Dinaciclib (SCH727965)

Catalog No.S2768

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.

Price Stock Quantity  
USD 272 In stock
USD 170 In stock
USD 470 In stock
USD 670 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Dinaciclib (SCH727965) Chemical Structure

Dinaciclib (SCH727965) Chemical Structure
Molecular Weight: 396.49

Validation & Quality Control

Customer Product Validation(2)

Quality Control & MSDS

Related Compound Libraries

Dinaciclib (SCH727965) is available in the following compound libraries:

CDK Inhibitors with Unique Features

  • Selective CDK Inhibitor

    BS-181 HCl CDK7-selective, IC50=21 nM. SNS-032 (BMS-387032) CDK2-selective, IC50=48 nM.

  • Most Potent CDK Inhibitor

    LY2835219 CDK4, IC50=2 nM; CDK6, IC50=10 nM.

  • CDK Inhibitor in Clinical Trial

    Palbociclib (PD0332991) Isethionate Phase III for Metastatic Breast Cancer.

  • Newest CDK Inhibitor

    NU6027 Potent ATR/CDK inhibitor, inhibits CDK1/2, ATR and DNA-PK with Ki of 2.5 μM/1.3 μM, 0.4 μM and 2.2 μM, enter cells more readily than the 6-aminopurine-based inhibitors.

Product Information

  • Compare CDK Inhibitors
    Compare CDK Products
  • Research Area

Product Description

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)
IC50 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
CA46M1vne2Fxd3C2b4Ppd{BCe3OjeR?=M1TLU|ExOCCwTR?=MmLxNlQhcA>?M4C4S4lv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S=NWGzUnU6OjV{OEm4PFc>
Kasumi-1NULUV2pSSXCxcITvd4l{KEG|c3H5MoDZNVAxKG6PNF20VoIzPCCqNXTMdpFVcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=>MVqyOVI5QTh6Nx?=
U937M{P0eGZ2dmO2aX;uJGF{e2G7NWPh[2tMOi93L{GwJI5OM{\iO|MhcA>?NEfBSINjdG:la4OgbY5lfWO2aX;uJI9nKFiEUD2xd{BidmRiZH;3cpN1emWjbTD0ZZJo\XS|M1z6VFI1OzZ{NE[1
8226NIfjWlVHfW6ldHnvckBCe3OjeR?=MkL3Nk82NzFyIH7NNXS0dG9TPCCqNYDqOYJx[myxY3vzJIlv\HWldHnvckBw\iC[QmCtNZMh[W6mIHTve45{fHKnYX2geIFz\2W2cx?=MoXhNlQ{PjJ2NkW=
H929NW[2SnpDTnWwY4Tpc44hSXO|YYm=NVPPeXZoOi93L{GwJI5OMnrHOEBpNHXUOXZjdG:la4OgbY5lfWO2aX;uJI9nKFiEUD2xd{BidmRiZH;3cpN1emWjbTD0ZZJo\XS|NWXJN3ZpOjR|NkK0OlU>
K562NV3D[lhCTnWwY4Tpc44hSXO|YYm=MmDUNU42NzNxODDuUS=>MUG2JIg>NGHYdnRjdG:la4OgbY5lfWO2aX;uJI9nKFiEUD2xd{BidmRiZH;3cpN1emWjbTD0ZZJo\XS|MV2yOFM3OjR4NR?=
BaF3/Bcr-ablMVHGeY5kfGmxbjDBd5NigQ>?MnGxNU42NzNxODDuUS=>NH:3OpE3KGh?M1jST4Jtd2OtczDpcoR2[3Srb36gc4YhYEKSLUHzJIFv\CCmb4fud5Rz\WGvIIThdodmfHN?MUKyOFM3OjR4NR?=
U937 NXS3WYdNTnWwY4Tpc44hSXO|YYm=MXGyM|ExKG6PM3L6cVMhcA>?NITJ[WpjdG:la4OgbY5lfWO2aX;uJI9nKFiEUD2xd{BidmRiZH;3cpN1emWjbTD0ZZJo\XS|NVLjfZdoOjR|NkK0OlU>
1205LuM{DOTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MkWyNVAwOzBibl2=MnvGO|IhcA>?MX;pcohq[mm2czDj[YxtKGe{b4f0bEBidmRic4Xyeol3[Wx?MlLkNlM2Ojd{MkW=
WM1366MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NXfG[|NCOTBxM{Cgcm0>NH71NXI4OiCqMofxbY5pcWKrdIOgZ4VtdCCpcn;3eIgh[W6mIIP1dpZqfmGuMom2NlM2Ojd{MkW=
RDMXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHHwNldKSzVyPUiuNkBvVQ>?M2D2W|IzOzF3MkSw
Rh41NFXRU4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmTLTWM2OD1zMD61JI5OM4XnV|IzOzF3MkSw
Rh18NUKzfZRrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIrFdWNKSzVyPUGwMlUhdk1?Mo\oNlI{OTV{NEC=
Rh30MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NXX2bYxwUUN3ME25JI5OM3zBflIzOzF3MkSw
BT-12MoHIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MmfuTWM2OD16LkWgcm0>MUeyNlMyPTJ2MB?=
CHLA-266NXzTd21MT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWq5NHdqUUN3ME23MlMhdk1?M1mzO|IzOzF3MkSw
TC-71M372dGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NH\XNmpKSzVyPUOuPUBvVQ>?Mme3NlI{OTV{NEC=
CHLA-9NIPhOXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NHrmSItKSzVyPUigcm0>NV3aXJRmOjJ|MUWyOFA>
CHLA-10MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1PiZWlEPTB;Nj6zJI5ONXzacmVWOjJ|MUWyOFA>
CHLA-258MmrIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGjPfGFKSzVyPUmuPUBvVQ>?MmrLNlI{OTV{NEC=
GBM2MkntS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4na[mlEPTB;Nj61JI5ONF3zV2YzOjNzNUK0NC=>
NB-1643NUXSbYZrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHT0UXFKSzVyPUOuN{BvVQ>?MkG4NlI{OTV{NEC=
NB-EBc1NV7SfFhlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Mn3LTWM2OD15IH7NNHn6UZAzOjNzNUK0NC=>
CHLA-90M3;McWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXTJR|UxRTdwNTDuUS=>MmK1NlI{OTV{NEC=
CHLA-136NHW0ZnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NICweWxKSzVyPUmuPEBvVQ>?M1jJclIzOzF3MkSw
NALM-6MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NInzRlZKSzVyPUSuOkBvVQ>?MnTXNlI{OTV{NEC=
COG-LL-317Mn61S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NF3ReZpKSzVyPU[uOUBvVQ>?M3H4VVIzOzF3MkSw
RS4;11M1nYdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MmfjTWM2OD13LkGgcm0>NXjr[29sOjJ|MUWyOFA>
MOLT-4MmnpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYPJR|UxRTlwMzDuUS=>MkDCNlI{OTV{NEC=
CCRF-CEMM1;WUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MUDJR|UxRTVwNjDuUS=>NUHZTYhYOjJ|MUWyOFA>
Kasumi-1M3njUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MX;JR|UxRTRwNTDuUS=>NFfpVZozOjNzNUK0NC=>
Karpas-299MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MnewTWM2OD1|Lkmgcm0>M1PXcVIzOzF3MkSw
Ramos-RA1NFHUWYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NH64SVVKSzVyPUeuPUBvVQ>?M3\Md|IzOzF3MkSw
MIAPaCa-2M2jYWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MoL6O|IhcA>?NID0fWRIUTVyPUGwJI5OM4TtWVIyPzZ6N{e5
Pa20C MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVO3NkBpNVLsTodIT0l3ME2yNEBvVQ>?MYSyNVc3QDd5OR?=
ML-1M1Xic2Fxd3C2b4Ppd{BCe3OjeR?=NUjFblBQOS1zMECwJI5ONGDLO481KGh?NI[0bG9qdmS3Y3XzJIFxd3C2b4Ppd{B{dGmpaITsfS=>NYLmdYVuOjF5Nki3O|c>

... 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]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

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 Assay: [1]

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.

