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PF-477736

Cat. No. M1764
PF-477736 Structure
Synonym:

PF-0044736

Size Price Availability Quantity
10mg USD 160 In stock
50mg USD 520 In stock
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Quality Control
Biological Activity

PF-477736 is a selective checkpoint kinase 1 (Chk1) inhibitor with Ki values of 0.49 nM and 47 nM for CHK1 and CHK2 respectively.A proprietary compound PF-477736 targets cell cycle checkpoint kinase 1 (chk1) with potential chemopotentiation activity.Chk1 inhibitor PF-477736 inhibits chk1, an ATP-dependent serine-threonine kinase that is a key component in the DNA replication-monitoring S/G2 checkpoint system.

Protocol
Cell Experiment
Cell lines p53-defective human cancer cell lines HT29 cells
Preparation method IC50 MTT.
The proliferation assays were done using an MTT assay. The IC50 assay measures the antiproliferative effects of PF-00477736 on p53-defective human cancer cell lines. Cells in each line were seeded in complete medium at an exponentially growing density in 96-well assay plate and allowed to attach for 16 h. Serial dilutions of PF-00477736 were then done, and appropriate controls were added to each plate. Cells were incubated with drug for 96 h. After incubation, MTT working stock diluted in complete medium was added to each well, and cells were incubated for 4 h. After centrifugation and supernatant removal, DMSO was added to each well and plates were read on SpectraMax plate reader at 540 nm. IC50 and PF50 results were calculated by concentration-response curve fitting using a Microsoft Excel–based four-variable analysis method.
Concentrations 0, 180, 360 and 540 n M
Incubation time 96 h
Animal Experiment
Animal models Colo205 cells tumour Xenograft Models in Athymic Nude Mice
Formulation 50 nM sodium acetate buffer and 4% dextrose (pH 4)
Dosages 4-60 mg/kg q3d × 4
Administration i.p.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 419.48
Formula C22H25N7O2
CAS Number 952021-60-2
Purity 100.00%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
Source Sci Rep (2017). Figure 6. PF-477736 (Abmole Bioscience)
Method i.p.
Cell Lines Xenograft mouse model
Concentrations 20 mg/kg
Incubation Time 1–5 day
Results While vehicle-treated xenograft tumors derived from H-82 (Fig. 6D), H-526 (Fig. 6E) and H-69 (Fig. 6F) cells displayed a rapid growth, both VE-822 and PF-477736 treatment led to a massively delayed tumor growth in all three models, which was mimicked by a substantial reduction in Ki67 staining on histological examination in tumors that were excised following completion of treatment (Fig. 6G,H).
Rating
Source Sci Rep (2017). Figure 5. PF-477736 (Abmole Bioscience)
Method i.p.
Cell Lines Xenograft mouse model
Concentrations 20 mg/kg
Incubation Time 1–5 day
Results While tumors displayed continuous growth in vehicle-treated animals, all tumors in the PF-477736-exposed cohort displayed a substantial volume reduction after completion of the second cycle
Rating
Source Sci Rep (2017). Figure 4. PF-477736 (Abmole Bioscience)
Method i.p.
Cell Lines Xenograft mouse model
Concentrations 20 mg/kg
Incubation Time 1–5 day
Results Contrary to these substantial therapeutic effects inflicted by VE-822 and PF-477736 in SCLC-bearing animals, we only observed a minute survival extension in VE-822- and PF-477736-treated NSCLC-bearing mice.
Rating
Source Sci Rep (2017). Figure 3. PF-477736 (Abmole Bioscience)
Method Immunofluorescence
Cell Lines SCLC and NSCLC cells
Concentrations 1.0 μM
Incubation Time 48 h
Results Fully in line with our immunofluorescence data, SCLC cell lines displayed a significantly stronger γH2AX signal following VE-822 and PF-477736 treatment, than their NSCLC counterparts
Rating
Source Sci Rep (2017). Figure 2. PF-477736 (Abmole Bioscience)
Method Flow cytometry
Cell Lines SCLC and NSCLC cell
Concentrations 0.1 μM, 1.0 μM, 3.0 μM
Incubation Time 48 h
Results Of note, the slow growing cell line RP2 was less sensitive to VE-822 and PF-477736, compared to cell lines RP1, 3 and 4. The rapidly proliferating SCLC cell line RP5 displayed the most pronounced sensitivity to the cell cycle checkpoint abrogating agents VE-822 and PF-477736.
Rating
Product Citations
References

PF-00477736 mediates checkpoint kinase 1 signaling pathway and potentiates docetaxel-induced efficacy in xenografts.
Zhang C, et al. Clin Cancer Res. 2009 Jul 15;15(14):4630-40. PMID: 19584159.

Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1.
Blasina A et al. Mol Cancer Ther. 2008 Aug;7(8):2394-404. PMID: 18723486.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: PF-477736, PF-0044736 supplier, CDK, inhibitors

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