eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-06-16 19 2 72283 article Shakhnoza Bakirova 3 Shahzod Ergashev 2 Sirojiddin Omonturdiyev 3 Izzatullo Abdullaev 1 Ulugbek Gayibov 1 Shakhlokhon Ismailova 4 Department of Plantcytoprotectors, Institute of Bioorganic Chemistry named after A.S.Sadykov, Tashkent, Uzbekistan Department of Terpenoids and Phenolic Compounds Laboratory, Institute of the Chemistry of Plant Substances named after Academician S. Yu. Yunusov, Uzbekistan Departmentof Humanphysiology, National University of Uzbekistan named after Mirzo Ulugbek, Tashkent, Uzbekistan Deparment of Human physiology, Namangan State University, Uzbekistan Intracellular calcium homeostasis plays a crucial role in the regulation of vascular smooth muscle contraction and relaxation. The present study investigated the vasorelaxant activity of ZS 22-12 using isolated rat thoracic aorta and in silico molecular docking analysis of calcium-regulating proteins. ZS 22-12 significantly inhibited both KCl-induced and phenylephrine-induced contractions in a concentration-dependent manner, with IC₅₀ values of 38.23 μM and 43.57 μM, respectively. Comparative studies with verapamil and phentolamine suggested that the vasorelaxant effect of ZS 22-12 is associated with modulation of voltage-dependent and receptor-operated calcium signaling pathways. To clarify the molecular mechanism, docking studies were performed with the Ca²⁺ L-type channel, Ca²⁺ R-type channel, SERCA, ryanodine receptor (RyR), Na⁺/Ca²⁺ exchanger (NCX), and Ca²⁺-ATPase. ZS 22-12 demonstrated stable binding affinities toward all investigated targets through hydrophobic, hydrogen bonding, and electrostatic interactions. Overall, the combined in vitro and in silico results indicate that ZS 22-12 acts as a multitarget modulator of calcium homeostasis in vascular smooth muscle cells and exhibits promising vasorelaxant potential. https://biomedpharmajournal.org/vol19no2/from-molecular-docking-to-vascular-ion-channel-mechanisms-a-multitarget-study-of-zs-22-12/ Calcium channels Molecular docking NCX Ryanodine receptor SERCA Vascular Smooth muscle Vasorelaxant activity ZS 22-12