Abstract: Depression remains a leading cause of disability worldwide, and current treatments are often insufficient—particularly in alleviating cognitive symptoms. HBK-15 is a fast-acting, multimodal compound that has demonstrated robust antidepressant-like and procognitive effects in rodent models. HBK-15 displays functional selectivity across several receptors, including selective activation of ERK1/2 phosphorylation via 5-HT1A, partial stimulation of cAMP signaling through 5-HT7 and D4, and blockade of other pathways such as β-arrestin recruitment.
The compound’s procognitive efficacy was further explored within the Braining project – an international initiative co-funded by the European Union under the Erasmus+ Cooperation Partnership – where HBK-15 reversed pharmacologically induced deficits in cognitive tasks. These findings reinforce the mechanistic hypothesis that functionally selective modulation of serotonergic and dopaminergic signaling may underlie its rapid and broad behavioral effects.
The seminar will highlight both the pharmacological advances in HBK-15 research and the collaborative efforts of the Braining consortium, bringing together partners such as the University of Salamanca and the Jagiellonian University, to investigate novel cognitive models, promote translational research, and strengthen academic collaboration in the field of drug discovery and neuroscience.
Biosketch: Prof. Karolina Pytka is a pharmacologist and head of the Laboratory of Experimental Neuropharmacology at the Jagiellonian University Medical College in Kraków, Poland. She holds degrees in Pharmacy (MSc) and Pharmacology (PhD) from Jagiellonian University and completed postdoctoral training at the University of Strathclyde in Glasgow, United Kingdom.
Her research centers on the discovery and characterization of functionally selective compounds that modulate mood and cognition. She is particularly interested in compounds acting at serotonergic (5-HT1A, 5-HT7) and sigma-1 receptors, especially those that selectively engage specific intracellular signaling pathways involved in emotional and cognitive regulation. By integrating behavioral, molecular, and pharmacological approaches, her team investigates both mechanisms of action and translational relevance.
She is also involved in international collaborations aimed at advancing preclinical neuropsychopharmacology and interdisciplinary training.
Related Publications: Pytka K et al. HBK‑15, a multimodal compound, induces procognitive effects through modulating hippocampal LTP and enhancing theta‑gamma coupling in mice. Preprint, Research Square, 2023. DOI: 10.21203/rs.3.rs-3126208/v1
Sałaciak K, Pytka K. Biased agonism in drug discovery: Is there a future for biased 5-HT1A receptor agonists in the treatment of neuropsychiatric diseases? Pharmacol Ther. 2021; 227:107872. DOI: 10.1016/j.pharmthera.2021.107872
Sniecikowska J et al. Discovery of novel pERK1/2- or β-arrestin-preferring 5-HT1A receptor-biased agonists. J Med Chem. 2020; 63(19):10946–10971. DOI: 10.1021/acs.jmedchem.0c00814
Pytka K et al. Single administration of HBK‑15 reverses depressive-like behaviors in a corticosterone-based mouse model of depression. Mol Neurobiol. 2018; 55(5):3931–3945. DOI: 10.1007/s12035-017-0605-4
Klaudi Lustyk
optionally below is a long version of selected publications related to HBK‑15 and functional selectivity:
Pytka K, Sałaciak K, Lustyk K, Szafarz M, Inteiro-Oliveira S, Diógenes MJ, Xapelli S, Schnur P, Morton LL, Moran EK, Ferreira J, Sakata S, et al. HBK‑15, a multimodal compound, induces procognitive effects through modulating hippocampal LTP and enhancing theta‑gamma coupling in mice. Preprint, Research Square, 2023. DOI: 10.21203/rs.3.rs-3126208/v1
Sałaciak K, Pytka K. Biased agonism in drug discovery: Is there a future for biased 5-HT1A receptor agonists in the treatment of neuropsychiatric diseases? Pharmacol Ther. 2021 Nov;227:107872. DOI: 10.1016/j.pharmthera.2021.107872
Sniecikowska J, Gluch-Lutwin M, Bucki A, Więckowska A, Siwek A, Jastrzębska-Wiesek M, Partyka A, Wilczyńska D, Pytka K, Latacz G, Przejczowska-Pomierny K, Wyska E, Wesołowska A, Pawłowski M, Newman-Tancredi A, Kołaczkowski M. Discovery of novel pERK1/2- or β-arrestin-preferring 5-HT1A receptor-biased agonists: Diversified therapeutic-like versus side effect profile. J Med Chem. 2020 Oct 8;63(19):10946–10971. DOI: 10.1021/acs.jmedchem.0c00814
Pytka K, Głuch-Lutwin M, Kotańska M, Waszkielewicz A, Kij A, Walczak M. Single administration of HBK‑15—a triple 5-HT1A, 5-HT7, and 5-HT3 receptor antagonist—reverses depressive-like behaviors in mouse model of depression induced by corticosterone. Mol Neurobiol. 2018 May;55(5):3931–3945. DOI: 10.1007/s12035-017-0605-4)
📌 Este seminario se enmarca en la iniciativa Braining, una acción colaborativa cofinanciada por la Unión Europea a través del proyecto “Collaborative learning and innovative teaching for brain drug screening” (2023-1-PL01-KA220-HED-000160284), en colaboración con la Unidad de Excelencia iBrains-INCyL.