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entrectinib  (MedChemExpress)


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    Structured Review

    MedChemExpress entrectinib
    MET overexpression causes resistance to osimertinib, sotorasib, poziotinib, and <t>entrectinib</t> (A) The indicated tetON-MET cells were induced with doxycycline for 48 h before lysis. Western blot analysis was performed with the indicated antibodies. (B) Cells were cultured with doxycycline for 24 h before being treated with the respective targeted therapies. Cellular viability was measured six days from treatment onset. Data are represented as mean of n = 3 ± SD.
    Entrectinib, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 95/100, based on 39 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/product/entrectinib/Entrectinib/pmc10391663-19-0-2
    Average 95 stars, based on 39 article reviews
    entrectinib - by Bioz Stars, 2026-10
    95/100 stars

    Images

    1) Product Images from "Overcoming MET-mediated resistance in oncogene-driven NSCLC"

    Article Title: Overcoming MET-mediated resistance in oncogene-driven NSCLC

    Journal: iScience

    doi: 10.1016/j.isci.2023.107006

    MET overexpression causes resistance to osimertinib, sotorasib, poziotinib, and entrectinib (A) The indicated tetON-MET cells were induced with doxycycline for 48 h before lysis. Western blot analysis was performed with the indicated antibodies. (B) Cells were cultured with doxycycline for 24 h before being treated with the respective targeted therapies. Cellular viability was measured six days from treatment onset. Data are represented as mean of n = 3 ± SD.
    Figure Legend Snippet: MET overexpression causes resistance to osimertinib, sotorasib, poziotinib, and entrectinib (A) The indicated tetON-MET cells were induced with doxycycline for 48 h before lysis. Western blot analysis was performed with the indicated antibodies. (B) Cells were cultured with doxycycline for 24 h before being treated with the respective targeted therapies. Cellular viability was measured six days from treatment onset. Data are represented as mean of n = 3 ± SD.

    Techniques Used: Over Expression, Lysis, Western Blot, Cell Culture


    Figure Legend Snippet:

    Techniques Used: Recombinant, Synthesized, Hybridization, Software

    Related Articles

    Liposomes:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

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    Injection:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

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    Fat:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Control:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Recombinant:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Biomarker Discovery:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Kinase Assay:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Staining:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Viability Assay:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Two Tailed Test:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Standard Deviation:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Expressing:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    RNAscope:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Derivative Assay:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Inhibition:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Activation Assay:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Data-independent acquisition:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Protein-Protein interactions:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Concentration Assay:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Comparison:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).

    Titration:

    Article Title: Fibroblasts neurotrophin signaling sustains pathological vascular maturation in rheumatoid arthritis
    Article Snippet: For neurotrophin (NT) stimulation, recombinant NGF (256-GF, R&D Systems), BDNF (11166-BD, R&D Systems), and NT3 (267-N3-005, R&D Systems) were reconstituted in DMSO or PBS and diluted in media.

    Article Title: Ceritinib overcomes proteasome inhibitor resistance in multiple myeloma by suppressing the protein folding response.
    Article Snippet: Proteasome inhibitors: bortezomib (PS-341; HY-10227) and carfilzomib (PR-171; HY-10455), ALK-inhibitors: crizotinib (PF-02341066; HY-50878), ceritinib (LDK378; HY-15656), brigatinib (AP-26113; HY-12857), entrectinib (NMS-E628; HY-12678), alectinib (CH5424802; HY13011), lorlatinib (PF-06463922; HY-12215) and ensartinib (X-396; HY-103714) ; FOXO-1 inhibitor (AS-1842856; HY-100596), IGF-1R/INSR inhibitor (NVP-AEW541; HY-50866), IGF1R/INSR inhibitor (BMS-536924; HY-10262), were purchased from MedChem Express (Monmouth Junction, NJ, USA).



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    Design and structures of <t>entrectinib-derived</t> PROTACs. (A) The co-crystal structure of entrectinib with TRKA kinase domain (PDB ID: 5KVT), in which the N -methyl piperazine is solvent accessible, as indicated by the red arrow. (B) The proposed modification on the piperazine ring for the linker introduction. (C and D) Chemical structures of the indicated compounds.
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    Design and structures of entrectinib-derived PROTACs. (A) The co-crystal structure of entrectinib with TRKA kinase domain (PDB ID: 5KVT), in which the N -methyl piperazine is solvent accessible, as indicated by the red arrow. (B) The proposed modification on the piperazine ring for the linker introduction. (C and D) Chemical structures of the indicated compounds.

    Journal: RSC Chemical Biology

    Article Title: Development of PROTACs for targeted degradation of oncogenic TRK fusions

    doi: 10.1039/d6cb00008h

    Figure Lengend Snippet: Design and structures of entrectinib-derived PROTACs. (A) The co-crystal structure of entrectinib with TRKA kinase domain (PDB ID: 5KVT), in which the N -methyl piperazine is solvent accessible, as indicated by the red arrow. (B) The proposed modification on the piperazine ring for the linker introduction. (C and D) Chemical structures of the indicated compounds.

