HCN Channel

Zatebradine (UL-FS-49 (free base)) is a potent inhibitor of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels with an IC50 values 1.96 ?M.

Zatebradine (UL-FS-49 (free base); UL-FS-49CL (free base)) is a potent inhibitor of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels with an IC50 value of 1.96 ?M.

HCN-IN-1 is a TLR4 inhibitor and modulator of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, specifically targeting HCN2 and HCN4. It effectively inhibits TLR4-mediated signaling, evidenced by reduced alkaline phosphatase activity. HCN-IN-1 modulates HCN2 currents by shifting the voltage-dependent activation to hyperpolarized potentials and slowing activation kinetics, while also blocking currents through HCN4 channels. This compound demonstrates significant analgesic, anti-inflammatory, and anti-anginal properties, making it valuable for research into inflammatory pain, neuropathic pain, heart failure, and related inflammatory conditions.

dMeThPmR is a selective inhibitor of the human nucleoside transporter 1 (hCNT1), exhibiting a potent inhibitory constant (Ki) in the range of 0.3-0.98 μM. While dMeThPmR shows minimal inhibition of hCNT2 (IC50 = 133 μM) and hCNT3 (Ki = 32.7 μM), it effectively protects cells from the cytotoxic effects of nucleoside drugs. This compound is valuable for research on cancer and related therapies, providing insights into nucleoside transport mechanisms and drug interactions.

MeThPmR is a potent and selective inhibitor of the human nucleoside transporter 1 (hCNT1) with a Ki ranging from 0.16 to 0.69 μM. It exhibits minimal inhibitory activity on hCNT2 (IC50 = 360 μM) and hCNT3 (Ki = 4.7 μM). MeThPmR has been demonstrated to provide protection against the cytotoxic effects of nucleoside drugs, making it a valuable tool for cancer research applications.

RO-275 is a potent and selective HCN1 inhibitor, demonstrating IC50 values of 0.046 µM for HCN1, while showing significantly lower activity against HCN2 (14.3 µM), HCN3 (4.6 µM), and HCN4 (13.9 µM). This compound has been shown to effectively rescue impaired working memory, highlighting its potential utility in researching cognitive dysfunction associated with various brain disorders. RO-275 serves as a valuable tool for investigations into HCN1-related pathways and their implications in neurobiology.

HCN2-IN-3 is an orally active inhibitor of HCN2 ion channels. It effectively reduces the activity of HCN2, making it valuable for research into pain mechanisms, tinnitus, and various central nervous system disorders. Additionally, HCN2-IN-3 has potential applications in studies focusing on mental illnesses and mood-related conditions.

HCN2-IN-6 is a selective inhibitor of the HCN2 ion channel, demonstrating an IC50 value of 7 nM. It exhibits minimal inhibition of HCN4, making it a valuable tool for studying HCN2-specific pathways. This reagent is suitable for research into inflammatory diseases and neurological disorders, facilitating the exploration of potential therapeutic strategies targeting these conditions.

pan-HCN-IN-1 is a potent inhibitor of the hyperpolarization-activated and cyclic-nucleotide-gated 1 (HCN1) ion channel, exhibiting an IC50 value of 58 nM. This compound effectively attenuates the voltage sag response and enhances excitatory postsynaptic potential (EPSP) summation in ex vivo rat brain slices. It serves as a valuable tool for investigating the role of HCN1 channels in neuronal excitability and synaptic integration in various research applications.

MS7710 is a potent inhibitor of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. It effectively reduces HCN channel-mediated Ih current, leading to decreased firing frequency and burst activity in dopaminergic neurons within the ventral tegmental area. Research has demonstrated that MS7710 ameliorates deficits in social interaction and cognitive flexibility related to reward processing in mice subjected to chronic social defeat stress. This compound is valuable for studies focusing on major depressive disorder and its underlying mechanisms.

HCN2-IN-4 is an orally active inhibitor of the HCN2 ion channel, which plays a crucial role in neuronal excitability and rhythmic activity. This compound effectively inhibits HCN2 channel activity, making it a valuable tool for investigating its involvement in pain mechanisms, tinnitus, and various central nervous system disorders. Researchers may utilize HCN2-IN-4 to explore therapeutic strategies targeting these conditions.

HCN2-IN-2 is a selective inhibitor of the HCN2 ion channel, characterized by an IC50 of 145 nM. This azaindazole derivative effectively blocks HCN2 channel activity, preventing abnormal firing in peripheral nociceptive neurons. HCN2-IN-2 is suited for research applications focused on pain modulation and the underlying mechanisms of nociceptive signaling.

HCN2-IN-1 is a potent HCN2 inhibitor with an IC50 of 98 nM. This compound selectively targets hyperpolarization-activated cyclic nucleotide-gated channels, making it a valuable tool for investigating central nervous system (CNS) and psychiatric disorders. HCN2-IN-1 can facilitate research into the mechanisms underlying neuronal excitability and potential therapeutic strategies for related conditions.

HCN2 modulator-6 is a potent inhibitor of the HCN2 ion channel, exhibiting an IC50 of 7 nM. This compound effectively suppresses HCN2 channel activity, making it a valuable tool for investigating mechanisms underlying pain, including inflammatory and neuropathic pain. Additionally, HCN2 modulator-6 is applicable in research focused on tinnitus, central nervous system disorders, psychiatric conditions, and mood disorders.

HCN2-IN-5 is a potent HCN2 ion channel inhibitor with an IC50 of 9 nM, exhibiting minimal inhibitory activity on HCN4. This compound is valuable in the study of inflammatory diseases and neurological disorders, providing insights into the modulation of ion channel activity. Its specificity and potency make it a useful tool for elucidating the role of HCN2 in various physiological and pathological processes.

HCN2 modulator-8 is a selective inhibitor of the HCN2 channel, classified as a pyrazolopyridine derivative. It exhibits significant activity in modulating hyperalgesic and sensory signaling pathways, making it valuable for research into pain management, tinnitus, and various central nervous system disorders, including psychiatric and mood disorders.

HCN2 modulator-5 is a selective inhibitor of the HCN2 ion channel. This compound effectively reduces HCN2 channel activity, making it a valuable tool for investigating mechanisms underlying pain, inflammatory conditions, neuropathic pain, and tinnitus. Additionally, HCN2 modulator-5 can contribute to research focused on central nervous system and psychiatric disorders, including mood disorders.