ArticleMolecular cancer therapeutics2023
Tinengotinib (TT-00420), a Novel Spectrum-Selective Small-Molecule Kinase Inhibitor, Is Highly Active Against Triple-Negative Breast Cancer.
Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03654547 (A Phase I, First-In-Human, Multicenter, Open-Label Study of TT-00420, Administered Orally in Adult Patients With Advanced Solid Tumors and Triple Negative Breast Cancers), which is not on this map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase I, First-In-Human, Multicenter, Open-Label Study of TT-00420, Administered Orally in Adult Patients With Advanced Solid Tumors and Triple Negative Breast Cancers
Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- The multi-kinase inhibitor tinengotinib as monotherapy or combined with atezolizumab in advanced solid tumors: a phase Ib/II trial.Nature communications · 2026Trial
- Sequencing of Fibroblast Growth Factor Receptor Inhibitors in Cholangiocarcinoma: A Review of Published Cases.JCO precision oncology · 2026Review
- Unravelling Tinengotinib's Mechanistic Landscape in Triple-Negative Breast Cancer Via Network Pharmacology and in Silico Simulation Techniques.Cell biochemistry and biophysics · 2026Article
- Tumor microenvironment and key signaling pathways in breast cancer progression and therapy resistance: A review.Biomolecules & biomedicine · 2026Review
- Decoding the tumor microenvironment of triple-negative breast cancer: from immune evasion to precision immunotherapy.Frontiers in immunology · 2026Review
- Targeting high-risk MYC-overexpressed osteosarcoma with an Aurora kinase inhibitor:--results from a pilot umbrella trial.NPJ precision oncology · 2025Article
- Discovery of a Potent and Highly Selective Inhibitor of Aurora A Kinase.ACS medicinal chemistry letters · 2025Article
- Review
- Aurora kinases signaling in cancer: from molecular perception to targeted therapies.Molecular cancer · 2025Review
- Multiple Kinase Small Molecule Inhibitor Tinengotinib (TT-00420) Alone or With Chemotherapy Inhibit the Growth of SCLC.Cancer science · 2025Article
- Divide and Conquer-Targeted Therapy for Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Targeting the Molecules in EMT: A Potential Therapeutic Opportunity in Breast Cancer.Current molecular medicine · 2025Review
- Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials.Military Medical Research · 2024Review
- Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy.Journal of hematology & oncology · 2024Review
- Targeting FGFR for cancer therapy.Journal of hematology & oncology · 2024Review
- First-In-Human Phase I Study of Tinengotinib (TT-00420), a Multiple Kinase Inhibitor, as a Single Agent in Patients With Advanced Solid Tumors.The oncologist · 2024Article
- Reprogramming the tumor microenvironment - macrophages emerge as key players in breast cancer immunotherapy.Frontiers in immunology · 2024Review
- Therapies targeting triple-negative breast cancer: a perspective on anti-FGFR.Frontiers in oncology · 2024Review
- Therapeutic Potential of Tumor Metabolic Reprogramming in Triple-Negative Breast Cancer.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) is a highly heterogeneous cancer lacking actionable targets. Using a phenotypic screen of TNBC cells, we discovered a novel multiple kinase inhibitor tinengotinib (TT-00420) that strongly inhibited Aurora A/B, FGFR1/2/3, VEGFRs, JAK1/2, and CSF1R in biochemical assays. Exposure to tinengotinib specifically inhibited proliferation across all subtypes of TNBC in vitro and in vivo, while leaving luminal breast cancer cells intact. Incubation of HCC1806 with tinengotinib led to dose-dependent downregulation of genes essential for TNBC cell growth and proliferation. Studies revealed that the potential mechanism of action of tinengotinib involved, predominantly, inhibition of Aurora A or B kinase activity, while inhibition of other pathways contributed to suppression of potency and activity. In vitro treatment of TNBC cell lines or in vivo administration in a syngeneic model with tinengotinib resulted in up-regulation of CXCL10 and 11 or diminished tumor-associated macrophage (TAM) infiltration. Tinengotinib represents a novel combinatorial inhibitory mechanism to treat TNBC. The phase I trial of tinengotinib was completed (ClinicalTrials.gov identifier: NCT03654547).
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.