    Article Snippet: Entrectinib (Selleck Chemicals, #S7998), GNF-8625 (MedChemExpress, #HY-131706A), CG-428 (Tocris, #7425), carfilzomib (MedChemExpress, #HY-10455), MLN4924 (Calbiochem, #5054770001), lenalidomide (Millipore Sigma, #901558), bafilomycin A1 (Cambridge Bioscience, #b0025) and pomalidomide (MedChemExpress, #HY-10984) were purchased from the indicated sources.

    Techniques: Derivative Assay, Solvent, Modification

    JWJ-01-378 induces potent degradation of TPM3-TRKA. (A) Immunoblot analysis of KM12 cells treated with DMSO, CG-428, JWJ-01-375, JWJ-01-377, JWJ-01-378, and entrectinib at the indicated doses for 2 hours. (B) Immunoblot analysis of KM12 cells treated with DMSO, CG-428, JWJ-01-375, JWJ-01-377, JWJ-01-378, and entrectinib at the indicated doses for 6 hours. (C) Immunoblot analysis of KM12 cells treated with DMSO, JWJ-01-378 and JWJ-01-392 at the indicated doses for 2 hours. (D) Immunoblot analysis of KM12 cells treated with DMSO, CG-428, JWJ-01-375, JWJ-01-377, JWJ-01-378, and JWJ-01-392 at the indicated doses for 6 hours. (E) Immunoblot analysis of KM12 cells treated with DMSO, 10 nM JWJ-01-378, 10 nM JWJ-01-392 and 10 nM entrectinib for the indicated time-course. (F) Immunoblot analysis of KM12 cells treated with DMSO, 10 nM CG-428, 10 nM JWJ-01-378, and 10 nM JWJ-01-392 for the indicated time-course. (G) Immunoblot analysis of KM12 cells pretreated with 0.5 µM of carfilzomib (Carf), 1 µM MLN4924 (MLN), 0.1 µM entrectinib, 10 µM lenalidomide (Len), 1 µM JWJ-01-392, or 0.1 µM bafilomycin A1 (BafA1) for 2 hours followed by DMSO or 10 nM JWJ-01-378 treatment for 4 hours. Data in (A–G) are representative of n = 3 independent experiments. (H) Protein abundance after treatment of KM12 cells with 100 nM of JWJ-01-378 for 2 hours compared to DMSO. Volcano plots depict fold change abundance relative to DMSO versus P value derived from a moderated t -test. Fold change values and significance designations derived from a moderated t -test are provided in Dataset S1. Data are from n = 3 biologically independent samples.

    Journal: RSC Chemical Biology

    Article Title: Development of PROTACs for targeted degradation of oncogenic TRK fusions

    doi: 10.1039/d6cb00008h

    Figure Lengend Snippet: JWJ-01-378 induces potent degradation of TPM3-TRKA. (A) Immunoblot analysis of KM12 cells treated with DMSO, CG-428, JWJ-01-375, JWJ-01-377, JWJ-01-378, and entrectinib at the indicated doses for 2 hours. (B) Immunoblot analysis of KM12 cells treated with DMSO, CG-428, JWJ-01-375, JWJ-01-377, JWJ-01-378, and entrectinib at the indicated doses for 6 hours. (C) Immunoblot analysis of KM12 cells treated with DMSO, JWJ-01-378 and JWJ-01-392 at the indicated doses for 2 hours. (D) Immunoblot analysis of KM12 cells treated with DMSO, CG-428, JWJ-01-375, JWJ-01-377, JWJ-01-378, and JWJ-01-392 at the indicated doses for 6 hours. (E) Immunoblot analysis of KM12 cells treated with DMSO, 10 nM JWJ-01-378, 10 nM JWJ-01-392 and 10 nM entrectinib for the indicated time-course. (F) Immunoblot analysis of KM12 cells treated with DMSO, 10 nM CG-428, 10 nM JWJ-01-378, and 10 nM JWJ-01-392 for the indicated time-course. (G) Immunoblot analysis of KM12 cells pretreated with 0.5 µM of carfilzomib (Carf), 1 µM MLN4924 (MLN), 0.1 µM entrectinib, 10 µM lenalidomide (Len), 1 µM JWJ-01-392, or 0.1 µM bafilomycin A1 (BafA1) for 2 hours followed by DMSO or 10 nM JWJ-01-378 treatment for 4 hours. Data in (A–G) are representative of n = 3 independent experiments. (H) Protein abundance after treatment of KM12 cells with 100 nM of JWJ-01-378 for 2 hours compared to DMSO. Volcano plots depict fold change abundance relative to DMSO versus P value derived from a moderated t -test. Fold change values and significance designations derived from a moderated t -test are provided in Dataset S1. Data are from n = 3 biologically independent samples.

    Article Snippet: Entrectinib (Selleck Chemicals, #S7998), GNF-8625 (MedChemExpress, #HY-131706A), CG-428 (Tocris, #7425), carfilzomib (MedChemExpress, #HY-10455), MLN4924 (Calbiochem, #5054770001), lenalidomide (Millipore Sigma, #901558), bafilomycin A1 (Cambridge Bioscience, #b0025) and pomalidomide (MedChemExpress, #HY-10984) were purchased from the indicated sources.

    Techniques: Western Blot, Quantitative Proteomics, Derivative Assay