Yeah that's an interesting compound, it's discovered actually in the early 90's in Japan from a soil bacteria and it's compounds which actually the NCI in the US became very, very interested in, Fujisawa who founded [
PharmaDeals ID = 16305] originally let the NCI play with this they put it through their panel of tests and found it to be an extremely interest in HDAC-inhibitor, it's by far the most potent HDAC-inhibitor that's in development, it's a 1000 times more potent than some of the compounds with the big pharma companies and that eventually found its way into the hands of company called Gloucester Pharmaceuticals in the US . It's an interesting compound because it has a number of very important properties extremely potent, it has a very long pharmacodynamic effect so you give a dose to cells and it will continue to acetylate the histone for many days, that's really important because that forces the cell to behave normally or to die. And it also it also is selective with HDAC-inhibitor that are important cancerinflammation, because unfortunately like most biological systems the HDAC story isn't a simple one, there actually there are 18 HDAC's in three classes the two most interesting there are 11 of them, class one is drive cell cycle effects, class two is drive other effects and you really would take the class one, so and FK228 hits all the right things, so you might think yourself its an interesting product it's in the clinic with somebody else, Gloucester pharmaceutical having a Phase IIb trial so that would normally be the end of the story apart from the fact that when god made this compound he didn't make it as a drug he made it for a completely different purpose and I am sure actually, not really sure the science really knows what that purpose is its purity form in a bacteria, but the consequence of that is it's got some really lousy drug like properties, so for example it induces drug resistance mechanisms and it's pumped out by PGP the pump and also we have problems with liver enzymes, number of problems with this compound that if you are starting from a straight forward medchem program in a pharmaceutical company you wouldn't end up with FK228. So when Karus Therapeutics started off you know the biologist where very interested in FK228 because it seem to do things other drugs couldn't do, but it was never going to be something of interest to take forward for us partly because it's in the hands of Gloucester Pharmaceuticals and partly because some of the problems that it had as a drug. So the premise on which Karus Therapeutics was set up was to take the starting point the scaffold if you like for making new drugs series and apply the same kind of rigorous lead optimization you'd apply to it to any other small molecular program to try and eliminate all the bad bits, retain all the good bits and come up with something which would be the best in class HDAC-inhibitor.