ci-1033 (canertinib)  (Pfizer Inc)

Journal: Cell reports

Article Title: Mitf is a Schwann cell sensor of axonal integrity that drives nerve repair.

doi: 10.1016/j.celrep.2023.113282

Figure Lengend Snippet: Figure 5. Abrogation of Nrg-ErbB-PI3K-PI5K-mTorc2 signaling promotes Mitf nuclear translocation (A) Diagram of activating (green) and inhibiting (red) phosphorylation sites (P) of the Mit/Tfe family. The kinases that regulate each of those phosphorylation sites and the pharmacological inhibitors used in primary culture to target each of these kinases are indicated. (B) Diagram of SC primary culture with inhibitors. (C–N0) Primary SC culture derived from dissociated sciatic nerves of P4 WT mice, stained for Mitf (green) and Hoechst (blue). (C–C0) Primary SCs were cultured with DMSO (control), (D-D0) trametinib (MEK), (E and E0) SCH772984 (ERK1/2), (F and F0) enzastaurin (PKC), (G and G0) BIO (GSK3), (H and H0) MK-2206 (AKT), (I and I0) Torin (mTorc1/2), (J and J0) YM201636 (Pikfyve), (K and K0) VPS34-IN1 (Vps34), (L and L0) canertinib (ErbB), (M and M0) hNrg1, and (N and N0) rapamycin (mTorc1). Scale bar, 30 mm. (O) Examples of Mitf subcellular localization (top) and quantification of Mitf enrichment in the cytoplasm (pink), uniformly distributed (purple) or enriched in the nucleus (blue). n = 3 independent experiments for each inhibitor, n > 100 cells per experiment. The data are represented as the mean + SEM. (P and Q) Models of Mitf cytoplasmic retention and translocation into the SC nucleus.

Article Snippet: REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies Chicken Polyclonal Anti-Glial Fibrillary Acidic Protein (GFAP) Aviva Systems Biology Cat# OAPC00115; RRID: N/A Donkey anti-Goat IgG (H + L) CrossAdsorbed Secondary Antibody; Alexa FluorTM 555 Thermo Fisher Scientific A-21432; RRID:AB_2535853 Donkey anti-Mouse IgG (H + L) Highly Cross-Adsorbed Secondary Antibody; Alexa FluorTM 555 Thermo Fisher Scientific Cat# A-31570; RRID:AB_2536180 Donkey anti-Rabbit IgG (H + L) Highly Cross-Adsorbed Secondary Antibody; Alexa FluorTM 647 Thermo Fisher Scientific Cat# A-31573; RRID:AB_2536183 Goat anti-Chicken IgY (H + L) Secondary Antibody; Alexa FluorTM 555 Thermo Fisher Scientific A-21437; RRID:AB_2535858 Goat Anti-Human Sox10 Polyclonal antibody R and D Systems Cat# AF2864; RRID:AB_442208 Goat anti-Mouse IgG (H + L) Highly CrossAdsorbed Secondary Antibody; Alexa FluorTM Plus 680 Thermo Fisher Scientific Cat# A32729; RRID:AB_2633278 Goat anti-Mouse IgG (H + L) Secondary Antibody; DyLightTM 800 4X PEG Thermo Fisher Scientific Cat# SA5-35521; RRID:AB_2556774 Goat anti-Rabbit IgG (H + L) Highly CrossAdsorbed Secondary Antibody; Alexa FluorTM 680 Thermo Fisher Scientific Cat# A-21109; RRID:AB_2535758 Goat anti-Rabbit IgG (H + L) Secondary Antibody; DyLightTM 800 4X PEG Thermo Fisher Scientific Cat# SA5-35571; RRID:AB_2556775 Goat Polyclonal Anti-GFAP Antibody Aviva Systems Biology Cat# OAEB01041; RRID:AB_10885969 Mouse Anti-Paxillin Monoclonal Antibody; Unconjugated; Clone 349 BD Biosciences Cat# 610051; RRID:AB_397463 Mouse Anti-Rabbit Glyceraldehyde-3phosphate dehydrogenase (GAPDH) Monoclonal Antibody; Clone 6C5 Fitzgerald Industries International Cat# 10R-G109a; RRID:AB_1285808 Rabbit Polyclonal Anti-MiTF antibody Abcam Cat# ab122982; RRID:AB_10902226 Rabbit Polyclonal anti-MITF C terminus (CGTMPESSPAYSIPRKMGSNLEDILMD) This paper # 7416; RRID: N/A Rabbit Polyclonal anti-MITF N terminus (DLVNRIIKQEPVLENCSQE) This paper # 7414; RRID: N/A Rabbit Polyclonal anti-S100 Abcam Cat# ab868; RRID:AB_306716 Biological samples Mouse: Germplasm; Mtmr2tm1a(KOMP)Mbp KOMP/IKMC Project # 30275 Chemicals, peptides, and recombinant proteins Alexa FluorTM 488 Phalloidin Thermo Fisher Scientific Cat# A12379 BIO Sigma-Aldrich Cat# B1686; CAS 667463-62-9 Canertinib (CI-1033) Selleck Chemicals LLC Cat# S1019; CAS 267243-28-7 Enzastaurin (LY317615) Selleck Chemicals LLC Cat# S1055; CAS 170364-57-5 (Continued on next page) Cell Reports 42, 113282, November 28, 2023 19

Techniques: Translocation Assay, Phospho-proteomics, Derivative Assay, Staining, Cell Culture, Control

Journal: International Journal of Genomics

Article Title: The Effect of Canertinib on Sensitivity of Cytotoxic Drugs in Tamoxifen-Resistant Breast Cancer Cells In Vitro

doi: 10.1155/2018/7628734

Figure Lengend Snippet: Chemical structure of canertinib (EGFR-irreversible tyrosine kinase inhibitor).

Article Snippet: Clinical grade canertinib (CI-1033) and cytotoxic drugs (paclitaxel, etoposide, vinorelbine, and daunorubicin) were purchased from Sigma Chemical Co. (Sigma-Aldrich, Egypt).

Techniques:

Journal: International Journal of Genomics

Article Title: The Effect of Canertinib on Sensitivity of Cytotoxic Drugs in Tamoxifen-Resistant Breast Cancer Cells In Vitro

doi: 10.1155/2018/7628734

Figure Lengend Snippet: Measuring of EGFR and c-erbB2 expression; activation of ERK1/2 and AKT in MCF-7, T47D, and their tamoxifen-resistant derivative cells MCF-7(TamR) and T47D (TamR) cells, respectively. (a) Changes in levels of total EGFR and c-erbB2 expression by Western blot. (b) Changes in levels of p-EGFR and p-c-erbB2 expression by Western blot. (c) Changes in levels of expression and activation of ERK1/2 and AKT by Western blot. (d) Changes in levels of EGFR expression and activation in t47d cells before and after the development of tamoxifen resistance by Western blot. (e) The inhibitory effects of canertinib on the activation of EGFR, Akt, and ERK1/2 and their encoded protein in both MCF-7 and MCF-7(TamR) cells by Western blot.

Article Snippet: Clinical grade canertinib (CI-1033) and cytotoxic drugs (paclitaxel, etoposide, vinorelbine, and daunorubicin) were purchased from Sigma Chemical Co. (Sigma-Aldrich, Egypt).

Techniques: Expressing, Activation Assay, Western Blot

Journal: International Journal of Genomics

Article Title: The Effect of Canertinib on Sensitivity of Cytotoxic Drugs in Tamoxifen-Resistant Breast Cancer Cells In Vitro

doi: 10.1155/2018/7628734

Figure Lengend Snippet: Effect on growth of MCF-7 (red) and MCF-7(TamR) (blue) cells of a 9-day treatment of the EGFR inhibitors (a) canertinib and (b) canertinib added to the cell culture medium and refreshed on day 5 (test comparing growth inhibition between cell lines at a given concentration of EGFR inhibitor). ∗ indicates p < 0.05, ∗∗ indicates p < 0.01, ∗∗∗ indicates p < 0.001. Error bars indicate standard deviation.

