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MedKoo Cat#: 406345 | Name: PD0166285
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PD0166285 is a potent Wee1 inhibitor and Chk1 inhibitor with activity at nanomolar concentrations. 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. PD0166285 showed a relatively good anti-leukemia effect

Chemical Structure

PD0166285
PD0166285
CAS#185039-89-8 (free base)

Theoretical Analysis

MedKoo Cat#: 406345

Name: PD0166285

CAS#: 185039-89-8 (free base)

Chemical Formula: C26H27Cl2N5O2

Exact Mass: 511.1542

Molecular Weight: 512.43

Elemental Analysis: C, 60.94; H, 5.31; Cl, 13.84; N, 13.67; O, 6.24

Price and Availability

Size Price Availability Quantity
5mg USD 110.00 Ready to ship
10mg USD 190.00 Ready to ship
25mg USD 350.00 Ready to ship
50mg USD 550.00 Ready to ship
100mg USD 950.00 Ready to ship
200mg USD 1,650.00 Ready to ship
500mg USD 2,650.00 Ready to ship
1g USD 3,750.00 Ready to ship
2g USD 6,450.00 2 Weeks
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Related CAS #
212391-63-4 (HCl) 185039-89-8 (free base) 1933496-20-8 (HCl hydrate)
Synonym
PD0166285; PD 0166285; PD0166285; PD166285; PD 166285; PD166285.
IUPAC/Chemical Name
6-(2,6-dichlorophenyl)-2-((4-(2-(diethylamino)ethoxy)phenyl)amino)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one
InChi Key
IFPPYSWJNWHOLQ-UHFFFAOYSA-N
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)
SMILES Code
O=C1C(C2=C(Cl)C=CC=C2Cl)=CC3=CN=C(NC4=CC=C(OCCN(CC)CC)C=C4)N=C3N1C
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
        
