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Purity: ≥98%
PD0166285 (PD-0166285) is a novel and potent 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 |
C26H27CL2N5O2
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| Molecular Weight |
512.43
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| CAS # |
185039-89-8
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| Related CAS # |
PD0166285 dihydrochloride;212391-63-4
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| SMILES |
ClC1C=CC=C(C=1C1=CC2=CN=C(NC3C=CC(=CC=3)OCCN(CC)CC)N=C2N(C)C1=O)Cl
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| InChi Key |
IFPPYSWJNWHOLQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H27Cl2N5O2/c1-4-33(5-2)13-14-35-19-11-9-18(10-12-19)30-26-29-16-17-15-20(25(34)32(3)24(17)31-26)23-21(27)7-6-8-22(23)28/h6-12,15-16H,4-5,13-14H2,1-3H3,(H,29,30,31)
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| Chemical Name |
6-(2,6-dichlorophenyl)-2-((4-(2-(diethylamino)ethoxy)phenyl)amino)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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 Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.88 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.17 mg/mL (4.23 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9515 mL | 9.7574 mL | 19.5149 mL | |
| 5 mM | 0.3903 mL | 1.9515 mL | 3.9030 mL | |
| 10 mM | 0.1951 mL | 0.9757 mL | 1.9515 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.
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