KJM429 (MK-056) is a high-affinity ligand for the rat vanilloid receptor rTRPV1 ( K i =30-63 nM) with a unique dual regulatory function. KJM429 acts as a competitive antagonist to inhibit TRPV1 receptor activation induced by Capsaicin ( HY-10448 ), resiniferatoxin, thermal stimulation and weak acid (pH 6.0), and switches to a TRPV1 agonist under strong acid conditions (pH<5.5). KJM429 effectively blocks calcium influx induced by Capsaicin and partial thermal stimulation, and triggers calcium uptake under low pH conditions, with minimal effects on non-TRPV1-mediated calcium signaling. KJM429 can be used for research on the mechanisms of pain-related diseases such as postherpetic neuralgia, diabetic neuropathy, cluster headache, osteoarthritis and pruritus.
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