TRPC5 Inhibitor

ML204 is a potent, selective TRPC4/TRPC5 channel inhibitor, with at least 19-fold selectivity against TRPC6 and no appreciable effect on all other TRP channels, nor on voltage-gated sodium, potassium, or Ca²⁺ channels.

Clemizole hydrochloride is an orally active, blood-brain barrier permeable TRPC5 inhibitor, with an IC₅₀ value of 1.05-1.34 μM against mouse TRPC5. Clemizole hydrochloride 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 hydrochloride 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.

Oxoglaucine (O-Methylatheroline) is a natural product with multiple activities including autophagy activation, anti-inflammation, antibacterial activity, and immunoregulation. Oxoglaucine inhibits the TRPV5/calmodulin/CAMK-II pathway, suppresses TGFβ-induced Smad2 phosphorylation by upregulating Smad7, blocks Ca²⁺ influx, activates autophagy, alleviates apoptosis and inflammation, inhibits ROS production and the expression of fibrosis markers in hepatocytes, and regulates immune cell populations and responses. Oxoglaucine protects against infections caused by Candida albicans and Klebsiella pneumoniae, and exerts effects on adjuvant-induced arthritis. Oxoglaucine can be used in studies related to arthritis, liver fibrosis, bacterial infections, and fungal infections.

ML204 hydrochloride is a novel, potent, selective TRPC4/TRPC5 channel inhibitor, with at least 19-fold selectivity against TRPC6 and no appreciable effect on all other TRP channels, nor on voltage-gated sodium, potassium, or Ca²⁺ channels.

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.

Clemizole-d₄ is the deuterated-labeled Clemizole (HY-30234). 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.

TRPC5-IN-5 (Compound ph8) is a TRPC5 inhibitor (IC₅₀: 1.28 μM). TRPC5-IN-5 can be used for research of neurological diseases and renal diseases.

TRPC4/5-IN-1 is a potent TRP channel 4/5 (TRPC4/5) inhibitor with IC₅₀s of 2.06 μM and 0.54 μM, respectively. TRPC4/5-IN-1 can be used for proteinuric kidney diseases and skin inflammatory diseases research.

TRPC5-IN-6 (Compound 12) is an orally effective transient receptor potential (TRPC5) inhibitor with a IC₅₀ value of 81 nM. TRPC5-IN-6 has good biosafety and low liver and kidney toxicity, and is expected to play an important role in the treatment of chronic kidney disease (CKD).

TRPC4/5-IN-3 (Compound 32) is the orally active inhibitor for transient receptor potential canonical channel 4/5 (TRPC4/5) with IC₅₀ of 3.6 nM and 5.5 nM. TRPC4/5-IN-3 inhibits hERG channel with IC₅₀ of 6.5 µM. TRPC4/5-IN-3 exhibits good metabolic stability in human/rat/mouse liver microsomes. TRPC4/5-IN-3 exhibits antidepressant and anxiolytic activity in mouse models, exhibits good pharmacokinetic characteristics in mouse with an oral bioavailability of 87%.

TRPC5-IN-4 is potent and safe TRPC inhibitor with IC₅₀ value of 14.07 nM and 65 nM for TRPC5 and TRPC4, respectively. TRPC5-IN-4 shows no damage on the cellular component of liver and kidney. TRPC5-IN-4 can be used for the research of chronic kidney disease (CKD).

Clemizole sulfate is an orally active, blood-brain barrier permeable TRPC5 inhibitor, with an IC₅₀ value of 1.05-1.34 μM against mouse TRPC5. Clemizole sulfate 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 sulfate 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.

BD-1063 is a selective σ-1 receptor antagonist with inhibitory activity against TRPC5 and TRPM3. BD-1063 exerts anti-hyperalgesic and anti-allodynic effects by inhibiting sustained calcium influx mediated by TRPC5 and TRPM3, and reverses the effects of Carrageenan (HY-125474). BD-1063 also significantly reduces excessive ethanol self-administration behavior. BD-1063 is widely used in studies on the mechanisms underlying neuropathic pain, inflammatory hyperalgesia, and alcohol abuse and dependence.