Vuckovic, Slavica; Vandyke, Kate; Rickards, David A.; McCauley Winter, Padraig; Brown, Simon H. J.; Mitchell, Todd W.; Liu, Jun; Lu, Jun; Askenase, Philip W.; Yuriev, Elizabeth; Capuano, Ben; Ramsland, Paul A.; Hill, Geoffrey R.; Zannettino, Andrew C. W.; Hutchinson, Andrew T. published the artcile< The cationic small molecule GW4869 is cytotoxic to high phosphatidylserine-expressing myeloma cells>, Synthetic Route of 6823-69-4, the main research area is cationic small mol phosphatidylserine express myeloma cell; GW4869; multiple myeloma; phosphatidylserine; small molecule.
Summary : We have discovered that a small cationic mol., GW4869, is cytotoxic to a subset of myeloma cell lines and primary myeloma plasma cells. Biochem. anal. revealed that GW4869 binds to anionic phospholipids such as phosphatidylserine – a lipid normally confined to the intracellular side of the cell membrane. However, interestingly, phosphatidylserine was expressed on the surface of all myeloma cell lines tested (n = 12) and 9/15 primary myeloma samples. Notably, the level of phosphatidylserine expression correlated well with sensitivity to GW4869. Inhibition of cell surface phosphatidylserine exposure with brefeldin A resulted in resistance to GW4869. Finally, GW4869 was shown to delay the growth of phosphatidylserine-high myeloma cells in vivo. To the best of our knowledge, this is the first example of using a small mol. to target phosphatidylserine on malignant cells. This study may provide the rationale for the development of phosphatidylserine-targeting small mols. for the treatment of surface phosphatidylserine-expressing cancers.
British Journal of Haematology published new progress about Antitumor agents. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Synthetic Route of 6823-69-4.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem