Neurokinin Receptor Inhibitor

Dazodeunetant (Example 56) is a nitrogen-containing fused ring derivative. Dazodeunetant is an inhibitor of neurokinin (NK). Dazodeunetant has an IC₅₀ 0f 75.99 nM against NK3R in HEK293-NK3 (IP1). Dazodeunetant can be studied in research for menopausal hot flashes.

TACR1-IN-1 is a TACR1 inhibitor. TACR1-IN-1 attenuates Substance P-driven ERK phosphorylation and downstream malignant programs. TACR1-IN-1 reduces PGP9.5-positive tumor innervation in orthotopic PDAC models. TACR1-IN-1 increases antigen presentation and immune chemokine-related transcript expression under Substance P treatment conditions. TACR1-IN-1 reverses Substance P-associated reduction in Gemcitabine (HY-17026) sensitivity. TACR1-IN-1 can be used for research on pancreatic ductal adenocarcinoma.

Netupitant hydrochloride (CID 6451149 hydrochloride) is a blood-brain barrier penetrable, orally active NK1 receptor inhibitor with a K_i of 0.95 nM (CHO cells) against the human receptor. Netupitant hydrochloride antagonizes the effects induced by Substance P, inhibits the maximal response of Substance P with a long-lasting action, and suppresses NK1 agonist-induced behaviors in mice and gerbils. Netupitant hydrochloride reduces the frequency of bladder contractions, prolongs contraction intervals, decreases basal pressure at high doses, and acts on the afferent branch of the micturition reflex. Netupitant hydrochloride can be used in research related to overactive bladder, chemotherapy-induced nausea and vomiting, post-operative nausea and vomiting, anxiety disorders, and depression.