TRPM8 Antagonist

RQ-00203078 is a highly selective, potent and orally active TRPM8 antagonist with IC₅₀s of 5.3 nM and 8.3 nM for rat and human TRPM8 channels, respectively. RQ-00203078 shows little inhibitory action against TRPV1, TRPA1, TRPV4, or TRPM2 channels.

PF-05105679, a chemical probe, is an orally active and selective TRPM8 antagonist with an IC₅₀ of 103 nM. PF-05105679 has the potential for cold-related pain.

Elismetrep (MT-8554) is a TRPM8 channel antagonist and neuroprotective agent. Elismetrep is used for research on pain, menopause-related vasomotor symptoms, and diabetic peripheral neuropathy.

M8-B is a potent transient receptor potential melastatin-8 (TRPM8) antagonist. M8-B blocks cold-induced and TRPM8-agonist-induced activation TRPM8 channels. M8-B decreases deep body temperature (Tb).

TRPV1 antagonist 3 (Compound 7q) is a potent TRPV1 antagonist with an IC₅₀ of 2.66 nM against capsaicin. TRPV1 antagonist 3 is mode-selective, oral bioavailable (F = 60%) and CNS-penetrant.

TRPV1 antagonist 10 is an orally active and potent TRPV1 antagonist (IC₅₀ = 33.06 nM), moderate to weak URAT1 (IC₅₀ = 22.51 μM) and GLUT9 (60.25% at 50 μM) inhibitor. TRPV1 antagonist 10 has analgesic and urate-lowering effect. TRPV1 antagonist 10 can be studied for research in hyperuricemia and inflammatory pain.

TRPM8 antagonist 4 is a CB2R partial agonist (EC₅₀=54.2 nM, K_i=3.2 μM) and TRPM8 antagonists (IC₅₀=42.3 nM) with high functional selectivity and good physicochemical properties. TRPM8 antagonist 4 has significant anti-inflammatory and analgesic effects and good safety, reduces the mRNA expression of TNF-α, IL-6, and IL-1β.

TRPM8 antagonist 4 prodrug (Compound 8b) is an orally active CB₂R agonist (EC₅₀: 51.2 nM) and a weak TRPM8 antagonist. TRPM8 antagonist 4 prodrug is a prodrug of TRPM8 antagonist 4 (HY-174825). TRPM8 antagonist 4 prodrug exhibits anti-inflammatory and analgesic activities and can be used in the research of inflammation-related pain disorders.

DFL23448 is a selective transient receptor potential melastatin-8 (TRPM8) antagonist. DFL23448 shows IC₅₀ values of 10 and 21 nM in hTRPM8 human embryonic kidney 293 cells activated by Cooling Agent 10 or cold. DFL23448 has limited activity (IC₅₀ >10 μM) at transient receptor potential vanilloids TRPV1, TRPA1, or TRPV4 or at various G protein-coupled receptors. DFL23448 can modify bladder function and reduce bladder overactivity in awake rats.