TRP Channel Inhibitor

JW-65 is a selective TRPC3 channel inhibitor with favorable blood-brain barrier penetration. JW-65 directly binds to human TRPC3 protein and modulates calcium signaling to reduce seizure susceptibility. JW-65 reduces seizure incidence, severity, and duration while prolonging seizure latency in multiple seizure models. JW-65 alleviates Aβ‑induced neuronal damage. JW-65 serves as a valuable tool for research on epilepsy, seizure disorders, and Alzheimer’s disease.

TRPM7-IN-1 (compound SUD), a benzoylurea derivative, is an effective TRPM7 inhibitor. TRPM7-IN-1 induces cell cycle arrest and apoptosis, decreases the migration of MCF-7 and BGC-823 cells. TRPM7-IN-1 decreases vimentin expression and increases E-cadherin expression. TRPM7-IN-1 potentially reduces the TRPM7-like current and decreases TRPM7 expression through the PI3K/Akt signaling pathway. TRPM7-IN-1 is a potential agent to suppress the metastasis of breast and gastric cancer by inhibiting TRPM7 expression and function.

Tivanisiran (SYL1001) is a small interfering RNA (siRNA) targeting TRPV1 . Tivanisiran induces the degradation of TRPV1 mRNA, thereby inhibiting protein synthesis. Tivanisiran alleviates ocular discomfort and pain, and improves ocular hyperemia and tear quality. Tivanisiran is applicable to research related to dry eye disease.

Estradiol 3-methyl ether (EDME) is a highly selective TRPML1 ion channel antagonist and microtubule (microtubule) depolymerizing agent, with IC₅₀ values of 0.22 μM and 3.8 μM against TRPML1 and TRPML2, respectively; it shows no activity against TRPML3. Estradiol 3-methyl ether induces the disruption of cytoplasmic microtubule networks in mammalian cells, with an EC₅₀ of 9 μM. Independent of estrogen receptors, Estradiol 3-methyl ether blocks autophagy (autophagy), TFEB nuclear translocation, and inhibits the migration and invasion of triple-negative breast cancer cells by suppressing TRPML1. Estradiol 3-methyl ether is applicable for relevant research on triple-negative breast cancer.

Piromelatine (Neu-P11) is a melatonin MT₁/MT₂ receptor agonist, serotonin 5-HT_1A/5-HT_1D agonist, and serotonin 5-HT_2B antagonist. Piromelatine (Neu-P11) possesses sleep promoting, analgesic, anti-neurodegenerative, anxiolytic and antidepressant potentials. Piromelatine (Neu-P11) also possesses pain-related P2X3, TRPV1, and Nav1.7 channel-inhibition capacities.

Chrysin 6-C-glucoside 8-C-arabinoside can inhibit the CGRP releasing and the activation of TRPV1 channel. Chrysin 6-C-glucoside 8-C-arabinoside can be used for anti-migraine research.

TRPC5-IN-1 (Compound 6j) is a selective TRPC5 inhibitor with 50.5 % Inhibition for TRPC5 at 3 μM. TRPC5-IN-1 can be used for the research of chronic kidney disease (CKD).

Pinokalant is a broad-spectrum and non-selectivecation channel inhibitor. Pinokalant significantly reduces cortical infarct volume. Pinokalant o improves the metabolic and electrophysiologic status of the ischemic penumbra. Pinokalant reduces lesion size on magnetic resonance images in the acute phase following middle cerebral artery occlusion in rats. Pinokalant has the potential for the research of stroke. Pinokalant also shows anti-SARS-CoV-2 activity.

SKF-96365 is a TRPC channel antagonist and store-operated calcium entry (SOCE) inhibitor. SKF-96365 reduces calcium ion influx by inhibiting the activity and expression of TRPC6, STIM1 and Orai1. SKF-96365 inhibits voltage-gated sodium current (cardiac I_Na/NaV1.5) and slows myocardial conduction. SKF-96365 inhibits phosphorylation/activation of CaMKIIγ and suppresses the downstream AKT signaling pathway. SKF-96365 induces G₂/M phase cell cycle arrest, apoptosis and cytoprotective autophagy in colorectal cancer cells. SKF-96365 alleviates allergic rhinitis symptoms by reducing inflammatory cytokine levels. SKF-96365 reduces intracellular calcium overload, inhibits Homer1 expression, prevents nuclear damage and suppresses apoptosis. SKF-96365 inhibits the growth of colorectal cancer xenografts in nude mice. SKF-96365 is applicable to research related to allergic rhinitis, colorectal cancer, Parkinson's disease, persistent spontaneous nociception and hyperalgesia.

