Cyclovirobuxine D

Cyclovirobuxine D (CVB-D) is an alkaloid, and the main active component of the traditional Chinese medicine B. microphylla, that has diverse biological activities. It is an ether-a-go-go related gene (ERG) potassium channel blocker with an IC50 value of 19.7 µM using whole-cell patch-clamp electrophysiology in HEK293 cells expressing the human receptor. IERG blockade is activation-dependent, indicating CVB-D binds to open ERG channels. CVB-D increases the amount and rate of calcium release from intracellular stores in healthy neonatal rat cardiac myocytes and those isolated from adult rats with heart failure in a concentration-dependent manner. It also increases expression of ryanodine receptor 2 (Ryr2) and sarcoplasmic reticulum calcium ATPase 2a (Serca2a) and decreases expression of the sodium-calcium exchanger (Ncx). In vivo, CVB-D (0.5-2.0 mg/kg) reduces mortality and improves cardiac function in a rat model of congestive heart failure. CVB-D pretreatment (1 mg/kg per day for 4 days) inhibits myocardial apoptosis and mitochondrial cytochrome C release induced by doxorubicin (Cay-15007) in mice. CVB-D also induces cellular autophagy and inhibits growth of MCF-7 breast cancer cells and induces mitochondrial apoptosis in MGC803 and MKN26 gastric cancer cells.Formal Name: (3beta,5alpha,16alpha,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol. CAS Number: 860-79-7. Synonyms: CVB-D, NSC 91722. Molecular Formula: C26H46N2O. Formula Weight: 402.7. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMF:PBS (pH 7.2) (1:4): 0.2 mg/ml, DMSO: 0.25 mg/ml, Ethanol: 1 mg/ml. SMILES: C[C@H](NC)[C@@]1([H])[C@H](O)C[C@@]2(C)[C@]3([H])CC[C@@]4([H])C(C)(C)[C@@H](NC)CC[C@]4(C5)[C@]35CC[C@@]21C. InChi Code: InChI=1S/C26H46N2O/c1-16(27-6)21-17(29)14-24(5)19-9-8-18-22(2,3)20(28-7)10-11-25(18)15-26(19,25)13-12-23(21,24)4/h16-21,27-29H,8-15H2,1-7H3/t16-,17+,18-,19-,20-,21-,23+,24-,25+,26-/m0/s1. InChi Key: GMNAPBAUIVITMI-ABNIRSKTSA-N.