PD0166285

SKU: orb1300335

Description

PD0166285 is a potent, nanomolar-range inhibitor of the Wee1 and Chk1 kinases, effectively abrogating the G2/M cell cycle checkpoint. This small molecule is utilized in cancer research to sensitize tumor cells to DNA-damaging agents in both in vitro and in vivo experimental models.

Research Area

Cell Biology

Key Properties

• CAS Number: 185039-89-8
• MW: 512.43
• Purity: 99.59% (May vary between batches)
• Formula: C₂₆H₂₇Cl₂N₅O₂
• SMILES: CCN(CC)CCOc1ccc(Nc2ncc3cc(-c4c(Cl)cccc4Cl)c(=O)n(C)c3n2)cc1
• Target: Apoptosis,Chk,Wee1
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:93 mg/mL (181.49 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (6.44 mM);Ethanol:93 mg/mL (181.49 mM)

Bioactivity

• Target IC50:
  Chk1:3.4 μM|Myt1:72 nM|Wee1:24 nM
• In Vivo:
  PD0166285 at 0.5 μM concentration can inhibit Cdc2Y15 /T14 phosphorylation in all cell lines tested, regardless of their p53 status and pharmacological targeting of WEE1 by PD0166285 sensitizes U251-FM GBM tumors to IR in vivo.
• In Vitro:
  PD0166285 is identified to inhibit Wee1 activity at nanomolar concentrations. The inhibitor abrogates G2/M checkpoint inducing early cell division. At the cellular level, 0.5 μM PD0166285 dramatically inhibits irradiation-induced Cdc2 phosphorylation at the Tyr-15 and Thr-14 in seven of seven cancer cell lines tested. This G2 checkpoint abrogation by PD0166285 is demonstrated to kill cancer cells. PD0166285 does not inhibit Cdc2/cyclin B but inhibits Chk1 kinase at a much higher concentration (3433 nM). the treatment of cells with the inhibitor is related to microtubule stabilization and decrease in cyclin D transcription. Thus, PD0166285 may be a potentially useful anti-cancer therapy.
• Cell Research:
  B16 cells (1 × 105 cells in 100 mm-dishes) are maintained in medium overnight. In addition, the cells are treated with (0, 0.5, 1.0, or 2.0 μM) PD0166285 (including DMSO vehicle) for indicated times. The cells are washed twice with phosphate-buffered saline (PBS). Next, the cells are trypsinized, so the cell numbers in each dish are determined by using a computed cell-counter (Sysmex CDA-500) according to manufacturer's recommendation. (Only for Reference)
• Animal Research:
  E98 tumor fragments (8 mm3) were grafted subcutaneously in the flank of Balb/C nude mice (n = 10). For the experiments with the orthotopic tumors, U251 mg and E98 cells were transduced to express Fluc and mCherry, to generate U251-FM and E98-FM cells. One million cells were injected intracranially. Starting at 12 days after tumor inoculation, mice received the WEE1 inhibitor PD0166285 via intraperitoneal injections (500 μl of a 20 μM solution diluted in NaCl) or vehicle for 5 consecutive days. On days 10–15, mice were irradiated with a single dose of irradiation.

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

PD166285, PD-166285, PD 166285, PD 0166285, PD0166285, PD-0166285, inhibit, Myt1, Inhibitor, Apoptosis, Chk1, Wee1

Compound Identifiers

PubChem CID

5311382