ELP-004 is a TRPC channel inhibitor and inhibtis TRPC channel-mediated Ca²⁺ entry. ELP-004 is an osteoclast inhibitor and inhibits osteoclast differentiation. ELP-004 inhibits basal Ca²⁺ and related NFATc1 translocation in inflammatory osteoclastogenesis. ELP-004 reduces bone erosion in a mouse model of rheumatoid arthritis.

SK2220691 is a potent TRPV4 inhibitor. SK2220691 inhibits pulmonary edema induced by GSK1016790. SK2220691 inhibits HCl-induced increases in key factors such as VEGF, keratinocyte-derived chemokine (KC; CXCL1), and granulocyte colony-stimulating factor (GCSF).

Brophenexin free base (compound 8) is a potent NMDAR/TRPM4 interaction interface inhibitor. Brophenexin free base shows neuroprotective activity. Brophenexin free base prevents NMDA-induced cell death and mitochondrial dysfunction in hippocampal neurons, with an IC₅₀ of 2.1 μM. Brophenexin free base protects mice from MCAO-induced brain damage and NMDA-induced retinal ganglion cell loss.

Oleoyl Serotonin (compound 1e) is a TRPV1 antagonist with IC₅₀ value of 2.57 μM for human TRPV1.

Clemizole is an orally active, blood-brain barrier permeable TRPC5 inhibitor, with an IC₅₀ value of 1.05-1.34 μM against mouse TRPC5. Clemizole blocks TRPC1:TRPC5, TRPC3, TRPC4, TRPC6, TRPC7, hERG, hKCNQ1/hKCNE1 and hKv1.5 channels, and activates TRPA1; it modulates 5HT-2B and HTR2A receptors; it inhibits HCV RNA replication, CrtN enzymatic activity, oxidative stress, neuroinflammation, cell apoptosis and bacterial virulence; it maintains blood-brain barrier (BBB) integrity; it enhances DNA repair capacity; it improves cell viability; and it alters cardiac electrophysiological properties. Clemizole can be used in the research of Dravet syndrome, hepatitis C virus infection, Staphylococcus aureus skin infection, Cisplatin (HY-17394)-induced nephrotoxicity, STXBP1-related diseases, traumatic brain injury and xeroderma pigmentosum type C.

TRPA1-IN-2 (compound 1) is a potent and orally active TRPA1 inhibitor with an IC₅₀ value of 0.04 µM. TRPA1-IN-2 shows anti-inflammation activity.

ProTx-I is a toxin derived from Thrixopelma pruriens and a peptide inhibitor targeting TTX-resistant sodium channels. ProTx-I interacts with voltage sensors of multiple domains such as NaV1.7, reduces neuronal excitability through allosteric modulation of channel gating and alteration of voltage dependence. The IC₅₀ values of ProTx-I against human NaV1.7, NaV1.2, NaV1.6, and NaV1.5 are 95 nM, 104 nM, 21 nM, and 358 nM, respectively; ProTx-I also potently inhibits Ba²⁺ currents of hCav3.1, while its inhibitory potency against hCav3.2 is approximately 160-fold lower. ProTx-I is applicable to the research of chronic pain.

Resolvin D2-d₅ is the deuterium labeled Resolvin D2. Resolvin D2 is a metabolite of docosahexaenoic acid (DHA), with anti-inflammatory, anti-infective activities. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Resolvin D2 is a remarkably potent inhibitor of TRPV1 (IC₅₀ = 0.1 nM) and TRPA1 (IC₅₀ = 2 nM) in primary sensory neurons.

FP802 dihydrochloride is an orally active potent TwinF interface inhibitor that disrupts and detoxifies the NMDAR/TRPM4 death complex. FP802 dihydrochloride exerts powerful neuroprotective effects in the 5xFAD mouse model of Alzheimer’s disease (AD) by preventing cognitive decline, preserving neuronal structural integrity, reducing amyloid-β plaque formation, and mitigating mitochondrial pathology. FP802 dihydrochloride stops loss of motor neurons, reduces serum neurofilament light chain (NfL) levels, improves motor performance, and extends life in a mouse model of amyotrophic lateral sclerosis (ALS). FP802 dihydrochloride can be used for AD and ALS research.

TRPM3-IN-1 (compound 124) is an inhibitor of TRPM3 with an IC₅₀ value <1 µM. TRPM3-IN-1 can be used in the research of pain and inflammatory^[1]

TRPM8-IN-1 (example 14) is an inhibitor of transient receptor potential melastatin-8 (TRPM8) channels, IC₅₀<5 μM.