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SCH727965

Cat. No. M1807
SCH727965 Structure
Synonym:

Dinaciclib

Size Price Availability Quantity
5mg USD 125 In stock
10mg USD 175 In stock
50mg USD 490 In stock
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Quality Control
Biological Activity

SCH727965 (Dinaciclib) is a novel small molecule multi-CDK inhibitor with low nanomolar potency against CDK1, CDK2, CDK5 and CDK9 that has shown favorable toxicity and efficacy in preliminary mouse experiments, and has been well tolerated in Phase I clinical trials. Cyclin-dependent kinases (CDK) are key positive regulators of cell cycle progression and attractive targets in oncology. SCH727965 was selected as a clinical candidate using a functional screen in vivo that integrated both efficacy and safety parameters. Compared with flavopiridol, SCH727965 exhibits superior activity with an improved therapeutic index. In cell-based assays, SCH727965 completely suppressed retinoblastoma phosphorylation, which correlated with apoptosis onset and total inhibition of bromodeoxyuridine incorporation in >100 tumor cell lines of diverse origin and background. Moreover, short exposures to SCH727965 were sufficient for long-lasting cellular effects. SCH727965 induced regression of established solid tumors in a range of mouse models following intermittent scheduling of doses below the maximally tolerated level. These results suggest that SCH727965 is a potent and selective CDK inhibitor and a novel cytotoxic agent.

Protocol
Cell Experiment
Cell lines A2780 cells
Preparation method dThd uptake growth inhibition assay.
A2780 cells were maintained in DMEM (Cellgro) plus 10% fetal bovine serum (HyClone) and passaged twice weekly by detaching the monolayer with trypsin-EDTA (Life Technologies). One hundred microliters of A2780 cells (5 × 103 cells) were added per well to a 96-well Cytostar-T plate (Amersham) and incubated for 16 to 24 hours at 37°C. Compounds were serially diluted in complete media plus 2% 14C-labeled dThd (Amersham). Media were removed from the Cytostar T plate; 200 μL of various compound dilutions were added in quadruplicate; and the cells were incubated for 24 hours at 37°C. Accumulated incorporation of radiolabel was assayed using scintillation proximity and measured on a TopCount (Packard/Perkin-Elmer Life Sciences). The percentage of dThd uptake inhibition, relative to a vehicle control, was calculated and plotted on log-linear plots to allow derivation of IC50 values.
Concentrations 0~500nM
Incubation time 16 to 24 h
Animal Experiment
Animal models A2780 cells xenograft model in mice
Formulation 20% hydroxypropyl-β-cyclodextran
Dosages 8, 16, 32, and 48 mg/kg daily for 10 d
Administration i.p.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
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.

Chemical Information
Molecular Weight 396.48
Formula C21H28N6O2
CAS Number 779353-01-4
Purity >99.0%
Solubility DMSO ≥76 mg/mL
Storage at -20°C
Customer Product Validations & Biological Datas
Source Mol Cancer Ther (2014). Figure 2. SCH727965
Method Western blot
Cell Lines U937 cells
Concentrations 2 nmol/L
Incubation Time 3 h
Results As shown in Fig. 2A, exposure to SCH727965 failed to block XBP-1s mRNA induction in multiple thapsigargin-treated leukemia and myeloma cell lines, for example, U937, K562, 8226, and BaF3/T315I.
Rating
Source Mol Cancer Ther (2014). Figure 1. SCH727965
Method Western blot
Cell Lines U937 cells
Concentrations 2 nmol/L
Incubation Time 16 h
Results SCH727965-mediated reductions in XBP-1s and Grp78 expression were also observed in U937 cells exposed to another ER stress inducer, tunicamycin
Rating
References

The novel cyclin-dependent kinase inhibitor dinaciclib (SCH727965) promotes apoptosis and abrogates microenvironmental cytokine protection in chronic lymphocytic leukemia cells.
Johnson et al. Leukemia. 2012 May 30. PMID: 22791353.

The cyclin-dependent kinase inhibitor SCH 727965 (dinacliclib) induces the apoptosis of osteosarcoma cells.
Fu et al. Mol Cancer Ther. 2011 Jun;10(6):1018-27. PMID: 21490307.

Dinaciclib (SCH 727965), a novel and potent cyclin-dependent kinase inhibitor.
Parry D, et al. Mol Cancer Ther. 2010 Aug;9(8):2344-53. PMID: 20663931.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: SCH727965, Dinaciclib supplier, CDK, inhibitors

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