SCH727965) purchased from Selleck.

  • (B) Cells were treated with dinaciclib (25 nM) or placebo for 24 h and stained with fluorescent antibodies against DAPI (blue), cyclin B1 (red) and α-tubulin (green). Cyclin B1 level was significantly reduced after treatment of dinaciclib in prophase cells of BHP7-13, WRO82-1 and 8505C. (C) Cells were treated with dinaciclib (25 nM) or placebo for 24 h and stained with fluorescent antibodies against DAPI (blue), Aurora A (red) and α-tubulin (green). Aurora A level was significantly reduced after treatment of dinaciclib in BHP7-13, WRO82-1 and 8505C cells in prophase. Scale bar, 10 μm.

    PLoS One, 2017, 12(2):e0172315 . Dinaciclib (SCH727965) purchased from Selleck.

    CDK4/6 inhibition has potent cytostatic effect in HER2-positive models. The indicated cells were treated with PD-0332991 (1 uM) or Dinaciclib (1 uM) for 96 hours and plates were stained with crystal violet.

    Genes Cancer 2014 5(7-8), 261-72. Dinaciclib (SCH727965) purchased from Selleck.

  • It is a viability curve of various cell lines treated the dinaciclib.

    Dinaciclib (SCH727965) purchased from Selleck.

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Biological Activity

Description Dinaciclib (SCH727965) 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. 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

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 p27Kip1 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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CA46 M13peGFxd3C2b4Ppd{BCe3OjeR?= MlvwNVAxKG6P M4jvWFI1KGh? MVvpcoR2[2W|IHPlcIwh[3mlbHWgZZJz\XO2 M1K4VlI2Ojh7OEi3
Kasumi-1 M4DoT2Fxd3C2b4Ppd{BCe3OjeR?= NVHmNnBPOTByIH7N Ml;kNlQhcA>? NWGwfYlycW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=> NIOxWI0zPTJ6OUi4Oy=>
U937 NIDucFhHfW6ldHnvckBCe3OjeR?= NUDjdYZYOi93L{GwJI5O Mk\4N{Bp MknhZoxw[2u|IHnu[JVkfGmxbjDv[kBZSlBvMYOgZY5lKGSxd37zeJJm[W1idHHy[4V1ew>? NEfIR3YzPDN4MkS2OS=>
8226 NEHzUFJHfW6ldHnvckBCe3OjeR?= MmnaNk82NzFyIH7N NXPiT|FRPCCq MnLuZoxw[2u|IHnu[JVkfGmxbjDv[kBZSlBvMYOgZY5lKGSxd37zeJJm[W1idHHy[4V1ew>? NGXqdZgzPDN4MkS2OS=>
H929 MkTOSpVv[3Srb36gRZN{[Xl? MkP4Nk82NzFyIH7N M4TuTlQhcA>? MVnicI9kc3NiaX7keYN1cW:wIH;mJHhDWC1zczDhcoQh\G:5boP0doVidSC2YYLn[ZR{ Mke4NlQ{PjJ2NkW=
K562 NHnFVHpHfW6ldHnvckBCe3OjeR?= MYmxMlUwOy96IH7N M{LCRlYhcA>? MX\icI9kc3NiaX7keYN1cW:wIH;mJHhDWC1zczDhcoQh\G:5boP0doVidSC2YYLn[ZR{ MV6yOFM3OjR4NR?=
BaF3/Bcr-abl NYXoe|ZkTnWwY4Tpc44hSXO|YYm= NHy2d4MyNjVxMz:4JI5O MmnrOkBp MXTicI9kc3NiaX7keYN1cW:wIH;mJHhDWC1zczDhcoQh\G:5boP0doVidSC2YYLn[ZR{ MnfaNlQ{PjJ2NkW=
U937  MYPGeY5kfGmxbjDBd5NigQ>? M2jZUFIwOTBibl2= M3j6c|MhcA>? NUDp[2Nj[myxY3vzJIlv\HWldHnvckBw\iC[QmCtNZMh[W6mIHTve45{fHKnYX2geIFz\2W2cx?= Ml7oNlQ{PjJ2NkW=
1205Lu M3izbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFu4SVkyOC9|MDDuUS=> NYPONnIyPzJiaB?= NEfqdWpqdmirYnn0d{Bk\WyuIHfyc5d1cCCjbnSgd5Vzfmm4YXy= NVvlR|NlOjN3MkeyNlU>
WM1366 NW\ZeGdUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUexNE8{OCCwTR?= M4HwZ|czKGh? NHW0SnhqdmirYnn0d{Bk\WyuIHfyc5d1cCCjbnSgd5Vzfmm4YXy= NYW4WII6OjN3MkeyNlU>
RD NHvvNWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEPkTpZKSzVyPUiuNkBvVQ>? MmrTNlI{OTV{NEC=
Rh41 MnO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF7vdI1KSzVyPUGwMlUhdk1? MkPzNlI{OTV{NEC=
Rh18 NFv4Z2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFexWHJKSzVyPUGwMlUhdk1? MorpNlI{OTV{NEC=
Rh30 NF21WGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\sSXhKSzVyPUmgcm0> MX6yNlMyPTJ2MB?=
BT-12 MofXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVvJR|UxRThwNTDuUS=> NXvDbGk4OjJ|MUWyOFA>
CHLA-266 M1jLZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXLJR|UxRTdwMzDuUS=> M3OyOFIzOzF3MkSw
TC-71 M2n1cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHnSNWRKSzVyPUOuPUBvVQ>? NUjSZVZKOjJ|MUWyOFA>
CHLA-9 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF\KdphKSzVyPUigcm0> NXLPRohuOjJ|MUWyOFA>
CHLA-10 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlvZTWM2OD14LkOgcm0> M3L3ZlIzOzF3MkSw
CHLA-258 MlPXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWjEXXhJUUN3ME25Mlkhdk1? MlzwNlI{OTV{NEC=
GBM2 M4HhcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHvTWM2OD14LkWgcm0> MoeyNlI{OTV{NEC=
NB-1643 NHvhXmZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmrpTWM2OD1|LkOgcm0> MVSyNlMyPTJ2MB?=
NB-EBc1 NHvPPGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYTYXolNUUN3ME23JI5O NEj3XFIzOjNzNUK0NC=>
CHLA-90 Mm[4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWDC[YQ{UUN3ME23MlUhdk1? MV:yNlMyPTJ2MB?=
CHLA-136 NF;wdmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{O4VGlEPTB;OT64JI5O M2X0NlIzOzF3MkSw
NALM-6 NWXa[oc1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUfJR|UxRTRwNjDuUS=> MUeyNlMyPTJ2MB?=
COG-LL-317 NVL2PWZ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3rnUmlEPTB;Nj61JI5O M{DKVlIzOzF3MkSw
RS4;11 NYfUU5lZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTVwMTDuUS=> Mof4NlI{OTV{NEC=
MOLT-4 NHnqVHNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGq2SoVKSzVyPUmuN{BvVQ>? MojyNlI{OTV{NEC=
CCRF-CEM Mo\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH7vbI5KSzVyPUWuOkBvVQ>? M3exWFIzOzF3MkSw
Kasumi-1 Mn;zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{DoWmlEPTB;ND61JI5O Mmn4NlI{OTV{NEC=
Karpas-299 NIfjdXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV\JR|UxRTNwOTDuUS=> NIDGPGwzOjNzNUK0NC=>
Ramos-RA1 NIrBR4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mom0TWM2OD15Lkmgcm0> NHK5NVYzOjNzNUK0NC=>
MIAPaCa-2 NEjmdZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mly3O|IhcA>? NYTSTXpWT0l3ME2xNEBvVQ>? MmfTNlE4Pjh5N{m=
Pa20C  M1PoSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX\Xenh4PzJiaB?= MofKS2k2OD1{MDDuUS=> NUHYS4x{OjF5Nki3O|k>
ML-1 MVvBdI9xfG:|aYOgRZN{[Xl? MnzQNU0yODByIH7N NILWV4k1KGh? MWfpcoR2[2W|IHHwc5B1d3OrczDzcIlocHSueR?= Ml;5NlE4Pjh5N{e=

... Click to View More Cell Line Experimental Data

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]

Protocol

Kinase Assay:[1]
+ Expand

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 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.
Cell Research:[1]
+ Expand
  • Cell lines: A2780 cells
  • Concentrations: 0 μM -5 μM
  • Incubation Time: 24 hours
  • Method: 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 TopCounTM.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Nude mice bearing A2780 tumors
  • Formulation: 20% hydroxypropyl-β-cyclodextran
  • Dosages: 8 mg/kg, 16 mg/kg, 32 mg/kg, and 48 mg/kg
  • Administration: Administered via i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 26 mg/mL warmed (65.57 mM)
Ethanol 8 mg/mL warmed (20.17 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+ddH2O
For best results, use promptly after mixing.
10mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 396.49
Formula

C21H28N6O2

CAS No. 779353-01-4
Storage powder
in solvent
Synonyms PS-095760

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03484520 Recruiting Acute Myeloid Leukemia (AML) AbbVie|Merck Sharp & Dohme Corp. July 23 2018 Phase 1
NCT01676753 Recruiting Advanced or Metastatic Breast Cancer|Triple Negative Breast Cancer Jo Chien|Merck Sharp & Dohme Corp.|University of California San Francisco June 2016 Phase 1
NCT02684617 Recruiting rrCLL|rrMM|rrDLBCL Merck Sharp & Dohme Corp. March 29 2016 Phase 1
NCT01783171 Completed Pancreatic Adenocarcinoma|Recurrent Pancreatic Carcinoma|Stage III Pancreatic Cancer AJCC v6 and v7|Stage IV Pancreatic Cancer AJCC v6 and v7|Unresectable Pancreatic Carcinoma National Cancer Institute (NCI) January 15 2013 Phase 1
NCT01711528 Completed Recurrent Plasma Cell Myeloma National Cancer Institute (NCI) December 19 2012 Phase 1
NCT01650727 Completed Chronic Lymphocytic Leukemia|Small Lymphocytic Lymphoma Merck Sharp & Dohme Corp. October 2012 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

  • Question 1:

    I want to know how to reconstitute the inhibitor for in vivo studies?

  • Answer:

    S2768 (SCH727965) in 15% Captisol at 8 mg/ml is a suspension for oral administration. And it can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as a clear solution for injection.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID