Journal: British Journal of Cancer

Article Title: Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models

doi: 10.1038/s41416-025-03035-z

Figure Lengend Snippet: a Overview of PI3K/AKT/mTOR pathway. b Data sourced from MSK-IMPACT clinical sequencing cohort, n = 10,945 samples via cBioPortal (MSK, Nature Medicine 2017). Amp amplification, Mut mutation, Del homozygous deletion. The 20 tumour types with the highest cumulative mutation frequency are shown. Note that multiple mutations can occur within the same tumour sample, hence cumulative total can exceed 100%. c Western blots of PI3K/AKT/mTOR pathway output (phosS6-S235/236 and phos4EBP1-T37/46) in endometrial and breast cancer cell lines treated with the indicated inhibitors for 3–4 h followed by stimulation with 10 ng/ml insulin for 10 min. Drug concentrations were selected to represent clinical Cmaximum and Caverage for each drug and the mid-point of these. d Dose-response curves for indicated drugs at 72 h post-treatment. e IC50 values of sapanisertib compared with serabelisib + sapanisertib in breast and endometrial cancer cell lines; unpaired t-test. Error bars denote SD.

Article Snippet: The following compounds, >95% purity, were used in this study (supplier information in parentheses): serabelisib (Carbogen), sapanisertib (Cayman Chemical, 11811), paclitaxel (Apex Bio, A4393), carboplatin (Sigma, BP711), alpelisib (Cayman Chemical, 16986), capivasertib (Biorbyt, ORB1307109), everolimus (Cayman Chemical, 11597), inavolisib (Cayman Chemical, 37576), RLY-2608 (Medchem Express, HY-153306), STX-478 (Medchem Express, HY-156681) fulvestrant (Cayman Chemical, 10011269), elacestrant hydrochloride (Cayman Chemical 37298).

Techniques: Sequencing, Amplification, Mutagenesis, Western Blot

Journal: British Journal of Cancer

Article Title: Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models

doi: 10.1038/s41416-025-03035-z

Figure Lengend Snippet: Western blots of PI3K/AKT/mTOR pathway activity (phosAKT-S473, phosS6-S235/236 and phos4E-BP1-T37/46) in endometrial ( a ) and breast ( b ) cancer cell lines, stimulated with 10 ng/ml insulin followed by treatment with the indicated inhibitors for 3–4 h. c Dose-response curves for serabelisib + sapanisertib against indicated mutant-specific PI3Kα inhibitors at 72 h post-treatment. d Correlation plot of PI3K/AKT/mTOR pathway inhibitors comparing the potency (IC50) of indicated drugs with the in vitro levels of phos-4E-BP1-T37/46 and phos-S6-S235/236 after 3–4 hours treatment with indicated drugs at the average free-drug plasma concentration (Caverage) achieved in humans/in vivo models; data are means for breast and endometrial cancer cell lines used in this study. A diagram depicting action of 4E-BP1 and phoph4E-BP1 on eIF4E is also shown in panel ( d ). Error bars denoted SD.

Article Snippet: The following compounds, >95% purity, were used in this study (supplier information in parentheses): serabelisib (Carbogen), sapanisertib (Cayman Chemical, 11811), paclitaxel (Apex Bio, A4393), carboplatin (Sigma, BP711), alpelisib (Cayman Chemical, 16986), capivasertib (Biorbyt, ORB1307109), everolimus (Cayman Chemical, 11597), inavolisib (Cayman Chemical, 37576), RLY-2608 (Medchem Express, HY-153306), STX-478 (Medchem Express, HY-156681) fulvestrant (Cayman Chemical, 10011269), elacestrant hydrochloride (Cayman Chemical 37298).

Techniques: Western Blot, Activity Assay, Mutagenesis, In Vitro, Clinical Proteomics, Concentration Assay, In Vivo

Journal: British Journal of Cancer

Article Title: Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models

doi: 10.1038/s41416-025-03035-z

Figure Lengend Snippet: a Dose-response curves for carboplatin with different concentrations of serabelisib plus sapanisertib at 72 h post-treatment in endometrial cancer cell lines. b Dose-response curves for paclitaxel with different concentrations of serabelisib plus sapanisertib at 72 h post-treatment in endometrial cancer cell lines. c Dose-response curves for selinexor with different concentrations of serabelisib plus sapanisertib at 72 h post-treatment in endometrial cancer cell lines. d Dose-response curves for palbociclib with different concentrations of serabelisib plus sapanisertib at 72 h post-treatment in endometrial cancer cell lines. Error bars denote SD.

Article Snippet: The following compounds, >95% purity, were used in this study (supplier information in parentheses): serabelisib (Carbogen), sapanisertib (Cayman Chemical, 11811), paclitaxel (Apex Bio, A4393), carboplatin (Sigma, BP711), alpelisib (Cayman Chemical, 16986), capivasertib (Biorbyt, ORB1307109), everolimus (Cayman Chemical, 11597), inavolisib (Cayman Chemical, 37576), RLY-2608 (Medchem Express, HY-153306), STX-478 (Medchem Express, HY-156681) fulvestrant (Cayman Chemical, 10011269), elacestrant hydrochloride (Cayman Chemical 37298).

