Tolvaptan

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Tolvaptan (OPC-41061) 是一种高效、选择性、竞争性加压素 V2 受体拮抗剂，Ki 为 0.43 nM。

Tolvaptan (OPC-41061) is a highly potent selective, competitive vasopressin V2-receptor antagonist with Ki of 0.43 nM, >200-fold more selective than for V1A-receptors; inhibits cAMP production induced by AVP with no intrinsic agonist activity; clearly produces dose-dependent aquaresis in rats; orally active.(In Vitro):Tolvaptan (0-100 μM; 24-168 h) decreases the growth of HepG2 cells.Tolvaptan (20-100 μM; 24-48 h) induces cell death in HepG2 cells.Tolvaptan (0-100 μM; 24-48 h) affects cell cycle of HepG2 cells.Tolvaptan (0-100 μM; 24-48 h) causes DNA damage and induces apoptosis of HepG2 cells.Tolvaptan (0-100 μM; 24-48 h) decreases cyclins and CDKs, and increases γ-H2AX, PARP cleavage and LC3B-II in HepG2 cells.Tolvaptan (0-100 μM; 4-24 h) induces phosphorylation of JNK, ERK1/2 and p38 in HepG2 cells.Tolvaptan (0-100 μM; 24-28 h) induces autophagy of HepG2 cells.(In Vivo):Tolvaptan (10 mg/kg; p.o. once per day for 22 days) improves cyclophosphamide (CP)-induced nephrotoxicity in rats.

Tolvaptan (0-100 μM; 24-168 h) decreases the growth of HepG2 cells.Tolvaptan (20-100 μM; 24-48 h) induces cell death in HepG2 cells.Tolvaptan (0-100 μM; 24-48 h) affects cell cycle of HepG2 cells.Tolvaptan (0-100 μM; 24-48 h) causes DNA damage and induces apoptosis of HepG2 cells. Tolvaptan (0-100 μM; 24-48 h) decreases cyclins and CDKs, and increases γ-H2AX, PARP cleavage and LC3B-II in HepG2 cells.Tolvaptan (0-100 μM; 4-24 h) induces phosphorylation of JNK, ERK1/2 and p38 in HepG2 cells.Tolvaptan (0-100 μM; 24-28 h) induces autophagy of HepG2 cells. Cell Viability Assay Cell Line:HepG2 cells Concentration:0-100 μM Incubation Time:24, 48, 96 and 168 hours Result:Time- and dose-dependently inhibited HepG2 cells with IC50s of ＞100, 52.2, 33.0 and 27.1 μM at 24, 48, 96 and 168 hours, respectively.Cell Viability Assay Cell Line:HepG2 cells Concentration:20, 40, 60, 80, and 100 μM Incubation Time:24 and 48 hoursResult:Time- and dose-dependently inhibited HepG2 cell growth and caused cell death, with LDH released at a concentration over 40 μM. Caused oxidative DNA damage and increased ROS production with a concentration of 60-100 μM.Cell Cycle Analysis Cell Line:HepG2 cells Concentration:0-100 μM Incubation Time:24 and 48 hours Result:Caused cell cycle arrest at the G2 phase, dose-dependently increased the percentage of G0/G1 phase cells with a concentration of 20-60 μM and increased the percentage of G2/M phase cells with a concentration of 60-100 μM. Western Blot Analysis Cell Line:HepG2 cells Concentration:0-100 μM Incubation Time:24 and 48 hours Result:Dose-dependently decreased cyclin D1, cyclin D3, cyclin B1, CDK1, CDK2, CDK4, and CDK6, and increased γ-H2AX which is a maker of DNA double strand breaks in HepG2 cells. Increased the full length PARP into cleavage situation and induced PARP cleavage.Apoptosis Analysis Cell Line:HepG2 cells Concentration:0-100 μM Incubation Time:24 and 48 hours Result:Induced cell apoptosis with increasing caspase 3/7 activity at a dose over 40 μM.Western Blot Analysis Cell Line:HepG2 cells Concentration:0-100 μM Incubation Time:4 and 24 hours Result:Induced the activation of ERK1/2 and p38 after 4 or 24 h of exposure at a concentration over 60 μM in HepG2 cells.Cell Autophagy Assay Cell Line:HepG2 cells Concentration:0-100 μM Incubation Time:24 and 48 hours Result:Induced cell autophagy with autophagosome formation and an increasing lysosomal turnover rate.

Tolvaptan (10 mg/kg; p.o. once per day for 22 days) improves cyclophosphamide (CP)-induced nephrotoxicity in rats. Animal Model:Male albino rats with cyclophosphamide intraperitoneal injectionDosage:10 mg/kg Administration:Oral gavage; 10 mg/kg once per day; for 22 days Result:Improved the level of urine volume, serum Na+, serum osmolarity, urinary creatinine, free water clearance, serum creatinine, urea, serum K+, blood pressure, urine osmolarity, fractional excretion of sodium and signs of nephrotoxicity in mice. Decreased caspase-3, Bax and pro-inflammatory cytokines, and increased antiapoptotic Bcl-2 in renal tissue of mice.

OPC 41061 | OPC-41061

GPCR/G Protein

Vasopressin Receptor

vasopressinreceptor1a|vasopressinreceptor2

Other Indications

Other Disease

150683-30-0

448.9413

C26H25ClN2O3

>98% (HPLC)

10 mM in DMSO

O=C(NC1=CC=C(C(N2CCC[C@@H](O)C3=CC(Cl)=CC=C32)=O)C(C)=C1)C4=CC=CC=C4C

Benzamide, N-[4-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methyl-

(-20℃)

With Ice Pack

≥ 2 years