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.

Size Price Stock Quantity  
In DMSO USD 272 In stock
USD 170 In stock
USD 470 In stock
USD 670 In stock

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2 Customer Reviews

  • 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.

Purity & Quality Control

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

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 MkLzRZBweHSxc3nzJGF{e2G7 NXnyc|BsOTByIH7N NHTtfG4zPCCq M1TGRYlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S= NGDSfIgzPTJ6OUi4Oy=>
Kasumi-1 MU\BdI9xfG:|aYOgRZN{[Xl? MWGxNFAhdk1? MVeyOEBp NILQSYhqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0 MV2yOVI5QTh6Nx?=
U937 MYTGeY5kfGmxbjDBd5NigQ>? NHrYPIwzNzVxMUCgcm0> NHz6U3o{KGh? MnW5Zoxw[2u|IHnu[JVkfGmxbjDv[kBZSlBvMYOgZY5lKGSxd37zeJJm[W1idHHy[4V1ew>? NUW2NJI2OjR|NkK0OlU>
8226 MkjuSpVv[3Srb36gRZN{[Xl? NILHUJIzNzVxMUCgcm0> NYPkc2ZFPCCq MYXicI9kc3NiaX7keYN1cW:wIH;mJHhDWC1zczDhcoQh\G:5boP0doVidSC2YYLn[ZR{ NFLlZ40zPDN4MkS2OS=>
H929 MnLWSpVv[3Srb36gRZN{[Xl? MWKyM|UwOTBibl2= M1q0[lQhcA>? NXLPbmdG[myxY3vzJIlv\HWldHnvckBw\iC[QmCtNZMh[W6mIHTve45{fHKnYX2geIFz\2W2cx?= MV:yOFM3OjR4NR?=
K562 NF74cIJHfW6ldHnvckBCe3OjeR?= NWj6PVBLOS53L{OvPEBvVQ>? NFL1WZI3KGh? M4XPOoJtd2OtczDpcoR2[3Srb36gc4YhYEKSLUHzJIFv\CCmb4fud5Rz\WGvIIThdodmfHN? MlrlNlQ{PjJ2NkW=
BaF3/Bcr-abl MkDDSpVv[3Srb36gRZN{[Xl? MnP6NU42NzNxODDuUS=> NYH3bHJiPiCq MUHicI9kc3NiaX7keYN1cW:wIH;mJHhDWC1zczDhcoQh\G:5boP0doVidSC2YYLn[ZR{ M2XtN|I1OzZ{NE[1
U937  M1rn[2Z2dmO2aX;uJGF{e2G7 NX\nUZlKOi9zMDDuUS=> M1HnTFMhcA>? Mmm5Zoxw[2u|IHnu[JVkfGmxbjDv[kBZSlBvMYOgZY5lKGSxd37zeJJm[W1idHHy[4V1ew>? M4S4RlI1OzZ{NE[1
1205Lu NGrv[Y5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV24T4dVOTBxM{Cgcm0> MYW3NkBp MojMbY5pcWKrdIOgZ4VtdCCpcn;3eIgh[W6mIIP1dpZqfmGu NF7aZlIzOzV{N{KyOS=>
WM1366 NGfncldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXiwNXZTOTBxM{Cgcm0> NUS3NY1{PzJiaB?= M3\SeYlvcGmkaYTzJINmdGxiZ4Lve5RpKGGwZDDzeZJ3cX[jbB?= MmXMNlM2Ojd{MkW=
RD M13NV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVy3d|k1UUN3ME24MlIhdk1? NYG1cYNvOjJ|MUWyOFA>
Rh41 NXPnWlA6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrZWIp{UUN3ME2xNE42KG6P NYLHTGVNOjJ|MUWyOFA>
Rh18 MoTZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjEU2pKSzVyPUGwMlUhdk1? M3e2[FIzOzF3MkSw
Rh30 MnnwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2PMVGlEPTB;OTDuUS=> M2T4XVIzOzF3MkSw
BT-12 MlnLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUDJR|UxRThwNTDuUS=> M4GzVFIzOzF3MkSw
CHLA-266 NUDmeZA2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEDhSo5KSzVyPUeuN{BvVQ>? NX:xe3p{OjJ|MUWyOFA>
TC-71 NWTLOlRKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjObpVyUUN3ME2zMlkhdk1? MYeyNlMyPTJ2MB?=
CHLA-9 NYP3eYZpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGnGNppKSzVyPUigcm0> NVnLUlRIOjJ|MUWyOFA>
CHLA-10 NGn0WplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTZwMzDuUS=> M4P5blIzOzF3MkSw
CHLA-258 NUS4UoRDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTlwOTDuUS=> NI\EdGYzOjNzNUK0NC=>