Techniques:

Journal: British Journal of Cancer

Article Title: Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models

doi: 10.1038/s41416-025-03035-z

Figure Lengend Snippet: a Generation of paclitaxel resistant cell lines, with dose-response curves of paclitaxel in parental and paclitaxel resistant cell lines at 72 h post-treatment. b Dose-response curves of sapanisertib plus serabelisib in parental and paclitaxel resistant cell lines at 72 h post-treatment. c Western blots of PI3K/AKT/mTOR pathway activity (phosAKT-S473, phosS6-S235/236 and phos4EBP1-T37/46) in AN3CA parental or paclitaxel resistant cell lines, stimulated with 10 ng/ml insulin followed by treatment with the indicated inhibitors for 3–4 h. d Quantification of the indicated phospho-AKT/S6/4EBP1 levels in vehicle-treated AN3CA parental or paclitaxel resistant samples. Error bars denote SD.

Article Snippet: The following compounds, >95% purity, were used in this study (supplier information in parentheses): serabelisib (Carbogen), sapanisertib (Cayman Chemical, 11811), paclitaxel (Apex Bio, A4393), carboplatin (Sigma, BP711), alpelisib (Cayman Chemical, 16986), capivasertib (Biorbyt, ORB1307109), everolimus (Cayman Chemical, 11597), inavolisib (Cayman Chemical, 37576), RLY-2608 (Medchem Express, HY-153306), STX-478 (Medchem Express, HY-156681) fulvestrant (Cayman Chemical, 10011269), elacestrant hydrochloride (Cayman Chemical 37298).

Techniques: Western Blot, Activity Assay

Journal: British Journal of Cancer

Article Title: Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models

doi: 10.1038/s41416-025-03035-z

Figure Lengend Snippet: a Efficacy of sapanisertib (0.5 mg/kg), serabelisib (75 mg/kg), paclitaxel (15 mg/kg) and their combinations in MDA-MB-361 xenografts. Drugs were initiated when tumour volume reached 300 mm 3 ; n = 7–8 mice per group. b Efficacy of sapanisertib (0.5 mg/kg), serabelisib (75 mg/kg), paclitaxel (15 mg/kg) and their combinations in AN3CA xenografts. Drugs were initiated when tumour volume reached 300 mm 3 ; n = 8 mice per group. c Efficacy of sapanisertib (0.5 mg/kg), serabelisib (75 mg/kg), paclitaxel (3.5 mg/kg) and their combinations, with and without an insulin-suppressing diet (ISD) in MDA-MB-361 xenografts. Drugs were initiated when tumour volume reached 250 mm 3 , n = 5–8 mice per group. d Efficacy of sapanisertib (0.5 mg/kg), serabelisib (75 mg/kg), paclitaxel (10 mg/kg) and their combinations, with and without ISD in AN3CA xenografts. Drugs were initiated when tumour volume reached 250 mm 3 , n = 6–8 mice per group. e AN3CA and MDA-MB-361 tumours were randomly harvested from chow and ISD groups treated with sapanisertib, sapanisertib and paclitaxel at study endpoint; n = 6 per group. Unpaired t-test with Welch’s correction. f Representative Western blots of PI3K-AKT-mTOR pathway activity (phosAKT-S473, phosS6-S235/236 and phos4EBP1-T37/46) in AN3CA and MDA-MB-361 tumours from indicated groups, 1 h post drug dosing; n = 3 tumours per group were randomly harvested and processed for Western blot. Error bars denote SEM.

Article Snippet: The following compounds, >95% purity, were used in this study (supplier information in parentheses): serabelisib (Carbogen), sapanisertib (Cayman Chemical, 11811), paclitaxel (Apex Bio, A4393), carboplatin (Sigma, BP711), alpelisib (Cayman Chemical, 16986), capivasertib (Biorbyt, ORB1307109), everolimus (Cayman Chemical, 11597), inavolisib (Cayman Chemical, 37576), RLY-2608 (Medchem Express, HY-153306), STX-478 (Medchem Express, HY-156681) fulvestrant (Cayman Chemical, 10011269), elacestrant hydrochloride (Cayman Chemical 37298).

Techniques: Western Blot, Activity Assay

Journal: Cells

Article Title: Bioengineering the Human Intestinal Mucosa and the Importance of Stromal Support for Pharmacological Evaluation In Vitro

doi: 10.3390/cells13221859

Figure Lengend Snippet: Ussing chamber apparatus used to assess the permeability of intestinal constructs in vitro. ( A ) A representative image of a 96-well Alvetex ® Scaffold insert used to produce full-thickness (FT) intestinal constructs for physiological permeability screening ( left ), and the insertion of the insert into the chamber ( right ). ( B ) A schematic representation of the direction of transport as measured using the Ussing chamber, with transport either measured apical–basal (A-B) or basal–apical (B-A) depending on the orientation of the tissue construct. ( C ) A schematic representation of the Ussing system with a ( D ) supporting photograph. The system consists of two reservoirs, with which analytes and carbogen gas are circulated within a water jacket that maintains the system at a constant temperature of 37 °C. Bioengineered constructs (full-thickness or epithelial-only) reside at the interface between the reservoirs, the orientation of which dictates the direction of transport. Analytes are added or sampled from each reservoir, respectively.

Article Snippet: Carbogen gas (95% O 2 , 5% CO 2 , BOC, Guilford, UK) was bubbled through the chamber system to oxygenate the assay medium and provide circulation to the system.

Techniques: Permeability, Construct, In Vitro