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250mg |
PD-166285 diHCl (PD0166285 dihydrochloride) is a novel Wee1 and Chk1 inhibitor with anticancer activity and enzymatic activity at nanomolar concentrations (IC50s of 24 and 72 nM for WEE1 and Myt1, respectively). PD0166285 is a novel G2 checkpoint abrogator. This G2 checkpoint abrogation by PD0166285 was demonstrated to kill cancer cells, there at a toxic highest dose of 0.5 muM in some cell lines for exposure periods of no longer than 6 hours. The deregulated cell cycle progression may have ultimately damaged the cancer cells. We herein report one of the mechanism by which PD0166285 leads to cell death in the B16 mouse melanoma cell line.
ln Vitro |
In seven out of seven cancer cell lines, PD0166285 (0.5 μM) significantly suppresses irradiation-induced Cdc2 phosphorylation at the Tyr-15 and Thr-14[1]. In p53 mutant HT29 cells and the E6-transfected, p53-null ovarian cancer cell line PA-1, PD0166285 sensitizes radiation-induced cell killing; however, in p53 wild-type PA-1 cells, this effect is less pronounced. Radiation-induced G2 arrest is reversed by PD0166285 and mitotic cell populations are markedly increased[1]. PD0166285 has a sensitivity enhancement ratio of 1.23 and functions as a radiosensitizer to make cells more sensitive to radiation-induced cell death[1].
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Cell Assay |
Western Blot Analysis[1]
Cell Types: Human and mouse cancer cell lines (HCT116, HT29, DLD-1, HCT8, H460, HeLa, C 26 ). Tested Concentrations: 0.5 μM. Incubation Duration: 4 h. Experimental Results: Inhibited Cdc2Y15 and CdcT14 phosphorylation. |
Animal Protocol |
Animal/Disease Models: Wild-type, Abcg2-/-, Abcb1a/b-/- and Abcb1a/b;Abcg2-/- FVB mice[2].
Doses: 5 mg/kg. Route of Administration: IV. Experimental Results: Cmax is about 400 ng/mL. P-gp, but not BCRP, limited the brain penetration of PD0166285. |
References |
[1]. Wang Y, et al. Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator. Cancer Res. 2001 Nov 15;61(22):8211-7.
[2]. Mark C de Gooijer, et al. ATP-binding cassette transporters limit the brain penetration of Wee1 inhibitors. Invest New Drugs. 2018 Jun;36(3):380-387. |
Molecular Formula |
C26H28CL3N5O2
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Molecular Weight |
548.8918
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CAS # |
212391-63-4
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Related CAS # |
PD0166285;185039-89-8
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SMILES |
ClC1C([H])=C([H])C([H])=C(C=1C1=C([H])C2=C([H])N=C(N([H])C3C([H])=C([H])C(=C([H])C=3[H])OC([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])N=C2N(C([H])([H])[H])C1=O)Cl.Cl[H]
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.8219 mL | 9.1093 mL | 18.2186 mL | |
5 mM | 0.3644 mL | 1.8219 mL | 3.6437 mL | |
10 mM | 0.1822 mL | 0.9109 mL | 1.8219 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.