Biological target:
PD0166285 is a potent Wee1 and Chk1 inhibitor with activity at nanomolar concentrations (IC50=24 nM for Wee1 and 72 nM for Myt1).
In vitro activity:
B16 cells dramatically abrogated the G2 checkpoint and were found to arrest in the early G1 phase by treatment with 0.5 muM for 4 hours observed by flow cytometry. Cyclin D mRNA decreased within 4 hours observed by Real-time PCR. Rb was dephosphrylated for 24 hours. However, B16 cells did not undergo cell death after 0.5 muM treatment for 24 hours. Immnofluoscence microscopy showed that the cells become round and small in the morphogenesis. More interesting phenomena were that microtubule stabilization was blocked, and Wee1 distribution was restricted after treatment for 4 hours. Reference: BMC Cancer. 2006 Dec 19;6:292. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/17177986/
In vivo activity:
To determine the pharmacological characteristics and anti-tumor efficacy of PD0166285 on GBM outcome in vivo, GBM cells were first implanted subcutaneously (SC) into nude mice and determine the PD0166285 dosage sufficient to inhibit WEE1 activity in vivo. Mice were injected with various doses of PD0166285 (0, 20, 100, 200, or 400 µM in 100 µl) 20 days after tumor cells implantation. No adverse side effects were observed at the concentrations used. Tumors were removed 24 hr later and analyzed for inhibition of WEE1-mediated CDC2 phosphorylation by western blotting (Figure S4B). A single injection of 20 µM of the WEE1 inhibitor considerably reduced the CDC2 phosphorylation and was used in further experiments. Next, U251-FM human GBM cells were injected intracranially into nude mice. Mice with established GBMs were treated daily with PD0166285 or phosphate buffer solution (PBS) control via an intraperitoneal (IP) injection starting at day 14 after injection of the GBM cells. At day 15, the mice were sham irradiated or exposed to a single dose of 6 Gy. The results showed strong tumor progression in both irradiated and non-irradiated mock treated mice at 6 weeks after injection of the cells (Figures 6E and 6F). Similarly, the non-irradiated PD0166285 treated mice showed strong increase in tumor signal after 6 weeks. In contrary, irradiated mice treated with PD0166285 showed significant tumor regression 6 weeks after tumor injection (Figures 6E and 6F). Additionally, tumor burden was markedly reduced in this animal group (Figure 6G). Survival analysis showed a significant (p = 0.001) advantage for combining irradiation with PD0166285 (Figure 6H). These results indicate that pharmacological targeting of WEE1 sensitizes U251-FM GBM tumors to IR in vivo. Reference: Cancer Cell. 2010 Sep 14;18(3):244-57. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20832752/
Solvent mg/mL mM
Solubility
DMSO 60.0 117.10
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 512.43 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
1. Hashimoto O, Shinkawa M, Torimura T, Nakamura T, Selvendiran K, Sakamoto M, Koga H, Ueno T, Sata M. Cell cycle regulation by the Wee1 inhibitor PD0166285, pyrido [2,3-d] pyimidine, in the B16 mouse melanoma cell line. BMC Cancer. 2006 Dec 19;6:292. doi: 10.1186/1471-2407-6-292. PMID: 17177986; PMCID: PMC1770931. 2. Wang Y, Li J, Booher RN, Kraker A, Lawrence T, Leopold WR, Sun Y. Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator. Cancer Res. 2001 Nov 15;61(22):8211-7. PMID: 11719452.
In vivo protocol:
1. Mir SE, De Witt Hamer PC, Krawczyk PM, Balaj L, Claes A, Niers JM, Van Tilborg AA, Zwinderman AH, Geerts D, Kaspers GJ, Peter Vandertop W, Cloos J, Tannous BA, Wesseling P, Aten JA, Noske DP, Van Noorden CJ, Würdinger T. In silico analysis of kinase expression identifies WEE1 as a gatekeeper against mitotic catastrophe in glioblastoma. Cancer Cell. 2010 Sep 14;18(3):244-57. doi: 10.1016/j.ccr.2010.08.011. PMID: 20832752; PMCID: PMC3115571.
1: Chen ZL, Xie C, Zeng W, Huang RQ, Yang JE, Liu JY, Chen YJ, Zhuang SM. Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases. Signal Transduct Target Ther. 2024 Jul 12;9(1):181. doi: 10.1038/s41392-024-01896-z. PMID: 38992067; PMCID: PMC11239683. 2: Zhou Z, Zhong L, Chu X, Wan P, Dan W, Shao X, Chen S, Zhang Z, Lu Y, Liu B. HDAC11 mediates the ubiquitin-dependent degradation of p53 and inhibits the anti-leukemia effect of PD0166285. Med Oncol. 2023 Oct 7;40(11):325. doi: 10.1007/s12032-023-02196-2. PMID: 37805625. 3: Lockhead S, Moskaleva A, Kamenz J, Chen Y, Kang M, Reddy AR, Santos SDM, Ferrell JE Jr. The Apparent Requirement for Protein Synthesis during G2 Phase Is due to Checkpoint Activation. Cell Rep. 2020 Jul 14;32(2):107901. doi: 10.1016/j.celrep.2020.107901. PMID: 32668239; PMCID: PMC7802425. 4: de Gooijer MC, Buil LCM, Beijnen JH, van Tellingen O. ATP-binding cassette transporters limit the brain penetration of Wee1 inhibitors. Invest New Drugs. 2018 Jun;36(3):380-387. doi: 10.1007/s10637-017-0539-8. Epub 2017 Nov 17. PMID: 29147815. 5: Tsai TY, Theriot JA, Ferrell JE Jr. Changes in oscillatory dynamics in the cell cycle of early Xenopus laevis embryos. PLoS Biol. 2014 Feb 11;12(2):e1001788. doi: 10.1371/journal.pbio.1001788. PMID: 24523664; PMCID: PMC3921120. 6: Chang JB, Ferrell JE Jr. Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle. Nature. 2013 Aug 29;500(7464):603-7. doi: 10.1038/nature12321. Epub 2013 Jul 17. PMID: 23863935; PMCID: PMC3758429. 7: PosthumaDeBoer J, Würdinger T, Graat HC, van Beusechem VW, Helder MN, van Royen BJ, Kaspers GJ. WEE1 inhibition sensitizes osteosarcoma to radiotherapy. BMC Cancer. 2011 Apr 29;11:156. doi: 10.1186/1471-2407-11-156. PMID: 21529352; PMCID: PMC3103478. 8: Mir SE, De Witt Hamer PC, Krawczyk PM, Balaj L, Claes A, Niers JM, Van Tilborg AA, Zwinderman AH, Geerts D, Kaspers GJ, Peter Vandertop W, Cloos J, Tannous BA, Wesseling P, Aten JA, Noske DP, Van Noorden CJ, Würdinger T. In silico analysis of kinase expression identifies WEE1 as a gatekeeper against mitotic catastrophe in glioblastoma. Cancer Cell. 2010 Sep 14;18(3):244-57. doi: 10.1016/j.ccr.2010.08.011. PMID: 20832752; PMCID: PMC3115571. 9: Hashimoto O, Shinkawa M, Torimura T, Nakamura T, Selvendiran K, Sakamoto M, Koga H, Ueno T, Sata M. Cell cycle regulation by the Wee1 inhibitor PD0166285, pyrido [2,3-d] pyimidine, in the B16 mouse melanoma cell line. BMC Cancer. 2006 Dec 19;6:292. doi: 10.1186/1471-2407-6-292. PMID: 17177986; PMCID: PMC1770931. 10: Kawabe T. G2 checkpoint abrogators as anticancer drugs. Mol Cancer Ther. 2004 Apr;3(4):513-9. PMID: 15078995. 11: Hashimoto O, Ueno T, Kimura R, Ohtsubo M, Nakamura T, Koga H, Torimura T, Uchida S, Yamashita K, Sata M. Inhibition of proteasome-dependent degradation of Wee1 in G2-arrested Hep3B cells by TGF beta 1. Mol Carcinog. 2003 Apr;36(4):171-82. doi: 10.1002/mc.10111. PMID: 12669309. 12: Li J, Wang Y, Sun Y, Lawrence TS. Wild-type TP53 inhibits G(2)-phase checkpoint abrogation and radiosensitization induced by PD0166285, a WEE1 kinase inhibitor. Radiat Res. 2002 Mar;157(3):322-30. doi: 10.1667/0033-7587(2002)157[0322:wttigp]2.0.co;2. PMID: 11839095. 13: Wang Y, Li J, Booher RN, Kraker A, Lawrence T, Leopold WR, Sun Y. Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator. Cancer Res. 2001 Nov 15;61(22):8211-7. PMID: 11719452.

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