All AbMole products are for research use only, cannot be used for human consumption.
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.
J Nucl Med. 2018 Nov 21.
MEK inhibition induces therapeutic iodine uptake in a murine model of anaplastic thyroid cancer.
GDC-0941 (Pictilisib) purchased from AbMole
J Exp Clin Cancer Res. 2018 Sep 21;37(1):234.
The LAT1 inhibitor JPH203 reduces growth of thyroid carcinoma in a fully immunocompetent mouse model.
GDC-0941 (Pictilisib) purchased from AbMole
Mol Cancer Res. 2018 Aug 14.
Comprehensive Genomic Profiling of Patient-matched Head and Neck Cancer Cells: A Preclinical Pipeline for Metastatic and Recurrent Disease.
GDC-0941 (Pictilisib) purchased from AbMole
ChemMedChem. 2018 Dec 6.
Identifying Lysophosphatidic Acid Acyltransferase β (LPAAT-β) as the Target of a Nanomolar Angiogenesis Inhibitor from a Phenotypic Screen Using the Polypharmacology Browser PPB2.
GDC-0941 (Pictilisib) purchased from AbMole
Mol Cancer. 2017 May 22;16(1):93.
PIK3CA hotspot mutations differentially impact responses to MET targeting in MET-driven and non-driven preclinical cancer models
GDC-0941 (Pictilisib) purchased from AbMole
Oncotarget. 2017 Apr 11;8(15): 24604–24620.
Combined MEK and Pi3’-kinase inhibition reveals synergy in targeting thyroid cancer in vitro and in vivo
GDC-0941 (Pictilisib) purchased from AbMole
BioRxiv. 2017 July 18;1-45.
PIK3CAH1047R-induced paradoxical ERK activation results in resistance to BRAFV600E specific inhibitors in BRAFV600E PIK3CAH1047R double mutant thyroid tumors.
GDC-0941 (Pictilisib) purchased from AbMole
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Source | Journal of Nuclear Medicine (2018 Nov). Figure 3. GDC-0941 (AbMole Bioscience Inc.) |
| Method | oral gavage | |
| Cell Lines | single mutant BRAFV600E mice | |
| Concentrations | 50 mg/kg | |
| Incubation Time | 10 days | |
| Results | The selective BRAFV600E inhibitor PLX-4720 did not increase Nis mRNA transcription, nor did the PI3K inhibitor GDC-0941 alone or in combination with PD-325901 or PLX-4720. |
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Source | Journal of Experimental & Clinical Cancer Research (2018). Figure 4. GDC-0941 (Abmole Bioscience) |
| Method | oral gavage | |
| Cell Lines | BRAFV600E/PIK3CAH1047R double-mutant mouse | |
| Concentrations | 50 mg/kg | |
| Incubation Time | 10 days | |
| Results | While Pi3K inhibition did not induced any change in Slc7a5 transcript abundance, MEK inhibition induced more than 50% reduction. |
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Source | Molecular Cancer Research (2018). Figure 2. GDC-0941 (Abmole Bioscience) |
| Method | cell viability assay | |
| Cell Lines | M-SCC-14A, UM-SCC-14B, and UM-SCC-14C cells | |
| Concentrations | ||
| Incubation Time | 72 hours | |
| Results | Interestingly, pictilisib was less effective at impairing proliferation in UM-SCC-14B than in the other two matched cell lines. |
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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. |
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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. |
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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. |
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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. |
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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. |
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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). |
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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). |
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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). |
.figure 1..jpg) |
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). |
. gdc-0941, figure 5.jpg) |
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). |
. gdc-0941, figure 4.jpg) |
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). |
. gdc-0941, figure 1.jpg) |
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). |
| 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 |
| Molecular Weight | 513.64 |
| Formula | C23H27N7O3S2 |
| CAS Number | 957054-30-7 |
| Solubility (25°C) | DMSO 40 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related PI3K Products |
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| RV-1729
RV-1729 is an inhibitor of the phosphatidylinositol 3-kinase-δ (PI3Kδ). |
| Vulolisib
Vulolisib is a potent and orally active phosphatidylinositol 3-kinase (PI3K) inhibitor, with IC50 values of 0.2 nM, 168 nM, 90 nM and 49 nM for PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ, respectively. |
| Vps34-IN-4
Vps34-IN-4 is a potent, selective, and orally active inhibitor of VPS34. |
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