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GDC-0941

Cat. No. M1715
GDC-0941 Structure
Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
50mg USD 180 In stock
100mg USD 280 In stock
200mg USD 380 In stock
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Quality Control
Biological Activity

GDC-0941, a selective and potent PI3K inhibitor, is highly efficacious both in combination with trastuzumab and in the treatment of trastuzumab-resistant cells and tumors. GDC-0941 inhibited the growth of >70% of breast cancer cell lines tested, with EC50's <1 µM. GDC-0941 also demonstrated antitumor activity in preclinical models of breast cancer.

Product Citations
Customer Product Validations & Biological Datas
Source BioRxiv (2017). Figure 6. GDC-0941 (Abmole Bioscience, Hong-Kong, China)
Method western blot
Cell Lines 8505c cells
Concentrations 1 μM
Incubation Time
Results Paradoxical ERK hyperphosphorylation was not detectable when cells were subjected to GDC-0941 in addition to PLX-4032 drug dilutions. When we treated them with the same concentrations of PLX-4032, 8505c and SW1736 cells did not exhibit paradoxical ERK activation.
Source BioRxiv (2017). Figure 4. GDC-0941 (Abmole Bioscience, Hong-Kong, China)
Method paradoxical activation
Cell Lines Thyroglobulin Cre ERT2 mice
Concentrations 50 mg/kg
Incubation Time 10 d
Results Only GDC-0941 and drug combination treated animals showed tumor burden reduction. PLX-4720 treated animals displayed an elevation in tumor burden that was not statistically different from the controls but from the two other groups.
Source BioRxiv (2017). Figure 3. GDC-0941 (Abmole Bioscience, Hong-Kong, China)
Method paradoxical activation
Cell Lines Thyroglobulin Cre ERT2 mice
Concentrations 50 mg/kg
Incubation Time 70 d
Results When treated with drug combination, ERK paradoxical activation was abolished resulting in ERK phosphorylation level comparable to controls. AKT phosphorylation was not affected by PLX-4720 while GDC-0941 treatment resulted in a small but significant reduction of AKT phosphorylation.
Source BioRxiv (2017). Figure 2. GDC-0941 (Abmole Bioscience, Hong-Kong, China)
Method Histological presentation
Cell Lines Thyroglobulin Cre ERT2 mice
Concentrations 50 mg/kg
Incubation Time 70 d
Results GDC-0941-treated mice had smaller thyroid sections, while presenting a similar histology compared to controls (Fig. 2B) with a mixture of PTC containing small ATC foci.
Source BioRxiv (2017). Figure 1. GDC-0941 (Abmole Bioscience, Hong-Kong, China)
Method tumor burden assay
Cell Lines Thyroglobulin Cre ERT2 mice
Concentrations 50 mg/kg
Incubation Time 70 d
Results GDC-0941 treated animals presented an initial tumor burden reduction of 20% then tumor size stabilized for the rest of the treatment period. Interestingly, when a drug combination of PLX-4720 and GDC-0941 was administered, mice showed a robust response with 60% lower tumor burden after 6 weeks followed by stabilization until the end of the experiment.
Source Oncotarget (2017). GDC-0941, Figure 4. (AbMole Bioscience, Hong-Kong, China)
Method Western blot
Cell Lines ATC cell
Concentrations 50 mg/kg
Incubation Time 24 h
Results Interestingly, PD-325901 treated mice showed a clear improvement in histology with some almost normal follicles and smaller PTC areas. GDC-0941 did not induce a beneficial effect at the histological level. Finally, mice treated with the combination, although resulting in smaller sections, seemed to have a similar histological presentation to PD-325901 alone treated animals (Figure 4C).
Source Oncotarget (2017). GDC-0941, Figure 3. (AbMole Bioscience, Hong-Kong, China)
Method Western blot
Cell Lines ATC cell
Concentrations
Incubation Time 24 h
Results ERK1/2 and AKT phosphorylation were assessed first to demonstrate the drug efficiency. ERK1/2 phosphorylation ratio (p-ERK1/2 normalized to total ERK) was strongly decreased in all cell lines when treated with PD-325901 alone or in combination with GDC-0941. Similarly, GDC-0941 induced a strong reduction of AKT phosphorylation ratio (Figure 3).
Source Oncotarget (2017). GDC-0941, Figure 2. (AbMole Bioscience, Hong-Kong, China)
Method apoptosis assay
Cell Lines OCUT-2 cells
Concentrations 1 μM
Incubation Time 24 h
Results Only the OCUT-2 cell line already showed increased apoptosis (double positive annexinV and PI cells) when treated with the combination for 24 h (Figure 2A). However, after 48 h of combination treatment, all three cell lines (Figure 2B and Supplementary Figure 1) had elevated double positive annexinV/PI cells (late apoptosis) and annexinV positive cells (early apoptosis).
Source Oncotarget (2017). GDC-0941, Figure 1. (AbMole Bioscience, Hong-Kong, China)
Method
Cell Lines SW1736 and OCUT-2 cell lines
Concentrations 2 μM, 400 nM, 80 nM, 16 nM, 3.2 nM
Incubation Time 72 h
Results We investigated the effect of the drugs on cell cycling. PD-325901 alone or in combination with GDC-0941 induced a G1 cycle arrest in SW1736 and 8505c cell lines. However, in OCUT-2, a significant effect was only observed for the combination (Figure 1C).
Source Mol Cancer (2017). GDC-0941, Figure 5. (AbMole BioScience, Hongkong, China)
Method cell proliferation assay
Cell Lines NIH3T3 cells
Concentrations 0-100 nM
Incubation Time 16 h
Results Combination treatment led to more effective abrogation of AKT phosphorylation than either tepotinib or pictilisib alone, but p-S6 levels were generally unaltered (Fig. 5b).
Source Mol Cancer (2017). GDC-0941, Figure 4. (AbMole BioScience, Hongkong, China)
Method In vivo tumor growth delay experiments
Cell Lines
Concentrations 50 mg/kg
Incubation Time 5 d
Results Comparison of average tumor sizes of vector vs. H1047R at the experimental endpoint showed significant resistance to tepotinib in H1047R tumors (p = 0.012), as well as higher efficacy of pictilisib in the same group (p = 0.026; Fig. 4d).
Source Mol Cancer (2017). GDC-0941, Figure 1. (AbMole BioScience, Hongkong, China)
Method Cell viability/toxicity assays
Cell Lines NIH3T3 cells
Concentrations 0-100 nM
Incubation Time 16 h
Results PI3K inhibition by pictilisib was similarly effective in reducing p-AKT levels in these three cell lines, but at a concentration of 100 nM p-S6 levels were lower in cells harboring PIK3CA mutations (Fig. 1b).
Protocol
Cell Experiment
Cell lines U87MG cell line
Preparation method Proliferation Assay. The human tumor cell lines used wereobtained from the ATCC. Cells were plated at 4 × 104 cells/ mL and cultured at 37 °C with 5% CO2 in DMEM supplemented with 10% fetal calf serum, and L-glutamine. Test compound was added to replicate wells in a volume of 10 µL such that the final DMSO concentration did not exceed 0.2%. After 4 days of incubation, 10 µL of Alamar Blue reagent was added and developed for 6 h at 37 °C before measuring the fluorescence excitation/emission (wavelength 540/595 nm) using a Victor plate reader. The reported IC50 values are means of at least two independent experiments with variations of less than 20%.
Concentrations 0~10µM
Incubation time 4 days
Animal Experiment
Animal models Human tumor xenografts of U87MG glioblastoma of female NCr athymic mice
Formulation 10% DMSO, 5% Tween 20, 85% water
Dosages 75 mg/kg once daily
Administration oral gavage
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 513.64
Formula C23H27N7O3S2
CAS Number 957054-30-7
Purity 100.00%
Solubility DMSO
Storage at -20°C
References

