ArticleAmerican journal of physiology. Renal physiology2020
Pharmacokinetics and pharmacodynamics of TTI-101, a STAT3 inhibitor that blocks muscle proteolysis in rats with chronic kidney disease.
Article in American journal of physiology. Renal physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Skeletal muscle atrophy in clinical and preclinical models of chronic kidney disease: A systematic review and meta-analysis.Journal of cachexia, sarcopenia and muscle · 2024Pooled it
- Colitis-Associated Colorectal Cancer-STAT3 Inhibition as a Preventive Strategy.International journal of molecular sciences · 2026Article
- APLNR reduction in kidney-muscle crosstalk in renal model recovered by exercise and STAT3 inhibition.Biochemistry and biophysics reports · 2026Article
- Consequences of Peptide Macrocyclization Revealed by Virus-Inspired β-Hairpin Mimetics.ACS chemical biology · 2026Article
- STAT3 Inhibition to Treat Ulcerative Colitis-Associated Colorectal Cancer.International journal of molecular sciences · 2025Article
- STAT3 axis in cancer and cancer stem cells: From oncogenesis to targeted therapies.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- Hemodialysis Intensifies NLRP3 Inflammasome Expression and Oxidative Stress in Patients with Chronic Kidney Disease.International journal of molecular sciences · 2025Article
- Unraveling the role of STAT3 in Cancer Cachexia: pathogenic mechanisms and therapeutic opportunities.Frontiers in endocrinology · 2025Review
- TTI-101 targets STAT3/c-Myc signaling pathway to suppress cervical cancer progression: an integrated experimental and computational analysis.Cancer cell international · 2024Article
- Skeletal Muscle Injury in Chronic Kidney Disease-From Histologic Changes to Molecular Mechanisms and to Novel Therapies.International journal of molecular sciences · 2024Review
- Computational workflow for discovering small molecular binders for shallow binding sites by integrating molecular dynamics simulation, pharmacophore modeling, and machine learning: STAT3 as case study.Journal of computer-aided molecular design · 2023Article
- Chronic kidney disease promotes atrial fibrillation via inflammasome pathway activation.The Journal of clinical investigation · 2023Article
- Therapeutic Potential of a Small-Molecule STAT3 Inhibitor in a Mouse Model of Colitis.Cancers · 2023Article
- Review
- Discovery of new STAT3 inhibitors as anticancer agents using ligand-receptor contact fingerprints and docking-augmented machine learning.RSC advances · 2023Article
- Skeletal Muscle Complications in Chronic Kidney Disease.Current osteoporosis reports · 2022Review
- Changes of Gene Expression Patterns of Muscle Pathophysiology-Related Transcription Factors During Denervated Muscle Atrophy.Frontiers in physiology · 2022Article
- The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy.International journal of molecular sciences · 2021Review
- Cancer Stem Cell-Associated Pathways in the Metabolic Reprogramming of Breast Cancer.International journal of molecular sciences · 2020Review
- Targeting the JAK2/STAT3 Pathway-Can We Compare It to the Two Faces of the God Janus?International journal of molecular sciences · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Loss of muscle proteins increases the morbidity and mortality of patients with chronic kidney disease (CKD), and there are no reliable preventive treatments. We uncovered a STAT3/CCAAT-enhancer-binding protein-δ to myostatin signaling pathway that activates muscle protein degradation in mice with CKD or cancer; we also identified a small-molecule inhibitor of STAT3 (TTI-101) that blocks this pathway. To evaluate TTI-101 as a treatment for CKD-induced cachexia, we measured TTI-101 pharmacokinetics and pharmacodynamics in control and CKD rats that were orally administered TTI-101or its diluent. The following two groups of gavage-fed rats were studied: sham-operated control rats and CKD rats. Plasma was collected serially (0, 0.25, 0.5, 1, 2, 4, 8, and 24 h) following TTI-101 administration (at oral doses of 0, 10, 30, or 100 mg/kg). Plasma levels of TTI-101 were measured by LC-MS/MS, and pharmacokinetic results were analyzed with the PKSolver program. Plasma TTI-101 levels increased linearly with doses; the maximum plasma concentrations and time to maximal plasma levels (~1 h) were similar in sham-operated control rats and CKD rats. Notably, gavage treatment of TTI-101 for 3 days produced TTI-101 muscle levels in sham control rats and CKD rats that were not significantly different. CKD rats that received TTI-101 for 7 days had suppression of activated STAT3 and improved muscle grip strength; there also was a trend for increasing body and muscle weights. TTI-101 was tolerated at doses of 100 mg·kg
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