Patent ID: 6329148
Filing Date: 2001-12-11
Classification: A61K

Abstract:
A method for enhanced killing of tumor cells, the method comprising:contacting a susceptible tumor cell with a synergistic combination of a death domain receptor ligand; and a diterpenoid triepoxide having the structure: ##STR2##whereinX.sub.1 is OH, .dbd.O; or OR.sup.1 ;X.sub.2 and X.sub.3 are independently OH, OR.sup.1 or H;R.sup.1 is --C(O)--Y--Z, wherein Y is a branched or unbranched C.sub.1 to C.sub.5 alkyl or alkenyl group; and Z is COOR.sup.2, NR.sup.3 R.sup.3, or +NR.sup.4 R.sup.4 R.sup.4, where R.sup.2 is a cation; R.sup.3 and R.sup.3 are independently H or branched or unbranched C.sub.1 to C.sub.6 alkyl, hydroxyalkyl, or alkoxyalkyl, or R.sup.3 and R.sup.3 taken together form a 5- to 7-member heterocyclic ring whose ring atoms are selected from the group consisting of carbon, nitrogen, oxygen and sulfur, wherein the ring atoms include 2 to 6 carbon atoms, or more nitrogen atoms, and optionally one or more oxygen or sulfur atoms, and wherein the ring is unsubstituted or is substituted with one or more groups selected from R.sup.5, OR.sup.5, NR.sup.5 R.sup.6, SR.sup.5, NO.sub.2, CN, C(O)R.sup.5, C(O)NR.sup.5 R.sup.6, and halogen (fluoro, chloro, bromo, or iodo), where R.sup.5 and R.sup.6 are independently hydrogen, lower alkyl or lower alkenyl; and R.sup.4, R.sup.4 and R.sup.4 are independently branched or unbranched C.sub.1 to C.sub.6 alkyl, hydroxyalkyl or alkoxyalkyl;in a combined dosage effective to kill at least about 50% of said tumor cells.