30 June 2025
The Slowpoke 1 (SLO-1) channel is a large-conductance calcium- and voltage-activated potassium channel and a homotetrameric member of the evolutionarily conserved K+ channel family. Activated by cellular depolarization and cytosolic calcium, SLO-1 plays a critical role in regulating cell excitability and neurotransmitter release. First identified in Drosophila melanogaster slowpoke mutants, this channel is notable for its unusually high conductance and phylogenetic conservation across animal species.
In nematodes, SLO-1 modulates both excitatory and inhibitory receptors, influencing nervous system function. In C. elegans, it regulates neurotransmitter release and is expressed in the nerve ring and body wall muscles. Mutations in the slo-1 gene are associated with altered locomotor phenotypes, underscoring its importance in nervous system regulation.
Recent cryo-EM studies have provided structural insights into the insect SLO channel in various conformations and ligand-bound states, offering a foundation for understanding how SLO-1 can be modulated by small molecules.
To advance research into the physiological and structural mechanisms of the SLO-1 channel, we are offering BI-3972, a potent and selective SLO-1 agonist, free of charge to researchers. BI-3972 specifically targets SLO-1, providing a valuable tool for studying the role of this calcium- and voltage-activated potassium channel in neurotransmission, cell excitability, and channel modulation. Researchers will also receive its negative control, BI-4083, and retain full ownership of their results. As part of our commitment to open science, we encourage the publication of findings using BI-3972.
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About BI-3972:
BI-3972 demonstrates in vitro activity against various parasitic nematodes, effectively inhibiting larval development of Haemonchus contortus (EC50 = 621 nM) and Cooperia oncophora (MIC90 = 10 nM), as well as the motility of Dirofilaria immitis microfilarial (EC50 = 28 nM) and L4 stages (EC50 = 0.21 nM) as part of its phenotypic characterization. This small molecule SLO-1 agonist demonstrates standard drug-like permeability and metabolic stability, while showing no significant inhibition in cytochrome P450 assays.
About opnMe:
opnMe.com, the open innovation portal of Boehringer Ingelheim, fosters science and collaboration initiatives in areas of high unmet medical need. With “Molecules to Order”, we share well-characterized tool compounds free of charge with no IP strings attached. With our “opn2EXPERTS” program, we enlist scientific advice on key biologic issues to fuel further drug discovery and deliver novel solutions that benefit unmet patient needs, such as targeting obesity pathogenesis. Our opn2TALENTS PostDoc grant provides an opportunity for high-caliber talents to pitch their scientific ideas with the goal to conduct their research at one of our discovery research sites.