<![CDATA[Non-Small Cell Lung Cancer (NSCLC) accounts for roughly 85% of all diagnosed lung cancers, making it the dominant clinical subtype of the disease and a leading contributor to cancer mortality worldwide. Two receptor-linked signalling nodes, driven respectively by the epidermal growth factor receptor (EGFR) and the serine/threonine kinase BRAF, sit at the centre of NSCLC pathogenesis; their reciprocal crosstalk sustains downstream MAPK signalling, drives aggressive tumour progression, and underlies clinical resistance to single-target therapy. These observations justify a search for agents capable of engaging both nodes simultaneously. Peronema canescens (locally known as sungkai), a Kalimantan medicinal plant long used in Dayak traditional practice, has attracted growing pharmacological interest for its anticancer properties. This study evaluated the in silico anticancer potential of ten natural compounds isolated from P. canescens leaves alongside five reference/standard compounds against three structurally characterised NSCLC-relevant targets, namely wild-type EGFR (PDB 1M17), the resistance-associated mutated EGFR (PDB 5UG8), and BRAF (PDB 6B8U), using AutoDock Vina. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles were subsequently predicted using the SwissADME platform. The docking results identified Lantadene A, Lantadene B, and Peronemin A3 as the most consistently favourable ligands across all three receptors. Against mutated EGFR specifically, Lantadene B, Lantadene A, and Peronemin A3 achieved binding energies of −9.1, −8.8, and −8.6 kcal mol⁻¹, respectively, while Peronemin A3 additionally displayed the highest interaction similarity to the native ligand (82.35%) of all compounds tested. All three lead compounds also engaged BRAF favourably and exhibited acceptable ADMET and drug-likeness profiles. Collectively, these computational findings position Lantadene A, Lantadene B, and Peronemin A3 as promising dual BRAF-EGFR-directed lead candidates for NSCLC that merit further in vitro and in vivo validation.]]>