Animal Study: [1]

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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[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.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-05-07)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02684617 Recruiting rrCLL|rrMM|rrDLBCL Merck Sharp & Dohme Corp. March 2016 Phase 1
NCT01783171 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 Suspended 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  ...more 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

view more

Chemical Information

Download Dinaciclib (SCH727965) SDF
Molecular Weight (MW) 396.49
Formula

C21H28N6O2

CAS No. 779353-01-4
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms PS-095760
Solubility (25°C) * In vitro DMSO 26 mg/mL warmed (65.57 mM)
Ethanol 8 mg/mL warmed (20.17 mM)
Water <1 mg/mL (<1 mM)
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 Name (2S)​-1-​[3-​ethyl-​7-​[[(1-​oxido-​3-​pyridinyl)​methyl]​amino]​pyrazolo[1,​5-​a]​pyrimidin-​5-​yl]​-2-​piperidineethanol

Customer Product Validation (2)


Click to enlarge
Rating
Source Genes Cancer 2014 5(7-8), 261-72. Dinaciclib (SCH727965) purchased from Selleck
Method Crystal violet
Cell Lines MCF10A/Her2 cells
Concentrations 1 uM
Incubation Time 96 h
Results The RB-deficient populations proceeded to proliferate in the presence of PD-0332991. Importantly, this phenomenon was specific to CDK4/6 inhibitors, and the PAN-CDK inhibitor Dinaciclib killed all cells irrespective of the presence of RB.

Click to enlarge
Rating
Source Dinaciclib (SCH727965) purchased from Selleck
Method
Cell Lines MEC1/3T3/Riva/OCI-ly8
Concentrations 0-50 nM
Incubation Time 24 h
Results

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.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related CDK Products

  • SU9516

    SU 9516 is a 3-substituted indolinone CDK inhibitor with IC50 of 22 nM, 40 nM, and 200 nM for CDK2, CDK1, and CDK4, respectively.

  • Ro-3306

    RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with Ki of 20 nM, >15-fold selectivity against a diverse panel of human kinases.

  • Purvalanol A

    Purvalanol A is a potent, and cell-permeable CDK inhibitor with IC50 of 4 nM, 70 nM, 35 nM, and 850 nM for cdc2-cyclin B, cdk2-cyclin A, cdk2-cyclin E, and cdk4-cyclin D1, respectively.

  • Palbociclib (PD-0332991) HCl

    Palbociclib (PD-0332991) HCl is a highly selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM in cell-free assays, respectively. It shows no activity against CDK1/2/5, EGFR, FGFR, PDGFR, InsR, etc. Phase 3.

    Features:Non-cytotoxic, and halts cancer cell growth & could be used in glioblastoma that has relapsed after temozolomide treatment (a chemotherapeutic used to treat many cancers).

  • Palbociclib (PD0332991) Isethionate

    Palbociclib (PD0332991) Isethionate is a highly selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM in cell-free assays. It shows no activity against CDK1/2/5, EGFR, FGFR, PDGFR, InsR, etc. Phase 3.

    Features:The 1st specific inhibitor for CDK4/6 to show promise in multiple cancers.

  • Flavopiridol (Alvocidib) HCl

    Flavopiridol HCl competes with ATP to inhibit CDKs including CDK1, CDK2, CDK4 and CDK6 with IC50 of ~ 40 nM in cell-free assays. It is 7.5-fold more selective for CDK1/2/4/6 than CDK7. Flavopiridol is initially found to inhibit EGFR and PKA. Phase 1/2.

  • Roscovitine (Seliciclib,CYC202)

    Roscovitine (Seliciclib, CYC202) is a potent and selective CDK inhibitor for Cdc2, CDK2 and CDK5 with IC50 of 0.65 μM, 0.7 μM and 0.16 μM in cell-free assays. It shows little effect on CDK4/6. Phase 2.

  • LY2835219

    LY2835219 is a potent and selective inhibitor of CDK4 and CDK6 with IC50 of 2 nM and 10 nM in cell-free assays, respectively. Phase 3.

  • Ribociclib (LEE011)

    Ribociclib (LEE011) is an orally available, and highly specific CDK4/6 inhibitor. Phase 3.

  • SNS-032 (BMS-387032)

    SNS-032 (BMS-387032) has firstly been described as a selective inhibitor of CDK2 with IC50 of 48 nM in cell-free assays and is 10- and 20-fold selective over CDK1/CDK4. It is also found to be sensitive to CDK7/9 with IC50 of 62 nM/4 nM, with little effect on CDK6. Phase 1.

Recently Viewed Items

Tags: buy Dinaciclib (SCH727965) | Dinaciclib (SCH727965) supplier | purchase Dinaciclib (SCH727965) | Dinaciclib (SCH727965) cost | Dinaciclib (SCH727965) manufacturer | order Dinaciclib (SCH727965) | Dinaciclib (SCH727965) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us