Article Snippet: Clinical grade canertinib (CI-1033) and cytotoxic drugs (paclitaxel, etoposide, vinorelbine, and daunorubicin) were purchased from Sigma Chemical Co. (Sigma-Aldrich, Egypt).

Techniques: Cell Culture, Inhibition, Concentration Assay, Standard Deviation

Journal: International Journal of Genomics

Article Title: The Effect of Canertinib on Sensitivity of Cytotoxic Drugs in Tamoxifen-Resistant Breast Cancer Cells In Vitro

doi: 10.1155/2018/7628734

Figure Lengend Snippet: Effect of EGFR inhibition with canertinib treatment on the sensitivity of MCF-7 and MCF-7(TamR) cells to a 48-hour treatment with (a) paclitaxel and (b) daunorubicin. Cells were subjected to a 48-hour cytotoxic treatment with the addition of (red) 0 μ M, (blue) 0.1 μ M, or (green) 1 μ M canertinib before 4 days recovery in the same medium minus the cytotoxic. P values calculated from a paired t -test comparing growth inhibition between cells untreated with canertinib, both of which were treated with a given concentration of daunorubicin or paclitaxel. ∗ indicates p < 0.05 of 0 μ M canertinib. Error bars indicate standard deviation.

Article Snippet: Clinical grade canertinib (CI-1033) and cytotoxic drugs (paclitaxel, etoposide, vinorelbine, and daunorubicin) were purchased from Sigma Chemical Co. (Sigma-Aldrich, Egypt).

Techniques: Inhibition, Concentration Assay, Standard Deviation

Journal: International Journal of Genomics

Article Title: The Effect of Canertinib on Sensitivity of Cytotoxic Drugs in Tamoxifen-Resistant Breast Cancer Cells In Vitro

doi: 10.1155/2018/7628734

Figure Lengend Snippet: Effect of EGFR inhibition with canertinib treatment on the sensitivity of (a) MCF-7 and (b) MCF-7(TamR) cells to carboplatin. Cells were subjected to a 9-day treatment with carboplatin with the addition of (red) 0 μ M, (blue) 0.1 μ M, or (green) 1 μ M canertinib to the culture medium for the full length of the treatment, refreshed on day 5. P values calculated from a paired t -test comparing growth inhibition between cells treated with canertinib in addition to a given concentration of paclitaxel. ∗ indicates p < 0.05, ∗∗ indicates p < 0.01, ∗∗∗ indicates p < 0.001 of 0 μ M canertinib. Error bars indicate standard deviation.

Article Snippet: Clinical grade canertinib (CI-1033) and cytotoxic drugs (paclitaxel, etoposide, vinorelbine, and daunorubicin) were purchased from Sigma Chemical Co. (Sigma-Aldrich, Egypt).

Techniques: Inhibition, Concentration Assay, Standard Deviation

Journal: Biomedicines

Article Title: A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood–Brain Barrier

doi: 10.3390/biomedicines10081988

Figure Lengend Snippet: b.End5 cells viability upon exposure to drugs. B.End5 cells were treated with the indicated concentrations of each drug, or DMEM (untreated), for 24 h. Cell viability was assessed by the MTT assay, and the values are presented as percentage relative to untreated cells. Mol1, Mol2, Mol4, Mol6, CI-1033, KW-2478, BKM120, FTY720, FTY720-P, MB, and MH caused no toxicity at the lowest concentrations tested. All values are mean ± SEM of three independent experiments performed in triplicate. Statistical significances are shown as * p < 0.5, ** p < 0.01, and *** p < 0.001 vs. untreated.

Article Snippet: PI3K inhibitors (Molecules 1–6), CI-1033, and KW-2478 were acquired from MolPort (MolPort SIA, Riga, Latvia) and BKM120 was kindly provided by MedChemExpress (MedChemExpress, Monmouth Junction, NJ, USA).

Techniques: MTT Assay