TRP Channel Inhibitor

GsMTx4 is a spider venom peptide that selectively inhibits cationic-permeable mechanosensitive channels (MSCs) belonging to the Piezo and TRP channel families. GsMTx4 also blocks cation-selective stretch-activated channels (SACs) , attenuates lysophosphatidylcholine (LPC)-induced astrocyte toxicity and microglial reactivity. GsMTx4 is an important pharmacological tool for identifying the role of these excitatory MSCs in normal physiology and pathology.

EIPA (L593754) is an orally active TRPP3 channel inhibitor with an IC₅₀ of 10.5 μM. EIPA also enhances autophagy by inhibiting Na⁺/H⁺-exchanger 3 (NHE3). EIPA inhibits macropinocytosis as well. EIPA can be used in the research of inflammation and cancers, such as gastric cancer, colon carcinoma, pancreatic carcinoma.

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]

Amiloride (MK-870) is an inhibitor of both epithelial sodium channel (ENaC) and urokinase-type plasminogen activator receptor (uTPA). Amiloride is a blocker of polycystin-2 (PC2; TRPP2) channel.

HC-030031 is a potent and selective TRPA1 inhibitor, which antagonizes AITC- and formalin-evoked calcium influx with IC₅₀s of 6.2±0.2 and 5.3±0.2 μM, respectively.

Caffeic acid is an inhibitor of both TRPV1 ion channel and 5-Lipoxygenase (5-LO).

GsMTx4 TFA is a spider venom peptide that selectively inhibits cationic-permeable mechanosensitive channels (MSCs) belonging to the Piezo and TRP channel families. GsMTx4 TFA also blocks cation-selective stretch-activated channels (SACs) , attenuates lysophosphatidylcholine (LPC)-induced astrocyte toxicity and microglial reactivity. GsMTx4 TFA is an important pharmacological tool for identifying the role of these excitatory MSCs in normal physiology and pathology.

ML-SI3 is a mixture of cis/trans ML-SI3 (HY-139426A), which is a TRPML1/2 channel inhibitor with IC₅₀s of 4.7 μM and 1.7 μM, respectively. ML-SI3 also inhibits lysosomal calcium efflux and blocks downstream TRPML1-mediated autophagy. The cis/trans ML-SI3 (HY-139426A) components of ML-SI3 are TRPML2 activators with EC₅₀s of 3.3 μM and 9.4 μM, respectively.

Amiloride hydrochloride (MK-870 hydrochloride) is an inhibitor of both epithelial sodium channel (ENaC) and urokinase-type plasminogen activator receptor (uTPA). Amiloride hydrochloride is a blocker of polycystin-2 (PC2; TRPP2) channel.

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

Eriodictyol ((±)-Huazhongilexone; Dihydroluteolin) is an orally active TRPV1 receptor antagonist (IC₅₀=44-47 nM, rTRPV1) with antioxidant and anti-inflammatory activities. Eriodictyol effectively inhibits lipid peroxidation and the release of proinflammatory cytokines by specifically antagonizing the TRPV1 receptor and activating the Nrf2 signaling pathway. Eriodictyol reduces the levels of ICAM-1, VEGF, eNOS and TNF-α in the retina and maintains the integrity of the blood-retinal barrier. Eriodictyol alleviates oxidative stress-induced apoptosis and hyperalgesia, enhances the activity and cytotoxicity of immune cells (such as B lymphocytes, NK cells and macrophages), and increases the levels of antioxidant enzymes simultaneously. Eriodictyol can be used in the research of diabetic retinopathy, acute lung injury and various pain-related diseases.

EIPA (L593754) hydrochloride is an orally active TRPP3 channel inhibitor with an IC₅₀ of 10.5 μM. EIPA hydrochloride also enhances autophagy by inhibiting Na⁺/H⁺-exchanger 3 (NHE3). EIPA hydrochloride inhibits macropinocytosis as well. EIPA hydrochloride can be used in the research of inflammation and cancers, such as gastric cancer, colon carcinoma, pancreatic carcinoma.

ML-SI1, a racemic mixture of diastereomers, is a TRPML inhibitor with an IC₅₀ value of 15 μM for TRPML1.

(1R,2R)-ML-SI3 is an isomer of ML-SI3 and a potent inhibitor of three isoforms of TRPML. (1R,2R)-ML-SI3 inhibits TRPMLs with IC₅₀s of 1.6 μM (TRPML1), 2.3 μM (TRPML2), and 12.5 μM (TRPML3), respectively.

(E/Z)-BML264 (N-(p-amylcinnamoyl) Anthranilic Acid) is a broad spectrum Phospholipase A₂ (PLA₂) inhibitor and TRP channel blocker. (E/Z)-BML264 is a SLC13A3 inhibitor. (E/Z)-BML264 (N-(p-amylcinnamoyl) Anthranilic Acid) is also an effective reversible inhibitor of calcium-activated chloride channels, has potential to treat arrhythmia.

AMTB hydrochloride is a selective TRPM8 channel blocker. AMTB hydrochloride inhibits icilin-induced TRPM8 channel activation with a pIC₅₀ of 6.23. AMTB hydrochloride can be used for the research of the overactive bladder and painful bladder syndrome. AMTB hydrochloride is a non-selective inhibitor of voltage-gated sodium channels (Na_V).

JNJ-28583113 is an TRPM2 antagonist with brain permeability. JNJ-28583113 inhibits TRPM2 blocked phosphorylation of GSK3α and β subunits. JNJ-28583113 protects cells from oxidative stress induced cell death. JNJ-28583113 also suppresses cytokine release in response to pro-inflammatory stimuli in microglia.

Pico145 (HC-608) is a remarkable inhibitor of TRPC1/4/5 channels, inhibits (-)-englerin A-activated TRPC4/TRPC5 channels, with IC₅₀s of 0.349 and 1.3 nM in cells, and shows no effect on TRPC3, TRPC6, TRPV1, TRPV4, TRPA1, TRPM2, TRPM8.

Pyr3 is a selective inhibitor of transient receptor potential canonical channel 3 (TRPC3), with an IC₅₀ of 700 nM for TRPC3-mediated Ca²⁺ influx.

Primidone is the orally active inhibitor for TRPM3 (IC₅₀ = 0.6 μM), RIP kinase and voltage-gated sodium channel, and the antagonist for GABA receptor. Primidone can be used as the analgesic and anticonvulsant agent.