D609

D609 is a potassium salt of the tricyclic xanthate with the formula Tricyclo-[5.2.1.0(2,6)]-dec-9-yl-dithiocarbonate.

D609 consists of 8 isomers (4 diastereomers, each having 2 enantiomers). D609 was first synthesized in 1984 by researchers at the German Cancer Research Center (DKFZ).

More than 300 papers have been published on D609, particularly relating to its inhibition of Phosphatidylcholin Specific Phospholipase C (PC-PLC), including its ensuing antiviral effect.

LMV-601

LMV-601 is the potassium salt of the pure enantiomer (-)-(9S)-exo,exo-O-Tricyclo-[5.2.1.0(2,6)]-dec-9-yl-dithiocarbonate.

In 2001 BioSphings AG isolated the exo,exo diastereomer and in 2006, the (-)-exo,exo enantiomer was first synthesized under the name LMV-601.

lmv-601 activity
LMV-601 is contained in D609 at approximately 40%. LMV-601 was shown to be more potent than D609, the exo,exo racemate and the (+)-exo,exo enantiomer.

Name Description
D609 mixture of 4 stereoisomers („exo-exo“, „exo-endo“, „endo-exo“, „ endo-endo“)
BS-609 racemic mixture of pure exo-exo-stereoisomer
LMV-600 (+)-enantiomer
LMV-601 (-)-enantiomer
BioSphings offers LMV-601 with an enantiomeric purity of > 99,6%. Free Worldwide Shipping until August 2016! Place your order here!

PC-PLC – the target of LMV-601

LMV-601 mechanism

LMV-601 inhibits PC-PLC (Phosphatidycholine specific phospholipase C) which is indispensible for activation of transcription factors regulating HSV and HPV gene expression.

see also: LMV-601: Effect on HPV-16 and HPV-18 Infected Human Cervical Carcinoma Cells, Eberhard Amtmann, Friedrich K. Mayer, Hannelore Pink, Waltraud Baader | http://www.abstractsonline.com |

Abstract form “Tricyclodecan-9-yl-xanthogenate (D609) mechanism of actions: A Mini-review of literature“. Rao Muralikrishna Adibhatla, J. F. Hatcher and A. Gusain | Neurochem Res. Apr 2012; 37(4): 671–679.

PC-PLC (66 kDa) hydrolyzes PC to generate phosphocholine and 1,2-diacylglycerol (DAG). While bacterial PC-PLC has been purified, mammalian PC-PLC has not been cloned and its sequence has not been determined, imposing a limitation on identifying D609 actions on the mammalian enzyme. Rabbit polyclonal antibodies raised against the Bacillus cereus PC-PLC showed cross reactivity against mammalian PC-PLC. Suppressing PC-PLC by D609 in presence or absence of basic fibroblast growth factor (bFGF) stopped proliferation and induced differentiation in various cell systems. In vascular endothelia cells PC-PLC involvement in apoptosis and senescence has been demonstrated. PC-PLC expression changed in a cell-cycle dependent manner inversely with cell division cycle 20 homolog (CDC20) and Cdc20 overexpression caused PC-PLC degradation mediated by ubiquitin-proteasome pathway . PC-PLC inhibition by D609 down-regulated human epidermal growth factor receptor 2 (HER2) over-expression on plasma membrane of breast cancer cells. Human epithelial ovarian cancer cells showed activation of PC-PLC and inhibition by D609 reduced the phosphocholine metabolite. PC-PLC expression also regulated CD16 (highly glycosylated transmembrane protein) in NK cells and treatment with D609 caused dramatic decrease in CD16 receptor and PC-PLC expression on the plasma membrane. Actions of D609 attributed to PC-PLC inhibition include suppressing expression of hypoxia-inducible factor 1α (HIF-1α) after stroke, reduced cytokine expression in lipopolysaccharide (LPS)-stimulated macrophages, prevention of tumor necrosis factor-α (TNF-α) or LPS-induced lethal shock in mice, and protection of immature neurons (do not express glutamate receptors) from oxidative glutamate toxicity by uncoupling the cystine/glutamate anti-porter. Studies indicated that inhibition of PC-PLC by D609 enhanced phospholipase D (PLD) activity in UMR-106 osteoblastic cells either due to a compensatory effect or that D609 directly increased PLD activity. A growing body of evidence implicates PC-PLC in metabolism, proliferation, differentiation, senescence and apoptosis in mammalian cells as well as its role in atherosclerosis and somewhat indirectly in stroke models.