ArticleOncotarget2017
Novel indazole-based small compounds enhance TRAIL-induced apoptosis by inhibiting the MKK7-TIPRL interaction in hepatocellular carcinoma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Expanding Therapeutic Horizons with Indazole-Based Compounds: A Review of Anticancer, Antimicrobial, and Neuroprotective Applications.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026Review
- TIPRL, a Potential Double-edge Molecule to be Targeted and Re-targeted Toward Cancer.Cell biochemistry and biophysics · 2024Review
- Components of the JNK-MAPK pathway play distinct roles in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Article
- TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content.Frontiers in immunology · 2023Article
- Mitogen-activated protein kinase kinase 7 in inflammatory, cancer, and neurological diseases.Frontiers in cell and developmental biology · 2022Review
- Research progress on the relationship between the TOR signaling pathway regulator, epigenetics, and tumor development.Frontiers in genetics · 2022Review
- Hsa_circ_0010235 functions as an oncogenic drive in non-small cell lung cancer by modulating miR-433-3p/TIPRL axis.Cancer cell international · 2021Article
- Knockdown of TOR signaling pathway regulator suppresses cell migration and invasion in non-small cell lung cancer via the regulation of epithelial-to-mesenchymal transition.Experimental and therapeutic medicine · 2020Article
- MKK7, the essential regulator of JNK signaling involved in cancer cell survival: a newly emerging anticancer therapeutic target.Therapeutic advances in medical oncology · 2019Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is one of the most malignant tumors. Although various treatments, such as surgery and chemotherapy, have been developed, a novel alternative therapeutic approach for HCC therapy is urgently needed. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising anti-cancer agent, but many cancer cells are resistant to TRAIL-induced apoptosis. To help overcome TRAIL resistance in HCC cancer cells, we have identified novel chemical compounds that act as TRAIL sensitizers. We first identified the hit compound, TRT-0002, from a chemical library of 6,000 compounds using a previously developed high-throughput enzyme-linked immunosorbent assay (ELISA) screening system, which was based on the interaction of mitogen-activated protein kinase kinase 7 (MKK7) and TOR signaling pathway regulator-like (TIPRL) proteins and a cell viability assay. To increase the efficacy of this TRAIL sensitizer, we synthesized 280 analogs of TRT-0002 and finally identified two lead compounds (TRT-0029 and TRT-0173). Co-treating cultured Huh7 cells with either TRT-0029 or TRT-0173 and TRAIL resulted in TRAIL-induced apoptosis due to the inhibition of the MKK7-TIPRL interaction and subsequent phosphorylation of MKK7 and c-Jun N-terminal kinase (JNK).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.