Sphinx Pharmaceuticals Corp. (NASDAQ:SPHX) announcedWednesday that it has filed an investigational new drug (IND)application with FDA to investigate Kynacyte's ability toenhance the efficacy of chemotherapeutic drugs -- includingdoxorubicin and cisplatin -- in treating solid tumors.
The Phase I clinical trials will examine Kynacyte alone or inconjunction with doxorubicin in 20-30 cancer patients with oneof several solid tumors. These patients will have either alreadyfailed previous chemotherapy or will have tumor types notnormally treated with chemotherapy, said W. Bennett Love,Sphinx's director of business development. Sphinx(NASDAQ:SPHX) of Durham, N.C., will also investigate the use ofKynacyte with other chemotherapies, including cisplatin.
Kynacyte is an analog of a sphingolipid, and as such exhibitsthe hydrophobic properties that "make it want to enter cellmembranes," explained Carson Loomis, Sphinx's vice presidentof biomolecular research. Kynacyte inhibits the activity of theintracellular enzyme family of protein kinase Cs (PKC).Laboratory studies on PKC have shown that the enzymesmediate key cellular functions, including cell proliferation andabnormal differentiation. And preclinical studies have shownthat Kynacyte is able to enhance the anti-proliferative effectsof the chemotherapeutic doxorubicin, thus potentiating itsability to suppress tumor growth.
"We don't know exactly how Kynacyte potentiateschemotherapeutic agents, but there are several hypotheses,"Loomis told BioWorld. For one, it's understood that PKCphosphorylates a multiple drug resistance "pump" in the cellmembrane, present normally in cells, which removes toxiccompounds from the cell. This pump is selected for in somecancer cells, which then become multiple-drug resistant.Kynacyte inhibits PKC. "By inhibiting PKC, we could inhibitturning on of the pump and thus prevent the development ofmultiple drug resistance," Loomis said.
It's also known that PKC regulates the action of the DNA repairenzyme topoisomerase II. And topo II acts to patch the damagedone by anti-tumor agents such as cisplatin, which interferedirectly with DNA synthesis. Thus, Kynacyte might increase theefficacy of cisplatin by inhibiting PKC, which would inhibit topoII activity, which would result in a decreased rate of DNArepair.
"Experiments are under way to differentiate between these twohypotheses or to determine if they both play a role," Loomistold BioWorld.
Sphinx's stock was up 38 cents a share on Wednesday to $7.
-- Jennifer Van Brunt Senior Editor
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