Dinaciclib

SKU: orb1307130

Description

Dinaciclib (SCH 727965) is a potent and selective inhibitor of CDK1, CDK2, CDK5, and CDK9 with antitumor activity. It has been investigated in vitro and in vivo for oncology research, particularly in studies of cell cycle arrest and transcription inhibition in various cancer models.

Research Area

Cell Biology

Key Properties

• CAS Number: 779353-01-4
• MW: 396.49
• Purity: 99.75%
• Formula: C₂₁H₂₈N₆O₂
• SMILES: N(CC1=CN(=O)=CC=C1)C=2N3C(N=C(C2)N4[C@H](CCO)CCCC4)=C(CC)C=N3
• Target: Apoptosis,CDK
• Solubility: DMSO:130 mg/mL (327.88 mM);Ethanol:8 mg/mL (20.18 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (12.61 mM)

Bioactivity

• Target IC50:
  CDK5:1 nM (cell free)|CDK1:3 nM (cell free)|CDK9:4 nM (cell free)|CDK2:1 nM (cell free)
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Dinaciclib (40 mg/kg, 20% (w/v) HPBCD) was injected intraperitoneally twice weekly for four weeks into CD1 nu/nu athymic mice harboring human pancreatic cancer tumors, JH033 or Panc286. RESULTS: Dinaciclib inhibited the in vivo growth of a group of hypo-permeable cancer xenografts. METHODS: To assay antitumor activity in vivo, Dinaciclib (8-48 mg/kg) was injected intraperitoneally into BALB/c mice harboring ovarian cancer tumor A2780 once daily for ten days. RESULTS: Dinaciclib had dose-dependent antitumor activity in vivo and almost completely inhibited tumor growth at dose levels below MTD.
• In Vitro:
  METHODS: Human pancreatic cancer cell lines MIAPaCa-2 and Pa20C were treated with Dinaciclib (0.5-128 nM) for 72 h. Cell viability was assayed using MTT Assay. RESULTS: Dinaciclib inhibited the growth of MIAPaCa-2 and Pa20C cells in a dose-dependent manner, with a GI50 of approximately 10 and 20 nM, respectively. METHODS: Human osteosarcoma cell lines SaOs-2 and U2OS were treated with Dinaciclib (5-62 nmol/L) for 4-24 h, and the expression levels of target proteins were detected using Western Blot. RESULTS: Dinaciclib eliminated the phosphorylation of CDK substrates in osteosarcoma cells.
• Cell Research:
  A2780 cells were plated into six-well tissue culture dishes and allowed to adhere. Cells were then exposed to differing concentrations of SCH 727965 or a DMSO control vehicle for 24 hours, followed by a brief (30 min) pulsed exposure to bromodeoxyuridine (BrdUrd). Cells were then harvested, immunostained using FITC-conjugated antibodies specific for BrdUrd, counter-stained with propidium iodide/RNase A solution, and analyzed using flow cytometry. Fluorescence-activated cell sorting analyses were done on a FACSCalibur instrument. FITC-positive BrdUrd staining and propidium iodide signal allowed assessment of ongoing DNA replication and the cell cycle stage. Percentages of the cell population in each cell cycle stage were plotted for each test article concentration .
• Animal Research:
  For tumor implantation, specific cell lines were grown in vitro, washed once with PBS, and resuspended in 50% Matrigel in PBS to a final concentration of 4 × 10^7 to 5 × 10^7 cells per milliliter. Nude mice were injected with 0.1 mL of this suspension s.c. in the flank region. Tumor length (L), width (W), and height (H) were measured by a caliper twice weekly on each mouse and then used to calculate tumor volume using the formula (L × W × H)/2. When the tumor volume reached ～100 mm^3, the animals were randomized to treatment groups (10 mice/group) and treated i.p. with either SCH 727965 or individual chemotherapeutic agents according to the dosing schedule indicated in table and figure legends. Tumor volumes and body weights were measured during and after the treatment periods. Data were expressed as means ± SEM. Animals were euthanized according to the Institutional Animal Care and Use Committee guidelines .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Dinaciclib, Cyclin dependent kinase, CDK5, CDK9, CDK, CDK1, CDK2, Apoptosis, inhibit, Inhibitor, SCH727965, SCH-727965, SCH 727965, PS095760, PS-095760, PS 095760

Quick Database Links

Gene Symbol

Apoptosis,CDK