Targeting growth factors for chronic heart failure: Molecular docking insights of telmisartan compared with sorafenib

References

1. of Telmisartan and Sorafenib toward the Prajapati and Shah / Indian Journal of Pharmacy and Pharmacology 2025;12(3):161�166 165 selected fibrosis-related targets. As shown in (Table 2), Telmisartan demonstrated stronger binding affinities with FGFR1, TGFβ1R, and VEGFR2 compared to Sorafenib, while Sorafenib exhibited greater affinity for PDGFRα and TGFβ2R. These findings suggest that Telmisartan may preferentially modulate receptors associated with fibroblast activation and vascular remodeling, whereas Sorafenib shows a stronger influence on platelet-derived and TGFβ2- mediated signaling. The interaction profiles further highlighted mechanistic differences between the two drugs. Sorafenib predominantly formed multiple conventional hydrogen bonds, such as with ASP, ASN, and LYS residues in FGFR1 (Figure 1a), while Telmisartan interacted largely through van der Waals forces with several hydrophobic residues, complemented by a hydrogen bond with LYS (Figure 1b). This suggests that Sorafenib’s binding stability is strongly hydrogen bond–driven, whereas Telmisartan relies on hydrophobic interactions with selective hydrogen bonding for stabilization. In PDGFRα binding (Figure 2a) and (Figure 2b), Sorafenib displayed a combination of hydrogen bonds (ASP, ARG, and LYS) and van der Waals contacts, which may explain its superior binding affinity. Conversely, Telmisartan engaged extensively with hydrophobic residues, particularly TYR, VAL, and PHE, but lacked multiple stabilizing hydrogen bonds, consistent with its slightly lower binding score. Similar trends were observed in the TGFβ1R complex, where Sorafenib established hydrogen bonds with GLU and LYS residues, alongside van der Waals contacts (Figure 3a), while Telmisartan relied on widespread hydrophobic interactions supplemented with two hydrogen bonds (SER and LYS) (Figure 3b). Interestingly, Telmisartan still demonstrated stronger binding affinity at this receptor, implying that van der Waals interactions played a more dominant stabilizing role. For TGFβ2R (Figure 4a) and (Figure 4b), Sorafenib again formed a greater number of hydrogen bonds with residues such as CYS, ASN, HIS, and VAL, alongside van der Waals contacts, which contributed to its higher binding energy compared to Telmisartan. In contrast, Telmisartan engaged mostly through hydrophobic contacts, with fewer hydrogen bonds, accounting for its slightly weaker affinity. Finally, in the VEGFR2 complex (Figure 5a) and (Figure 5b), Sorafenib displayed interactions with multiple aromatic and polar residues, including hydrogen bonding with key residues such as SER and ASP. However, Telmisartan formed an extensive hydrophobic network with residues like PHE, VAL, and TYR, which stabilized the binding despite fewer hydrogen bonds, resulting in its stronger affinity score. Taken together, these observations suggest that Telmisartan, while not traditionally classified as a multi- kinase inhibitor, exhibits strong and selective binding to critical fibrosis-related growth factor receptors, particularly FGFR1, TGFβ1R, and VEGFR2. Its interaction profile, dominated by van der Waals forces with selective hydrogen bonding, highlights a distinct binding mechanism compared to Sorafenib, which relies more heavily on hydrogen bond stabilization. These results indicate that Telmisartan may offer therapeutic benefits beyond its antihypertensive role by interfering with signaling pathways central to cardiac fibrosis and pathological hypertrophy.
2.  Conclusion Molecular docking analysis indicates that Telmisartan exhibits notable binding affinity to key growth factors involved in cardiac fibrosis and remodeling, comparable to the established growth factor inhibitor, Sorafenib. While Sorafenib demonstrated stronger interactions with PDGFRα and TGFβ2R, Telmisartan exhibited superior affinity for FGFR1, TGFβ1R, and VEGFR2, suggesting its potential role in modulating fibrosis and hypertrophic signaling. These findings provide insights into Telmisartan’s potential repurposing as a growth factor inhibitor in CHF management, warranting further experimental validation.
3.  Declarations
4. Ethics approval and consent to participate Not Applicable
5. Consent for publication Not Applicable
6. Availability of data and material Not Applicable
7. Competing interests Both authors declare no conflict of interest.
8. Funding Not Applicable
9.  Authors Contribution
10. Anil Kumar Prajapati: Designed, conceived, collected data, and wrote the manuscript.
11. Gaurang B. Shah: Supervised the work and reviewed the manuscript
12.  Acknowledgment Normi Gujjar, JRF at L. M. College of Pharmacy, Ahmedabad, Gujarat, India. References
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