shp2 inhibitor shp099  (Novartis)

Journal: NPJ Precision Oncology

Article Title: WWP1 inhibition increases SHP2 inhibitor efficacy in colorectal cancer

doi: 10.1038/s41698-024-00650-6

Figure Lengend Snippet: a Knockdown of WWP1 decreases pAKT levels. b Feedback reactivation of AKT pathway following SHP2 inhibition. c Subcellular localization of PTEN and WWP1 after SHP099 treatment. d Protein interaction between WWP1 and PTEN. e WWP1 induces PTEN ubiquitination modification. f Increased PTEN ubiquitination levels with SHP099 treatment. g Increased PTEN membrane localization with I3C treatment. h I3C treatment reduces pAKT levels. i Combination of I3C and SHP099 remarkably suppresses the pAKT levels. Different CRC cell lines were respectively treated with I3C (200 μM) or SHP099 (20 μM). AKT/ERK bands are obtained after re-incubation of AKT/ERK antibody after pAKT/pERK exposure in a/b/c/h/i .

Article Snippet: SHP2 inhibitor (SHP099, #HY-100388) and WWP1 inhibitor (I3C, #HY-N0170) were purchased from MedChemExpress.

Techniques: Knockdown, Inhibition, Modification, Membrane, Incubation

Journal: NPJ Precision Oncology

Article Title: WWP1 inhibition increases SHP2 inhibitor efficacy in colorectal cancer

doi: 10.1038/s41698-024-00650-6

Figure Lengend Snippet: a Effects of WWP1 knockdown and SHP099 on CRC cell proliferation in vitro. b Effects of WWP1 knockdown and SHP099 on clone formation in CRC cells. c Effects of WWP1 overexpression and SHP099 on CRC cell proliferation in vitro. d Effects of WWP1 overexpression and SHP099 on clone formation in CRC cells. Different CRC cell lines were treated with SHP099 (20 μM). Each plot shows the mean ± SD of triplicate assays. * P < 0.05, ** P < 0.01, *** P < 0.005 and **** P < 0.001, by 2-tailed t test or one-way ANOVA.

Article Snippet: SHP2 inhibitor (SHP099, #HY-100388) and WWP1 inhibitor (I3C, #HY-N0170) were purchased from MedChemExpress.

Techniques: Knockdown, In Vitro, Over Expression

Journal: NPJ Precision Oncology

Article Title: WWP1 inhibition increases SHP2 inhibitor efficacy in colorectal cancer

doi: 10.1038/s41698-024-00650-6

Figure Lengend Snippet: a Inhibition of CRC cell proliferation by I3C and SHP099. b HSA synergy scores of I3C and SHP099 for inhibition of CRC cell proliferation. c Inhibition of CRC cell clone formation by I3C and SHP099. d Effects of I3C and SHP099 on apoptosis. e Effects of I3C and SHP099 on cell cycle. Different CRC cell lines were respectively treated with I3C (200 μM) or SHP099 (20 μM). Each plot shows the mean ± SD of triplicate assays. * P < 0.05, ** P < 0.01, *** P < 0.005 and **** P < 0.001, by 2-tailed t test or one-way ANOVA.

Article Snippet: SHP2 inhibitor (SHP099, #HY-100388) and WWP1 inhibitor (I3C, #HY-N0170) were purchased from MedChemExpress.

Techniques: Inhibition

Journal: NPJ Precision Oncology

Article Title: WWP1 inhibition increases SHP2 inhibitor efficacy in colorectal cancer

doi: 10.1038/s41698-024-00650-6

Figure Lengend Snippet: a I3C improves the efficacy of SHP2 inhibitor for tumor growth inhibition in vivo. b Combination of I3C and SHP099 reduces Ki-67 positive expression in xenograft tumors. c Combination of I3C and SHP099 increases Tunel assay positive expression in xenograft tumors. Mice were treated orally with I3C (100 mg/kg) or SHP099 (30 mg/kg) once daily from about 10 days after implantation. Each plot shows the mean ± SD of triplicate assays. * P < 0.05, ** P < 0.01, *** P < 0.005 and **** P < 0.001, by 2-tailed t test or one-way ANOVA.

Article Snippet: SHP2 inhibitor (SHP099, #HY-100388) and WWP1 inhibitor (I3C, #HY-N0170) were purchased from MedChemExpress.

Techniques: Inhibition, In Vivo, Expressing, TUNEL Assay

Journal: NPJ Precision Oncology

Article Title: WWP1 inhibition increases SHP2 inhibitor efficacy in colorectal cancer

doi: 10.1038/s41698-024-00650-6

Figure Lengend Snippet: a In normal intestinal mucosal epithelial cell, the MAPK and PI3K-AKT pathway are inactivated. b In untreated CRC cell, SHP2 mediates signaling of the MAPK and the PI3K-AKT pathway, and cell proliferation is active. c In SHP2-inhibited CRC cell, the WWP1/PTEN axis mediated feedback activation of AKT signaling, and cell proliferation is moderately inhibited. d In SHP2 and WWP1 co-inhibited CRC cell, AKT signaling is deeply blocked and cell proliferation is strongly inhibited.

Article Snippet: SHP2 inhibitor (SHP099, #HY-100388) and WWP1 inhibitor (I3C, #HY-N0170) were purchased from MedChemExpress.

Techniques: Activation Assay