Tolvaptan (OPC-41061) is an orally bioavailable, selective, arginine vasopressin receptor 2 (V2, AVPR2) antagonist that can be used to treat hyponatremia.

V2 receptor:3 nM

Tolvaptan降低心脏衰竭犬体内心脏前负荷,而对肾功能,全身血流动力学或循环神经激素没有不利影响.Tolvaptan在人类多囊肾病动物模型中,导致肾脏重量减轻以及囊肿纤维化和体积的减小.Tolvaptan在大鼠模型-急性和慢性低钠血症中,改善低钠血症,起到预防死亡作用.在心力衰竭大鼠中,Tolvaptan明显升高无电解质水清除（E-CH(2)O）,并增加尿精氨酸加压素的排泄.

Tolvaptan在常染色体显性多囊肾病的细胞中,浓度依赖性抑制精氨酸加压素诱导的cAMP产生,IC50为0.1 nM。Tolvaptan抑制AVP诱导的ERK信号传导和细胞增殖。Tolvaptan抑制AVP引起的氯（-）的分泌,并降低在三维胶原基质内培养ADPKD细胞体外生长囊肿。Tolvaptan抑制[（3）H] AVP与人类V（2）受体的结合,其选择性比V（1a）受体高29倍,并且对V（1b）受体没有抑制作用。AVP诱导的HeLa细胞中,Tolvaptan不仅抑制[(3)H〕AVP的结合也抑制环AMP的表达。

Cell-free autophosphorylation assay using time-resolved fluorometry: Neratinib is prepared as 10 mg/mL stocks in DMSO and diluted in 25 mM HEPES (pH 7.5; 0.002 ng/mL-20 μg/mL). Purified recombinant COOH-terminal fragments of HER2 (amino acids 676-1255) or epidermal growth factor receptor (EGFR) (amino acids 645-1186) [diluted in 100 mM HEPES (pH 7.5) and 50% glycerol] is incubated with increasing concentrations of Neratinib in 4 mM HEPES (pH 7.5), 0.4 mM MnCl2, 20 μM sodium vanadate, and 0.2 mM DTT for 15 minutes at room temperature in 96-well ELISA plates. The kinase reaction is initiated by the addition of 40 μM ATP and 20 mM MgCl2 and allowed to proceed for 1 hour at room temperature. Plates are washed, and phosphorylation is detected using Europium-labeled anti-phospho-tyrosine antibodies (15 ng/well). After washing and enhancement steps, signal is detected using a Victor2 fluorescence reader (excitation wavelength 340 nm, emission wavelength 615 nm). The concentration of Neratinib that inhibits receptor phosphorylation by 50% (IC50) is calculated from inhibition curves.