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Background <p>Breast cancer continues to be a major global health concern, and the need for targeted therapeutic options remains urgent. Janus kinase 1 is an important signalling protein involved in pathways that drive tumour progression. Inhibiting this kinase may provide a promising route to slow or alter disease development. Marine natural compounds contain diverse chemical scaffolds that often exhibit strong bioactivity. This study investigates the South African Natural Compounds Database to identify potential JAK1 inhibitors through a structured computational screening approach.</p> Methods <p>A library of 1,012 marine derived compounds was screened using virtual screening and molecular docking to identify candidates with high affinity toward the JAK1 active region. Cross docking was performed to confirm target preference. Pharmacokinetic and toxicity predictions were generated using ADMET tools. Chemical reactivity was assessed through conceptual DFT calculations. The top hits were evaluated using 200 nanosecond molecular dynamics simulations in order to analyse stability, binding consistency and dynamic behaviour. The PASS server was used to predict potential pharmacological activities of the shortlisted compounds. All computational analyses were performed in parallel with the approved JAK1 inhibitor abrocitinib, which served as a reference standard for comparative evaluation.</p> Results <p>Four compounds showed notable docking scores and favourable interaction profiles. Among them, SANC00125 and SANC00136 demonstrated the highest binding stability during simulations, maintaining consistent interactions within the JAK1 pocket. Both compounds displayed favourable ADMET characteristics, low predicted toxicity, acceptable reactivity profiles and promising PASS predicted antineoplastic activity. These findings indicate strong computational support for predicted JAK1 inhibitory potential.</p> Conclusion <p>The combined computational analysis highlights SANC00125 and SANC00136 as promising putative inhibitors of JAK1. Their stability, predicted safety and potential biological activity support further exploration in laboratory models. These results suggest that marine natural compounds may serve as valuable resources for developing targeted strategies against breast cancer.</p>

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Computational Identification of Potential JAK1 Inhibitors Targeting Breast Cancer: Leveraging the SANC Database for Drug Discovery

  • 期刊论文

  • 发表日期：

    2026年4月7日

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  • Sruthy Sathish,
  • Kalaiarasan Ponnusamy,
  • Thirumurthy Madhavan

摘要

Background

Breast cancer continues to be a major global health concern, and the need for targeted therapeutic options remains urgent. Janus kinase 1 is an important signalling protein involved in pathways that drive tumour progression. Inhibiting this kinase may provide a promising route to slow or alter disease development. Marine natural compounds contain diverse chemical scaffolds that often exhibit strong bioactivity. This study investigates the South African Natural Compounds Database to identify potential JAK1 inhibitors through a structured computational screening approach.

Methods

A library of 1,012 marine derived compounds was screened using virtual screening and molecular docking to identify candidates with high affinity toward the JAK1 active region. Cross docking was performed to confirm target preference. Pharmacokinetic and toxicity predictions were generated using ADMET tools. Chemical reactivity was assessed through conceptual DFT calculations. The top hits were evaluated using 200 nanosecond molecular dynamics simulations in order to analyse stability, binding consistency and dynamic behaviour. The PASS server was used to predict potential pharmacological activities of the shortlisted compounds. All computational analyses were performed in parallel with the approved JAK1 inhibitor abrocitinib, which served as a reference standard for comparative evaluation.

Results

Four compounds showed notable docking scores and favourable interaction profiles. Among them, SANC00125 and SANC00136 demonstrated the highest binding stability during simulations, maintaining consistent interactions within the JAK1 pocket. Both compounds displayed favourable ADMET characteristics, low predicted toxicity, acceptable reactivity profiles and promising PASS predicted antineoplastic activity. These findings indicate strong computational support for predicted JAK1 inhibitory potential.

Conclusion

The combined computational analysis highlights SANC00125 and SANC00136 as promising putative inhibitors of JAK1. Their stability, predicted safety and potential biological activity support further exploration in laboratory models. These results suggest that marine natural compounds may serve as valuable resources for developing targeted strategies against breast cancer.