GBM2 MmT0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PRfWlEPTB;Nj61JI5O NF3Fc28zOjNzNUK0NC=>
NB-1643 NV70eYl6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTNwMzDuUS=> NHrpOFUzOjNzNUK0NC=>
NB-EBc1 NX71emtzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYGwfFBbUUN3ME23JI5O MnfXNlI{OTV{NEC=
CHLA-90 NH;5RY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYrJR|UxRTdwNTDuUS=> MYqyNlMyPTJ2MB?=
CHLA-136 MlHuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2f4WmlEPTB;OT64JI5O MnPFNlI{OTV{NEC=
NALM-6 M2TKZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkTETWM2OD12Lk[gcm0> Mn\ZNlI{OTV{NEC=
COG-LL-317 M2Lofmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3rqNGlEPTB;Nj61JI5O M1fjSlIzOzF3MkSw
RS4;11 MnnQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHfRblhKSzVyPUWuNUBvVQ>? M3vWWVIzOzF3MkSw
MOLT-4 Mn;6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1TJeGlEPTB;OT6zJI5O MonuNlI{OTV{NEC=
CCRF-CEM NXLkcYFQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHnoNY9KSzVyPUWuOkBvVQ>? MV[yNlMyPTJ2MB?=
Kasumi-1 NFzTe2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M13TcWlEPTB;ND61JI5O MmX0NlI{OTV{NEC=
Karpas-299 MkTjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzLZ21GUUN3ME2zMlkhdk1? NIK2TJQzOjNzNUK0NC=>
Ramos-RA1 MmLDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVSwO2hmUUN3ME23Mlkhdk1? M1v2XFIzOzF3MkSw
MIAPaCa-2 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2LuOFczKGh? MkLlS2k2OD1zMDDuUS=> M1zSbVIyPzZ6N{e5
Pa20C  M2XYNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYnDTZR[PzJiaB?= MWfHTVUxRTJyIH7N MlfjNlE4Pjh5N{m=
ML-1 M4XVNGFxd3C2b4Ppd{BCe3OjeR?= MnjYNU0yODByIH7N NWHpWXVHPCCq M{XLZ4lv\HWlZYOgZZBweHSxc3nzJJNtcWeqdHz5 MmSwNlE4Pjh5N{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 (65.57 mM) warming
Ethanol 8 mg/mL warmed (20.17 mM)
Water <1 mg/mL
In vivo 2% DMSO+30% PEG 300+ddH2O 10mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* 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
NCT01676753 Active, not 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|Phase 2
NCT02684617 Recruiting rrCLL|rrMM|rrDLBCL Merck Sharp & Dohme Corp. March 2016 Phase 1
NCT01783171 Active, not recruiting Pancreatic Adenocarcinoma|Recurrent Pancreatic Carcinoma|Stage III Pancreatic Cancer|Stage IV Pancreatic Cancer|Unresectable Pancreatic Carcinoma National Cancer Institute (NCI) January 2013 Phase 1
NCT01711528 Active, not recruiting Recurrent Plasma Cell Myeloma National Cancer Institute (NCI) December 2012 Phase 1
NCT01650727 Completed Chronic Lymphocytic Leukemia|Small Lymphocytic Lymphoma Merck Sharp & Dohme Corp. October 2012 Phase 1
NCT01624441 Active, not recruiting Estrogen Receptor Negative|HER2/Neu Negative|Male Breast Carcinoma|Progesterone Receptor Negative|Recurrent Breast Carcinoma|Stage IV Breast Cancer|Triple-Negative Breast Carcinoma National Cancer Institute (NCI) August 2012 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID