Network pharmacology, molecular docking, and preliminary in vitro evaluation of Ponatinib in cardiac hypertrophy

Q: What is the clinical evidence from this study?

Population: Cardiac hypertrophy. Intervention: Ponatinib vs. High-salt medium without ponatinib (disease control) and normal medium (normal control). Primary outcome: Cell surface area (hypertrophy) and α-smooth muscle actin (α-SMA) levels.

Q: What does this research mean for the field?

Ponatinib attenuates cardiomyocyte hypertrophy through multi-target modulation of growth factor signaling pathways, including MAPK and PI3K-Akt. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Anil Kumar Prajapati; Gaurang B. Shah; Normi D. Gajjar

doi:10.1007/s44395-026-00050-8

October 9, 2026Discover Pharmaceutical SciencesOpen Access

Network pharmacology, molecular docking, and preliminary in vitro evaluation of Ponatinib in cardiac hypertrophy

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Key result

Ponatinib attenuates salt-induced cardiomyocyte hypertrophy in vitro without reducing cell viability.

Why the study?

Cardiac hypertrophy contributes to adverse remodeling and cardiovascular disease progression, and Ponatinib's molecular targets and effects on hypertrophy require investigation.

Does Ponatinib reduce cardiomyocyte hypertrophy in a high-salt-induced H9C2 in vitro model?

Key Points

To identify molecular targets of the tyrosine kinase inhibitor Ponatinib and evaluate its therapeutic potential against cardiac hypertrophy.
Screened Ponatinib and cardiac hypertrophy targets via public databases, constructing protein–protein interaction networks and performing KEGG pathway enrichment analysis.
Conducted active-site molecular docking with AutoDock Vina against target proteins EGFR, MAPK8, MAP3K7, JAK2, and PDGFRB.
Assessed cell viability, cardiomyocyte size, and α-SMA expression in H9C2 (2–1) cells exposed to high-salt-induced hypertrophy.
Molecular docking demonstrated strong binding affinities for Ponatinib across key targets, particularly PDGFRB and JAK2.
Treatment with 0.25 µM Ponatinib significantly reduced cardiomyocyte hypertrophy while preserving cell viability, although no significant reduction in α-SMA levels was observed.

Structured PICO

Does Ponatinib reduce cardiomyocyte hypertrophy in a high-salt-induced H9C2 in vitro model?

P

Population

In vitro and in silico preclinical study evaluating the effects of ponatinib on high-salt-induced cardiac hypertrophy in H9C2 (2-1) rat cardiomyoblast cells.

I

Intervention

Ponatinib (0.05 µM to 1 µM) administered in vitro for 24 to 48 hours

C

Comparator

Disease control group receiving high-salt medium without Ponatinib, and Normal control group receiving standard DMEM without added salt

O

Outcome

Cell viability, cell surface area (hypertrophy), and alpha-smooth muscle actin (α-SMA) levelssurrogate

Ponatinib demonstrated potential anti-hypertrophic effects in vitro through multi-target modulation of growth factor signaling pathways, suggesting a potential repurposing opportunity for cardiac hypertrophy.

Limitations

In silico predictions may not fully capture the complexity of biological systems.
The H9C2 (2-1) cell line does not completely replicate the physiological behavior of primary cardiac fibroblasts or the in vivo cardiac environment.
Mechanistic validation of key signaling pathways (e.g., PDGFR, JAK/STAT) was not performed using techniques such as Western blotting.
The influence of serum-derived factors in the 10% FBS culture medium cannot be completely excluded.
H9C2 (2–1) cell line does not completely replicate the physiological behavior of primary cardiac fibroblasts or the in vivo cardiac environment.
Mechanistic validation of key signaling pathways was not performed using techniques such as Western blotting or gene expression analysis.
Observed reduction in cell size may partially reflect inhibition of cellular proliferation rather than a purely anti-hypertrophic effect.
Influence of serum-derived factors on the observed responses cannot be completely excluded.

Implication

Ponatinib's in vitro effect merits preclinical testing; Level 5 data leave open any role in cardiac remodeling.

Abstract

Cardiac hypertrophy is a key contributor to adverse remodeling and the progression of cardiovascular diseases. Ponatinib, a multi-targeted tyrosine kinase inhibitor approved for oncology, has been shown to inhibit growth factor signaling pathways implicated in hypertrophy. This study aimed to investigate the molecular targets of Ponatinib and evaluate its effects on cardiac hypertrophy. Network pharmacology was used to identify Ponatinib-associated targets and their overlap with cardiac disease-related genes. Protein–protein interaction (PPI) analysis, Gene Ontology (GO) analysis, and KEGG pathway enrichment analysis were performed to identify key pathways. Molecular docking assessed binding affinities with selected targets. In vitro validation was conducted in H9C2 (2–1) cells subjected to high-salt-induced hypertrophy, in which cell viability, cell size, and α-smooth muscle actin (α-SMA) levels were measured. Twenty-four overlapping targets were identified, with EGFR, MAPK8, MAP3K7, JAK2, and PDGFRB as key regulators enriched in MAPK and PI3K-Akt pathways. Docking showed strong binding affinities, particularly with PDGFRB and JAK2. In vitro, Ponatinib (0.25 µM) significantly reduced cardiomyocyte hypertrophy while maintaining cell viability. However, no significant reduction in α-SMA levels was observed. Ponatinib attenuates cardiac hypertrophy through multi-target modulation of growth factor signaling pathways. Further studies are needed to explore its role in cardiac hypertrophy.

Discussion

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Cite This Study

Prajapati et al. (2026) studied Cardiac hypertrophy. Ponatinib vs. High-salt medium without ponatinib (disease control) and normal medium (normal control) was evaluated on Cell surface area (hypertrophy) and α-smooth muscle actin (α-SMA) levels. Ponatinib (0.25 µM) significantly reduced high salt-induced cardiomyocyte hypertrophy in vitro while maintaining cell viability, although no significant reduction in α-SMA levels was observed.

synapsesocial.com/papers/6acae65a082e6266f39bf60c https://doi.org/10.1007/s44395-026-00050-8

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Network pharmacology, molecular docking, and preliminary in vitro evaluation of Ponatinib in cardiac hypertrophy

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Network pharmacology, molecular docking, and preliminary in vitro evaluation of Ponatinib in cardiac hypertrophy

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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