TASP0434299

TASP0434299 (Compound 10) is a radiolabeled ligand for the vasopressin V1b receptor. TASP0434299 exhibits high binding affinity for human and murine V1B receptors, with IC₅₀ values of 0.526 nM and 0.641 nM, respectively, and shows potent antagonistic activity against the human V1B receptor with an IC₅₀ of 0.639 nM. TASP0434299 is a substrate for human and rhesus monkey P-glycoprotein, resulting in low brain uptake in rhesus monkeys. TASP0434299 binds to V1B receptors in rat and monkey pituitary tissues in a saturable and specific manner both in vitro and in vivo. When radiolabeled with tritium or ¹¹C, TASP0434299 serves as a prototype V1B receptor radiotracer to visualize V1B receptor in the pituitary gland of anesthetized monkeys via positron emission tomography^[1][2][3]. In Vitro:TASP0434299 (60 min) potently inhibits the binding of [³H]AVP to cell membranes of 293FT cells expressing human V₁B receptors, with an IC₅₀ of 0.526 nM^[2].
TASP0434299 (60 min) potently inhibits the binding of [³H]AVP to rat anterior pituitary membranes expressing endogenous rat V₁B receptors, with an IC₅₀ of 0.641 nM^[2].
TASP0434299 (30 min) potently antagonizes AVP-induced [Ca²⁺]ᵢ elevation in Chinese hamster ovary K1 cells expressing human V₁B receptors, with an IC₅₀ of 0.639 nM^[2].
TASP0434299 (1 μM) is a substrate of human P-glycoprotein, with an efflux ratio of 27.9 when detected at a concentration of 1 μM in LLC-GA5-COL300 cells^[2].
TASP0434299 (1 μM; co-incubated with [³H]TASP0434299 for 120 min) completely blocks the specific binding of [³H]TASP0434299 to native rat V₁B receptors in rat anterior pituitary slices^[2].
TASP0434299 (1 μM; co-incubated with [³H]TASP0434299 for 120 min) completely blocks the specific binding of [³H]TASP0434299 to native rhesus monkey V₁B receptors in rhesus monkey anterior pituitary slices^[2].
TASP0434299 potently and selectively binds to human V₁B Rs with an IC₅₀ of 0.526 nM, and exhibits no detectable affinity for human V₁A, V₂ or oxytocin receptors^[3].
TASP0434299 potently antagonizes human V₁B R-mediated intracellular calcium mobilization, with an IC₅₀ of 0.639 nM^[3]. In Vivo:[³H]TASP0434299 (0.93 nM/kg; intravenous administration; single dose) binds specifically and saturably to V₁B receptors in the anterior pituitary gland of rats^[2].
¹¹C-TASP0434299 (0.01-10.7 mg/kg; intravenous injection; single administration) binds specifically to endogenous vasopressin V₁B receptors in the pituitary gland of rhesus monkeys^[3].