Phosphatidylinositol 3-Kinase/Akt Signaling Pathway Activates the WNK-OSR1/SPAK-NCC Phosphorylation Cascade in Hyperinsulinemic db/db Mice.
Nishida et al. Hypertension. 2012 Oct;60(4):981-90. PMID: 22949526.

Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: Eliminating activity by targeting at different levels.
Bressanin et al. Oncotarget. 2012 Aug;3(8):811-23. PMID: 22885370.

Design, Synthesis and Anticancer Activity of 4-Morpholinothieno[3,2-d]pyrimidine Derivatives Bearing Arylmethylene Hydrazine Moiety.
Zhu et al. Chem Pharm Bull (Tokyo). 2012;60(8):1037-45. PMID: 22863708.

GDC-0941, a novel class I selective PI3K inhibitor, enhances the efficacy of docetaxel in human breast cancer models by increasing cell death in vitro and in vivo.
Wallin et al. Clin Cancer Res. 2012 Jul 15;18(14):3901-11. PMID: 22586300.

ErbB3 inhibitory surrobodies inhibit tumor cell proliferation in vitro and in vivo.
Foreman et al. Mol Cancer Ther. 2012 Jul;11(7):1411-20. PMID: 22553357.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: GDC-0941 supplier, PI3K, inhibitors

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