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Acute myeloid leukemia (AML) takes center stage as a highly prevalent and aggressive clonal disorder affecting hematological stem cells. FMS-like tyrosine kinase 3 (FLT3) mutations were prevalent in nearly 30% of the AML cases. However, efforts have led to the development of anti-mutant FLT3 drugs, such as midostaurin, gilteritinib, and quizartinib, to improve treatments. Currently, we are exploring the ability of compounds from anti-leukemic plants to be used in AML therapies, focusing on mutant FLT3 inhibition. Employing computational techniques such as drug-likeness assessment, molecular docking, pharmacokinetics properties profiling, molecular dynamics simulations (MDS), and free energy calculations, we identified 43 out of 57 compounds with oral drug potential. Notably, 7 out of 43 compounds, including flavopiridol, sanggenol Q, norwogonin, oblongixanthones A, oblongixanthones B, apigenin, and luteolin exhibited strong binding affinities ranging from −9.0 to −9.8 kcal/mol, surpassing the control drug gilteritinib (−6.3 kcal/mol). Notably, flavopiridol and norwogonin displayed highly favorable pharmacokinetics and low toxicity profiles. MDS confirmed the stability of their binding through parameters such as root mean square deviation, root mean square fluctuation, and radius of gyration (R g) over 100 ns simulations. Flavopiridol and norwogonin emerge as promising candidates for the development of mutant FLT3 inhibitors. Therefore, experimental studies are warranted to validate their therapeutic potential.

Transforming growth factor β1 (TGF‐β) is a cytokine with pleiotropic biological functions. Recently, its signaling pathway has been highlighted for its implicative paradoxical roles in prostate cancer (PCa). Suppressing downstream effects of this pathway by interfering with receptor complex formation through inhibition of the TGF‐β1 leads to its antitumor effects, illuminating the TGF‐β1 as a viable therapeutic target for PCa. Our compound library—established by a literature‐based approach that identified phytochemicals with published evidence against the TGF‐β1—was screened by employing molecular docking, density functional theory (DFT), and molecular dynamic (MD) simulations to identify TGF‐β1 inhibitors. Eight of the 24 phytochemicals docked from our compound library had a good binding affinity (ranging from −11.7 to −10 kcal/mol) to the TGF‐β1 (PDB: 1PY5). The phytochemicals displayed good stability and reactivity as revealed by the DFT analysis and a desirable pharmacokinetic profile. The top four phytochemical complexes with high binding energies maintained stability throughout the 100 ns simulation. Qualitative studies on the drug repurposing attributes of bisindolylmaleimide, flavopiridol, baicalin, and gefitinib as inhibitors of TGF‐β1 are recommended; most importantly, suggest further wet‐lab studies to corroborate these phytochemicals—SB 202190, SB 203580, silymarin, and cryptotanshinone—in TGF‐β1 targeted drug development. [ABSTRACT FROM AUTHOR]