eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-09-30 19 3 2651 2664 10.13005/bpj/3522 73302 article Murodil Salaydinov 1 Anvar Zaynabiddinov 1 Izzatullo Abdullaev 2 Ulugbek Gayibov 2 Gaybullo Lutpillayev 2 Rakhmatilla Rakhimov 4 Dept. of Human physiology and life safety, Andijan State University, Andijan, Uzbeksitan Dept. of Plantcytoprotectors and Proteins and Peptides, Institute of Bioorganic Chemistry named after A.S.Sadykov, Tashkent, Uzbeksitan Dept. of Human physiology, Namangan State University, Uzbekistan Dept. of Chemistry, Tashkent state transport university, Uzbekistan Calcium dysregulation plays a critical role in vascular dysfunction and the development of cardiovascular diseases. The present study investigated the relaxant activity of KC-4 and its interaction with calcium transport-associated proteins using integrated in vitro and in silico approaches. Vasorelaxant activity was evaluated in isolated rat aortic rings precontracted with 50 mM KCl or 1 μM phenylephrine. The involvement of calcium transport pathways was further assessed using verapamil and phentolamine. Molecular docking studies were performed against major calcium transport proteins, including Ca²⁺-ATPase, SERCA, NCX1, RyR, and voltage-gated calcium channels. KC-4 produced concentration-dependent relaxation of both KCl- and phenylephrine-induced contractions, with IC₅₀ values of 23.15 μM and 18.21 μM, respectively. The greater inhibition of phenylephrine-induced contraction suggests that KC-4 modulates both voltage-dependent and receptor-operated calcium signaling pathways. Comparative experiments with verapamil and phentolamine further supported the involvement of calcium transport mechanisms in the relaxant activity of KC-4. Molecular docking analysis revealed favorable binding affinities of KC-4 toward Ca²⁺-ATPase (−11.7 kcal/mol), L-type calcium channels (−10.8 kcal/mol), SERCA (−10.2 kcal/mol), and R-type calcium channels (−10.2 kcal/mol), whereas weaker interactions were observed with NCX1 and RyR. These findings indicate that KC-4 may regulate vascular smooth muscle contraction through modulation of multiple calcium transport systems. The combined experimental and computational results identify KC-4 as a promising calcium transport-modulating compound with potential relevance for the development of novel agents targeting vascular disorders. https://biomedpharmajournal.org/vol19no3/relaxant-activity-of-kc-4-associated-with-modulation-of-calcium-transport-and-calcium-homeostasis-pathways/ Ca²⁺-ATPase Calcium Homeostasis Calcium Transport Systems In Vitro Pharmacology KCl-Induced Contraction KC-4 Molecular Docking Phenylephrine (PE) Relaxant Activity SERCA Vascular Smooth Muscle (VSM)